Ian Clements Radical Cystectomy for Bladder Cancer Overview

Radical Cystectomy

Contents

Overview.. 3

Arguments against organ preservation in patients with muscle invasive bladder cancer 4

http://www.urotoday.com/images/stories/documents/cury_2011/10.34%20U.%20Studer.pdf  4

A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer 5

Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder 5

Robotic-assisted laparoscopic radical cystectomy: Evaluation of functional and oncological results  6

Predictors of outcome of non-muscle-invasive and muscle-invasive bladder cancer 6

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution. 6

Invasive bladder cancer in the eighties: transurethral resection or cystectomy. 7

Maximizing cure for muscle-invasive bladder cancer: Integration of surgery and chemotherapy  7

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Well Tolerated Among Elderly Patients  7

Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder 8

Early vs delayed radical cystectomy for ‘high-risk’ carcinoma not invading bladder muscle: Delay of cystectomy reduces cancer-specific survival 9

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995–2006. 9

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy?. 9

Perioperative Mortality Is Significantly Greater in Septuagenarian and Octogenarian Patients Treated With Radical Cystectomy for Urothelial Carcinoma of the Bladder  Urology, 02/01/2011. 10

RC Mortality Stats. 10

Hospital volume and 90-day mortality risk after radical cystectomy: A population-based cohort study  10

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy  12

Long-term complications of conduit urinary diversion. 12

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy. 12

Radical TURB for management of muscle invasive disease. 13

Hospital volume and 90-day mortality risk after radical Cystectomy. 13

Cisplatin-Based Induction Regimens Comparable for Invasive Bladder Cancer 14

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology. 15

Take Home Message. 16

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based  17

Radical cystectomy for bladder cancer in the 70+ population: A nation-wide registry analysis of 845 patients  17

See also Memorial Sloan-Kettering Bladder Cancer Nomogram.. 18

Update on muscle-invasive and locally advanced BC.. 18

Disease progression for neo-ad chemotherapy for TCC: Who’s at risk?. 19

Cystectomy, Radical 20

Current Value of Neoadjuvant Chemotherapy Prior to Cystectomy. 24

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer. 24

Use of radical cystectomy for patients with invasive bladder cancer 25

Treatment and outcome in muscle invasive bladder cancer 26

The management of BCG failure in non-muscle-invasive bladder cancer 27

Prevention and management of complications following radical cystectomy for bladder cancer 27

Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy  28

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer 29

Update of the Clinical Guidelines of the European Association of Urology on muscle-invasive and metastatic bladder carcinoma. 29

Beyond the Abstract – Risk factor analysis in a contemporary cystectomy. 30

An analysis of upper urinary tract recurrence following radical cystectomy for bladder cancer 31

Predictive factors and long term carcinogenic results of patients who no longer have residual tumors (stage pT0) on specimens of total cystectomy carried out for cancer of the bladder 31

Outcome of treatment of bladder cancer: A comparison between low-volume hospitals and an oncology centre  32

Survival after cystectomy for invasive bladder cancer 33

External stoma and peristomal complications following radical cystectomy and ileal conduit diversion  34

A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy. 34

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. 35

Urinary diversion and morbidity after radical cystectomy for bladder cancer 35

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort 36

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer 36

Impact of comorbidity on survival of invasive bladder cancer patients, 1996-2007: A Danish population-based cohort study. 37

Robot-assisted radical cystectomy: intermediate survival results at a mean follow-up of 25 months  38

Invasive TCC in the Elderly: Radical cystectomy?. 38

Management of muscle invasive disease. 39

Bladder cancer in the elderly. 40

Complications and Mortality After Radical Cystectomy for Bladder Transitional Cell Cancer 41

Complications Following Radical Cystectomy for Bladder Cancer in the Elderly. 42

A Thorough Pelvic Lymph Node Dissection in Presence of Positive Margins Associated With Better Clinical Outcomes in Radical Cystectomy Patients. 43

Neobladder vs. Ileal Conduit 45

Analysis of Perioperative and Survival Outcome of RC.. 46

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy. 46

A Population Based Assessment of Perioperative Mortality After Cystectomy for Bladder Cancer 49

Twenty-Year Experience of Radical Cystectomy for Bladder Cancer in a Medium-Volume Centre  50

Impact of Treatment Delay in Patients with Bladder Cancer Managed with Partial Cystectomy in Quebec  51

The Risk Factor for Urethral Recurrence after Radical Cystectomy in Patients with Transitional Cell Carcinoma of the Bladder 51

Chemo-surgery yields 92% survival in metastatic TCC‏.. 53

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy. 60

Radical cystectomy in the treatment of bladder cancer always in due time?. 61

Radical cystectomy for bladder cancer: the case for early intervention. 62

Related Articles. 62

Radical cystectomy for bladder cancer: the case for early intervention. 63

Re: [CAFE] metastatic blc/RC‏.. 69

Subject:           Re: cystectomy a guarantee??. 70

Subject:           Re: metastatic blc/RC.. 71

Re: [CAFE] cystectomy a guarantee??‏. 77

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology. 78

Radical cystectomy for T2 bladder cancer with failed chemo. 79

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer 80

Overview

See: Improving Survival for Patients with Muscle Invasive Bladder Cancer Dr Ralph de Vere White: An overview of Chemo, RC & survival + new predictive diagnostic with an excellent presentation of the need to do chemo first, then RC with >10 node removal

http://www.urotoday.com/37/browse_categories/bladder_cancer/aua_ny_2009__improving_survival_for_patients_with_bladder_cancer__multimedia_presentation10052009.html

This states unequivocally that Chemo should precede TURB and RC for maximum survival chance.

22% get urinary infections after RC (see Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer)

A major review is that of Dr Bajorin:

http://www.asco.org/ascov2/MultiMedia/Virtual+Meeting?&vmview=vm_session_presentations_view&confID=55&trackID=3&sessionID=39

Or http://tinyurl.com/dz8f79

There’s also the problem for men of maybe (most?) have erectile disfunction afterwards (“a contemporary questionnaire-based study that reported 13% and 42% potency rate following radical surgery and nerve-sparing cystectomy, respectively”. Vs. “with trimodality treatment …. 75% were considered to have bladders with normal function” [i])

See also: Rapid metastasis to the scrotum and penis following laparoscopic radical cystoprostatectomy

Status of robot-assisted radical cystectomy – good and getting better

Confirmation that removing >10 nodes @ RC is best

The risk of an upper urinary tract recurrence following a radical cystectomy has been reported to be approximately 2 to 8%

According to European guidelines on BC, the favoured treatment of MIBC is RC with urinary diversion. However, it has been shown that only 16-35% of the patients with MIBC undergo cystectomy. Bladder-sparing treatments (TUR, interstitial readiotherapy, and external radiotherapy with or without systemic chemo) can be considered in patients not suitable for major surgery.  .. Patients with metastases can only be treated with palliative intent. Their median survival is only 6 months and can be extended to 14-15 months by systemic ploychemo.[ii] [that perhaps should be polychemo – IC]

It is important to consider trimodality treatment as an alternative to RC, research shows this gives at least equivalent survival whilst preserving the bladder. See my collation on this (RC Alternatives).

There’s another risk factor: 4.4% of RCs have recurrent cancer

The known factors that effect survival for BC RC are:

Age – older have higher mortality and less survival time

Gender – women have a higher mortality and less survival time

Experience of the surgeon – less experienced ones have poorer outcomes

Invasive bladder cancer in the eighties: Transurethral resection or cystectomy?[iii]

Tue, 29 March 2011

Department of Urology, Fundacio Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain.

Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) or transurethral resection (TUR) in our institution.

We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9%). The American Society of Anesthesiology (ASA) score was III or IV in 23 patients (85.1%). Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8%) patients.

Pathological stage of the RC specimen was pT3 in 18 cases (66.7%). Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6%), with an overall survival (OS) of 42.94%, and cancer-specific survival (CSS) of 60.54%. In patients submitted to TUR, clinical stage was T2 in 36 cases (50%). The mean hospital stay was 7 days, with a readmission rate (RR) of 87.5%. OS and CSS was less than 20%.

RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.

Written by:  Faba OR, Palou J, Urdaneta G, Gausa L, Villavicencio H.

Reference: Int Braz J Urol. 2011 Jan-Feb;37(1):49-56. doi: 10.1590/S1677-55382011000700007

PubMed Abstract  PMID: 21385480

Arguments against organ preservation in patients with muscle invasive bladder cancer

http://www.urotoday.com/images/stories/documents/cury_2011/10.34%20U.%20Studer.pdf

A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer[iv]

Wed, 23 March 2011

Department of Radiation, National Cancer Institute, Cairo University, Cairo, Egypt.

Although radical cystectomy is considered to be the primary treatment for muscle-invasive bladder cancer, it is associated with unfavorable outcome. Local recurrence is still a major problem. Survival rates as well as quality of live are far from being satisfactory. Postoperative radiotherapy is considered the standard adjuvant treatment in the NCI-Egypt. This is a prospective randomized study conducted to compare preoperative with postoperative radiotherapy as regard the survival and complication rates.

In the period from May, 2004 to June 2007, 100 eligible patients were included into the study, 50 patients in each treatment arm. Pelvic irradiation was identical in both groups aiming at 50 Gy/25 Fs/5 wk. Radical cystectomy was the standard surgery. Locoregional control, survival rates, and complications rates were compared in both arms.

Patients had a median follow-up period of 32 months (range 0-69 months). Patients had an average age of 54.8 ± 9.5 years with a male/female ratio 3:1. In the present study, transitional cell carcinoma constitutes (51%), while squamous cell carcinoma was reported in 46% of cases. Grades II and III pathology were 81% and 17%, respectively. Pathological stage P(2b) was encountered in 39.5% of the patients followed by P(3)b (33.3%) and P(3)a (14.6%). For the preoperative group, the 3-year overall survival, disease-free survival, locoregional control, and metastases-free survival rates were 53.4%, 47.4%, 89.3%, and 61.5%, respectively. The corresponding figures for the postoperative group were 51.8%, 34.1%, 80.6%, and 55.7% for the postoperative group. None of the patients had serious radiation reactions.

In our study, preoperative radiotherapy was almost equivalent to postoperative radiation therapy as regard OS, DFS, as well as complication rates. Given the recent physical developments in radiation therapy techniques and the biological rationale for treating the pelvis after cystectomy, adjuvant radiotherapy should be re-evaluated world wide. Preoperative radiotherapy may re-emerge as a useful tool for adjuvant treatment.

Written by: El-Monim HA, El-Baradie MM, Younis A, Ragab Y, Labib A, El-Attar I.

Reference: Urol Oncol. 2011 Feb 24. doi: 10.1016/j.urolonc.2011.01.008

PubMed Abstract PMID: 21353794

Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder[v]

Survival analysis of a German multi-centre study after curative treatment of urothelial carcinoma of the bladder

Tue, 22 March 2011

Urologische Klinik, St. Elisabeth Klinikum Straubing , St. Elisabeth-Straße 23, 94315, Straubing, Deutschland.

matthias.may@klinikum-straubing.de

The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients < 75 and >75 years of age (median follow-up was 42 months).

Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed.

The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p< 0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p< 0.001) and CSS (HR=1.27; p=0.018).

An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Written by: May M, Fritsche HM, Gilfrich C, Brookman-May S, Burger M, Otto W, Bolenz C, Trojan L, Herrmann E, Michel MS, Wülfing C, Tiemann A, Müller SC, Ellinger J, Buchner A, Stief CG, Tilki D, Wieland WF, Höfner T, Hohenfellner M, Haferkamp A, Roigas J, Müller O, Bretschneider-Ehrenberg P, Zacharias M, Gunia S, Bastian PJ.

Reference: Urologe A. 2011 Feb 23. doi: 10.1007/s00120-011-2507-9

PubMed Abstract PMID: 21340593

Robotic-assisted laparoscopic radical cystectomy: Evaluation of functional and oncological results[vi]

Monday, 21 March 2011

Departamento de Urología Robótica, Universidad del Saarland, Homburg/ Saar, Alemania.

Radical cystectomy remains the most effective treatment for patients with localized, invasive bladder cancer and recurrent noninvasive disease. We report our experience with 84 consecutive cases of robotic assisted laparoscopic radical cystectomy with regard to perioperative results, pathological outcomes and surgical complications.

A total of 84 consecutive patients (70 male and 14 female) underwent robotic radical cystectomy and urinary diversion at our institution from January 2007 to August 2010 for clinically localized bladder cancer. Outcome measures evaluated included operative variables, hospital recovery, pathological outcomes and complication rate.

Mean age of this cohort was 65.5 years (range 28 to 82). Of the patients 62 underwent ileal conduit diversion, 22 received a neobladder. Mean operating room time for all patients was 261min. (range: 243-618min.) and mean surgical blood loss was 298ml (range: 50-2000ml). 29% of the cases were pT1 or less disease, 38% were pT2, 26% and 7% were pT3 and T4 disease respectively, 15% were node positive. Mean number of lymph nodes removed was 15 (range 1 to 33). In 2 cases (2.4%) there was a positive surgical margin. Mean days to flatus were 2.12, bowel movement 2.87 and discharge home 17.7 (range: 10-33). There were 45 postoperative complications with 11.9% having a major complication (Clavien grade 3 or higher). At a mean followup of 16.7 months 10 patients (11%) had disease recurrence and 2 died of disease.

Our experience with robotic radical cystectomy for the treatment of bladder cancer suggests that in proper hands this procedure provides acceptable surgical and pathological outcomes.

Written by: Treiyer A, Saar M, Kopper B, Kamradt J, Siemer S, Stöckle M.

Reference: Actas Urol Esp. 2011 Mar;35(3):152-157.

PubMed Abstract  PMID: 21345519

Predictors of outcome of non-muscle-invasive and muscle-invasive bladder cancer[vii]

Thursday, 17 March 2011

Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non-muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10-30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non-muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

Written by:  Youssef RF, Lotan Y.

Reference: ScientificWorldJournal. 2011 Feb 14;11:369-81.  doi: 10.1100/tsw.2011.28

PubMed Abstract  PMID: 21336453

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution[viii]

International Braz J Urol, 03/15/2011

Giannarini G et al. – Patients diagnosed with asymptomatic recurrences during the routine follow–up after radical cystectomy (RC) had a slightly higher survival than patients with symptomatic recurrences.

Does intubated uretero-ureterocutaneostomy provide better health-related quality of life than orthotopic neobladder in patients after radical cystectomy for invasive bladder cancer[ix]

International Urology and Nephrology, 03/15/2011

Vakalopoulos I et al. – Patients with uretero–ureterocutaneostomy (UUC) surprisingly presented at least equal quality of life than the presumably less debilitating and more recent orthotopic neobladder (ONB).

Invasive bladder cancer in the eighties: transurethral resection or cystectomy[x]

International Braz J Urol, 03/09/2011

Faba OR et al. – Radical cystectomy (RC) in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with muscle invasive bladder cancer (MIBC) within this age range is a much less morbid procedure, but disease specific survival is lower.

Maximizing cure for muscle-invasive bladder cancer: Integration of surgery and chemotherapy[xi]

Friday, 25 February 2011

Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

The optimal treatment strategy for muscle-invasive bladder cancer remains controversial.

To determine optimal combination of chemotherapy and surgery aimed at preserving survival of patients with locally advanced bladder cancer.

We performed a critical review of the published abstract and presentation literature on combined modality therapy for muscle-invasive bladder cancer. We emphasized articles of the highest scientific level, combining radical cystectomy and perioperative chemotherapy with curative intent to affect overall and disease-specific survival.

Locally invasive, regional, and occult micrometastases at the time of radical cystectomy lead to both distant and local failure, causing bladder cancer deaths. Neoadjuvant and adjuvant chemotherapy regimens have been evaluated, as well as the quality of cystectomy and pelvic lymph node dissection.

Prospective, randomized clinical trials argue strongly for neoadjuvant cisplatin-based chemotherapy followed by high-quality cystectomy performed by an experienced surgeon operating in a high-volume center. Adjuvant chemotherapy after surgery is also effective when therapeutic doses can be given in a timely fashion. Both contribute to improved overall survival; however, many patients receive only one or none of these options, and the barriers to receiving optimal, combined, systemic therapy and surgery remain to be defined. An aging, comorbid, and often unfit population increasingly affected by bladder cancer poses significant challenges in management of individual patients.

Written by:  Feifer AH, Taylor JM, Tarin TV, Herr HW.

Reference: Eur Urol. 2011 Jan 18. doi: 10.1016/j.eururo.2011.01.014

PubMed Abstract  PMID: 21257257

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Well Tolerated Among Elderly Patients[xii]

: Presented at ASCO-GU

By Ed Susman

ORLANDO, Fla — February 22, 2011 — About half of older patients diagnosed with muscle-invasive bladder cancer achieved at least a partial response following neoadjuvant chemotherapy with gemcitabine and cisplatin, researchers
reported here at the 2011 Genitourinary Cancers Symposium (ASCO-GU).

The treatment prior to cystectomy showed that 44.4% of the patients who were initially diagnosed with a tumour stage >T2 were downgraded to pT0 or pT1 after undergoing chemotherapy.

“Neoadjuvant chemotherapy with gemcitabine and cisplatin is feasible and well-tolerated in elderly patients with adequate renal function,” reported Dora Niederseuss-Beke, MD, Barmherzige Brüder Hospital, Vienna, Austria, in her poster presentation on February 18.

“Patients achieving a less than pT2 pathologic stage after chemotherapy remained progression-free at a median follow-up of 17 months,” she added. “Patients with muscle-invasive urothelial cancer greater than pT2 had a median
progress-free survival of 14 months. The median overall survival has not been reached.”

Among the 23 patients who received chemotherapy, no treatment-related febrile neutropenia or deaths occurred, Dr. Niederseuss-Beke observed. The most common grade 3/4 events were thrombopenia (11 patients), neutropenia (6 patients), leucopenia (3 patients), nausea (2 patients), and pulmonary emboli (2 patients). “Due to these grade 4 thromboembolic events, prophylactic anticoagulation during treatment should be considered,” she noted.

The patients, all aged older than 65 years, included 8 women and 15 men. Their median age was 72; 19 were in World Health Organization (WHO) performance status 0 and the others were in performance status 1.

The study was open to patients with muscle-invasive bladder cancer with no prior treatment. The patients were required to have adequate renal functioning defined as a creatinine clearance of >60 mL/min. They were treated with
gemcitabine 1,000 mg/m[^]2[] on days 1, 8, and 15 and cisplatin 70 mg/m[^]2[] on day 2 every 28 days for 3 cycles. Four weeks after completing chemotherapy, the patients’ tumours were reassessed. Radical cystectomy was then performed 6 to 8 weeks after concluding chemotherapy.

In the trial, 21 of the 23 patients were able to finish the chemotherapy regimen and 17 of the patients eventually underwent cystectomy.

Dr. Niederseuss-Beke and colleagues suggested that the gemcitabine plus cisplatin neoadjuvant therapy might be less toxic than standard methotrexate-vinblastine-doxorubicin-cisplatin combination treatment. They also noted that pathologic response appeared lower in this older cohort than in younger patients.

“Further evaluation in a prospective randomised trial is needed,” the researchers suggested.

Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder[xiii]

Thursday, 24 February 2011

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

To revisit whether the perioperative mortality differs between septuagenarian and octogenarian patients and younger patients in a large contemporary population-based cohort. The data from tertiary care centers have suggested that perioperative mortality after radical cystectomy is not considerably different in septuagenarian or octogenarian patients compared with younger patients. However, population-based data have stated otherwise.

From 1988 to 2006, 12 722 radical cystectomies were performed for urothelial carcinoma of the urinary bladder in 17 Surveillance, Epidemiology, and End Results registries. Of those 12 722 patients, 4480 (35.2%) were aged 70-79 years and 1439 (11.3%) were aged ≥80 years. Univariate and multivariate logistic regression models tested the 90-day mortality after radical cystectomy. Covariates consisted of sex, race, year of surgery, Surveillance, Epidemiology, and End Results registry, and histologic grade and stage.

The overall 90-day mortality rate was 4% for the entire population, 2% for patients aged ≤ 69 years, 5.4% for septuagenarian patients, and 9.2% for octogenarian patients. In the multivariate logistic regression analyses, septuagenarian (odds ratio 2.80; P < .001) and octogenarian (odds ratio 5.02; P < .001) age increased the risk of 90-day mortality after radical cystectomy.

In the present population-based analysis, the perioperative mortality after radical cystectomy was three- and fivefold greater in the septuagenarian and octogenarian patients, respectively, which was greater than that in tertiary care centers. This information should be included in informed consent considerations.

Written by:  Liberman D, Lughezzani G, Sun M, Alasker A, Thuret R, Abdollah F, Budaus L, Widmer H, Graefen M, Montorsi F, Shariat SF, Perrotte P, Karakiewicz PI.

Reference: Urology. 2011 Jan 20. doi: 10.1016/j.urology.2010.07.537

PubMed Abstract  PMID: 21256568

Early vs delayed radical cystectomy for ‘high-risk’ carcinoma not invading bladder muscle: Delay of cystectomy reduces cancer-specific survival

Friday, 18 February 2011

Department of Urology, University Medical Center Mainz, Germany.

Study Type – Therapy (case series) Level of Evidence 4.

To analyze the impact of a delayed radical cystectomy (rCx) and clinical variables on cancer-specific survival (CSS) in patients presenting ‘high-risk’ carcinoma not invading bladder muscle (nmiBCA).

Between 1989 and 2006, 278 patients who presented ‘high-risk’ nmiBCA finally underwent rCx in our institution. CSS was correlated with clinical variables such as the number of transurethral resections of the bladder (TURBs), interval between first TURB and rCx, adjuvant therapies, tumour upstaging at rCx, tumour stage and lymph node (LN) status.

The overall 5- and 10-year CSS was 82% and 76%, respectively. Significant correlations were found between the 5-year CSS and categorized number of TURBs (≤ 2 vs >2: 88% vs 71%; P= 0.001), interval between first TURB and rCx (≤ 4 months vs >4 months: 86% vs 77%; P= 0.04), adjuvant therapies (no vs yes: 86% vs 66%; P= 0.001), tumour upstaging at rCx (no vs yes: 89% vs 67%; P < 0.001), tumour stage at rCx (bladder confined vs non-confined: 88% vs 56%; P < 0.001) and LN status (no vs yes: 88% vs 36%; P < 0.001). Multivariate analysis identified categorized number of TURBs (hazard ratio, HR, 0.14; 95% CI, 0.07-0.44; P < 0.001), categorized interval between first TURB and rCx (HR, 3.27; 95% CI, 1.24-8.59; P= 0.017), LN status (HR, 0.13; 95% CI, 0.06-0.26; P < 0.001) and tumour stage at rCx (HR, 0.49; 95% CI, 0.26-0.92; P= 0.03) as independent risk factors for CSS.

Delay of rCx in ‘high-risk’ nmiBCA deteriorates CSS and should be avoided. The number of TURBs and the interval between first TURB and rCx are causative factors for delayed rCx and are independently correlated with CSS.

Written by: Jäger W, Thomas C, Haag S, Hampel C, Salzer A, Thüroff JW, Wiesner C.

Reference: BJU Int. 2011 Jan 18. doi: 10.1111/j.1464-410X.2010.09980.x

PubMed Abstract PMID: 21244611

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995–2006[xiv]

Use of radical surgery in urothelial cell carcinoma (UCC) invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management.

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy?[xv]

Thursday, 17 February 2011

Department of Urology, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea.

To determine whether the number of lymph nodes (LNs) removed during radical cystectomy (RC) and pelvic LN dissection (LND) is associated with patient survival.

Data on 450 patients who underwent RC and standard bilateral pelvic LND for urothelial bladder cancer without receiving neoadjuvant chemotherapy were reviewed. The extent of LND included common iliac artery bifurcation proximally, genitofemoral nerve laterally and the pelvic floor caudally. The impact of the number of LNs removed, analyzed as both continuous and categorical variables, on cancer-specific survival (CSS) and recurrence-free survival (RFS) was analyzed.

The median number of LNs removed was 18 (mean 19.6, range 10-94). Of total 450 patients, 129 (28.7%) had node-positive (N +) disease. For entire patients, the number of LNs removed was not associated with CSS and RFS in the analysis with continuous variable (P = 0.715; P = 0.442, respectively), quartiles (P = 0.924; P = 0.676, respectively), or < 18 versus ≥18 LNs removed (5-year CSS rates: 67.0% vs. 69.4%, P = 0.679; 5-year RFS rates = 59.4% vs. 60.6%, P = 0.725, respectively). Similarly, the number of LNs removed was not associated with CSS and RFS in both N0 and N + patients, and in each T stage. Multivariate analyses showed that T stage and lymphovascular invasion were significant predictors for survival in N0 patients, whereas adjuvant chemotherapy and LN density were predictors for survival in N + patients.

If meticulous LND was performed based on standardized LND template during RC, the number of LNs removed was not associated with patient survival.

Written by: Park J, Kim S, Jeong IG, Song C, Hong JH, Kim CS, Ahn H.

Reference: World J Urol. 2011 Jan 15. doi: 10.1007/s00345-011-0644-9

PubMed Abstract  PMID: 21240505

Perioperative Mortality Is Significantly Greater in Septuagenarian and Octogenarian Patients Treated With Radical Cystectomy for Urothelial Carcinoma of the Bladder[xvi]
Urology, 02/01/2011

Liberman D et al. – In the present population–based analysis, the perioperative mortality after radical cystectomy was three– and fivefold greater in the septuagenarian and octogenarian patients, respectively, which was greater than that in tertiary care centers.

RC Mortality Stats

Hospital volume and 90-day mortality risk after radical cystectomy: A population-based cohort study[xvii]

Tuesday, 11 January 2011

Division of Urology, VA Puget Sound Health Care System, 1660 S. Columbian Way, S-112-GU, Seattle, WA, 98108, USA.

mporter@u.washington.edu

Hospital cystectomy volume has been associated with in-hospital perioperative mortality in previous studies. In this study, we examine the relationship between hospital cystectomy volume and 90-day mortality in a population-based cohort of patients undergoing cystectomy for bladder cancer.

We performed a retrospective cohort study using population from the State of Washington Comprehensive Hospital Abstract Reporting System (CHARS) database. We examined the association between hospital cystectomy volume (categorized into volume tertiles) and cumulative 90-day mortality in patients undergoing cystectomy for bladder cancer. Multivariate regression was used to adjust for patient age, comorbid disease, year of surgery, and gender. Standard errors were clustered by discharge hospital.

We identified 823 patients who underwent cystectomy for bladder cancer at 39 unique hospitals in 2003-2007. The unadjusted cumulative 90-day cumulative mortality was 5.4, 6.9, and 8.4% for patients discharged from hospitals in the high, medium, and low volume tertiles, respectively (P = 0.35). In the multivariate analysis, the patients undergoing cystectomy who were discharged from hospitals in the highest volume tertile had a lower risk of death in the first 90 days postoperatively compared to patients discharged from hospitals in the low volume tertile, though the finding was not statistically significant (OR = 0.68, 95% CI 0.29-1.56).

Ninety-day cumulative mortality after cystectomy for bladder cancer is significant and may be associated with hospital cystectomy volume.

Written by: Porter MP, Gore JL, Wright JL.

Reference: World J Urol. 2010 Dec 5. doi: 10.1007/s00345-010-0626-3

PubMed Abstract PMID: 21132553

By DukeMD (Inspire) Posted 18 May 2010 at 6:24 pm

The mortality statistics for radical cystectomy, as for any procedure or treatment need to be taken into context to be correctly understood.

1) In-hospital mortality rate = 1-2%
2) The 30-day mortality rate = 1-2%
3) The 60-day mortality rate = 2-3%
4) The 90-day mortality rate = 3-5%

So, while a 1-2% rate is true if you are asking about the likelihood of dying within a month of surgery, it does not count those people that have events or complications later in the postoperative course.

In general, in medicine we attribute a death to a major operative procedure if it occurred within 90 days of the procedure. Is this 100% accurate? Heck no! But it does allow for counting late events (infections, heart attacks, strokes, etc…) that may not manifest themselves immediately after a procedure and may be due, in part, to the procedure.

Incidentally, the mortality rates noted above are DRAMATICALLY affected by how healthy a patient is prior to surgery. For example, an average 50 year has a 90-day mortality rate of about 1% whereas a 90 year old has a 90-day mortality rate of about 15%. In other words, what you bring to the table counts for a lot and the healthier you are prior to surgery, the lower the risk of a problem. (This applies to chemo and radiation too, by the way.)

However, another piece of research on supposedly improved RC had a mortality rate of 20% within 3 years for women

Despite bacillus Calmette-Guerin therapy and early radical cystectomy, patients with primary carcinoma in situ had a high rate of disease progression. Response to bacillus Calmette-Guerin was significantly associated with a lower rate of disease progression or early radical cystectomy.

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy[xviii]

A Canadian multicentre experience – Abstract

Tuesday, 25 January 2011  |  John W Robertson

To evaluate data obtained from a large, multi-institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables.

Data were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan-Meier method and Cox regression analysis.

The median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrence-free and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was<=”” p=””>

RC performed at academic centres provides excellent local control of disease and an acceptable clinical outcome with low perioperative mortality in patients who are treated within a universal healthcare system. Smoking, pelvic lymphadenectomy and receipt of adjuvant chemotherapy are independent prognostic factors for survival. Neoadjuvant chemotherapy continues to be under-utilized in Canada.

Long-term complications of conduit urinary diversion[xix]

“We evaluated long-term surgical complications and clinical outcomes in a large group of patients treated with conduit urinary diversion.

We identified 1,057 patients who underwent radical cystectomy with conduit urinary diversion using ileum or colon at our institution from 1980 to 1998 with complete followup information. Patients were followed for long-term clinical outcomes and analyzed for the incidence of diversion specific complications.

“Conduit urinary diversion is associated with a high overall complication rate but a low reoperation rate. Long-term followup of these patients is necessary to closely monitor for potential complications from the urinary diversion that can occur decades later.

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy[xx]

World Journal of Urology, 01/20/2011

” If meticulous lymph nodes dissection (LND) was performed based on standardized LND template during radical cystectomy (RC), the number of LNs removed was not associated with patient survival.

Radical TURB for management of muscle invasive disease[xxi]

” Retrospective studies suggest that some patients with T2 disease who do not undergo cystectomy have long term survival suggesting TURBT alone is adequate. The challenge is to prospectively identify these patients.

This group studied invasive bladder tumors in 4 samples, based upon their depth into the bladder. Among 133 patients, they found progression in 28%, and the presence of TIS was an independent predictor for progression. A sessile tumor was also significant. At 10 years, the cause-specific survival (CSS) was 79.5 %, with 65% bladder retention. Age had a negative impact on overall survival (OS), but not CSS. This might suggest that young patients are candidates, he said. Since 30% will progress, close followup is essential, he concluded.

Treatment of muscle invasive bladder cancer: Evidence from the National Cancer Database, 2003 to 2007[xxii]

40,388 patients 18 to 99 years old diagnosed with muscle invasive (stages II to IV) bladder cancer in 2003 to 2007 from the National Cancer Database. Treatment included cystectomy, neoadjuvant and adjuvant chemotherapy, chemotherapy without surgery and radiation therapy.

“The proportion of patients treated with cystectomy (42.9%) and radiation therapy (16.6%) remained stable with time while the incidence of those who received chemotherapy increased from 27.0% in 2003 to 34.5% in 2007 due to an increase in neoadjuvant chemotherapy and chemotherapy without surgery.

“The cystectomy rate decreased with age and was lower in racial/ethnic minorities (especially black patients), uninsured or Medicaid patients, patients residing in the South and Northeast, and those treated at nonteaching/research hospitals. The partial cystectomy rate decreased and lymphadenectomy extent increased with time.

“The perioperative mortality rate was 2.6% and it was higher at low vs very high volume hospitals (OR 1.71, 95% CI 1.26-2.32).

Hospital volume and 90-day mortality risk after radical Cystectomy[xxiii]

a population-based cohort study
World Journal of Urology, 12/09/2010

Porter MP et al. – Hospital cystectomy volume has been associated with in–hospital perioperative mortality in previous studies. In this study, authors examine the relationship between hospital cystectomy volume and 90–day mortality in a population–based cohort of patients undergoing cystectomy for bladder cancer. Ninety–day cumulative mortality after cystectomy for bladder cancer is significant and may be associated with hospital cystectomy volume. [My emphasis]

Cisplatin-Based Induction Regimens Comparable for Invasive Bladder Cancer[xxiv]

By: DOUG BRUNK, Internal Medicine News Digital Network 12/03/10
Major Finding: A comparison of induction regimens shows that 87% of patients treated with paclitaxel plus cisplatin and 79% of those given 5-FU plus cisplatin were downstaged to T0, Ta, and Tcis.

Data Source: 97 patients with muscle-invading bladder cancer in a randomized multicenter, phase II trial.

Disclosures: The National Cancer Institute funded the study. Dr. Zietman said that he had no financial conflicts to disclose.

SAN DIEGO – Cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil induction regimens are equally effective, and can be combined with radiation and transurethral resection in a bladder-sparing protocol, preliminary results from an ongoing, randomized, phase II trial show.

Both regimens produce significant acute toxicity, yet more than 90% of patients completed induction and more than 80% completed consolidation without deviation, Dr. Anthony L. Zietman reported at the annual meeting of the American Society for Radiation Oncology.

After a median of 3 years, 73% of patients in the paclitaxel/cisplatin arm and 69% in the 5-FU/cisplatin arm were alive with intact bladders. The difference was not statistically significant.

“Adjuvant therapy remains a challenge after both regimens, with low rates of completion,” said Dr. Zietman, professor of radiation oncology at Massachusetts General Hospital and Harvard Medical School, Boston. “This is a problem because many of these patients have occult micrometastatic disease, so we do want nontoxic adjuvant therapy.”

In the RTOG (Radiation Therapy Oncology Group) 0233 study funded by the National Cancer Institute, Dr. Zietman and his associates at 33 institutions enrolled 97 patients with muscle-invading bladder cancer.

All patients underwent a transurethral resection and then were randomized into two chemotherapy arms: paclitaxel (50 mg/m2 weekly) plus cisplatin (15 mg/m2 on 3 days per week), or 5-FU (400 mg/m2 on 3 days per week on alternate weeks) plus the same cisplatin schedule. Patients in both arms also received radiotherapy twice daily to a total of 64.3 Gy, followed by adjuvant cisplatin/gemcitabine/paclitaxel chemotherapy.

Four patients were not eligible to complete the trial, leaving 46 in the paclitaxel/cisplatin arm and 47 in the 5-FU/cisplatin arm. Median follow-up was 3 years. The median age of patients was 66 years, 84% were men, and 95% had T2 disease.

Statistically similar proportions of patients in both arms had grade 2 or 3 toxicity during chemoradiation (70% in the paclitaxel/cisplatin arm and 62% in the 5-FU/cisplatin arm). The proportion with late toxicity reaching grade 3 or higher was also similar between the two groups (6% and 4%, respectively). The only case of grade 4 toxicity occurred in the paclitaxel/cisplatin arm.

“The big problem with the trial is with the adjuvant chemotherapy,” Dr. Zietman said, noting that 86% of patients in the paclitaxel/cisplatin arm and 76% in the 5-FU/cisplatin arm had grade 3 or 4 toxicity during the later adjuvant treatment.

Dr. Zietman, the immediate past president of ASTRO, reported that 98% of patients in the paclitaxel/cisplatin arm completed induction; while 4 had grade 4 toxicity during induction, 11 had grade 4 toxicity during adjuvant therapy. Similarly, 96% of patients in the 5-FU/cisplatin arm completed induction; only 1 had grade 4 toxicity during induction, but 15 had grade 4 toxicity during adjuvant therapy.

The adjuvant cisplatin/gemcitabine/paclitaxel regimen “is standard chemotherapy given to [patients] after a cystectomy, but it really was a struggle to get them through it,” he said. “It didn’t matter which chemotherapy regimen had been used up front. The outback chemotherapy was difficult. It was toxic.”

After induction therapy, 87% of patients in the paclitaxel/cisplatin arm and 79% in the 5-FU/cisplatin arm were downstaged to T0, Ta, and Tcis bladder cancer; the difference was not statistically significant. Complete response was also statistically similar between the two arms (72% and 62%, respectively).

To date, Dr. Zietman concluded, “both regimens produce similarly high rates of tumor response and bladder preservation. I think it leaves you with a choice. Either regimen can be used.”

Dr. Zietman said that he had no financial conflicts to disclose.

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology[1]

Accepted 2 July 2008. published online 21 July 2008.

Background

Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance.

Objective

We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology.

Design, setting, and participants

Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists.

Measurements

All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications.

Results and limitations

Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1–2 in 51% (n=582), and grade 3–5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%.

Conclusions

Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

Take Home Message

Accurate reporting of complications utilizing the 10 reporting criteria and methodology is essential for preoperative counseling, for identifying modifiable risk factors to reduce complication rates, for planning combined modality treatment, for clinical trial design, and for a more accurate assessment of surgical success.

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based[xxv]

Tuesday, 12 October 2010

Cancer Prognostics and Health Outcomes Unit Department of Urology, University of Montreal Health Centre, Montreal, Canada.

Study Type – Therapy (cohort) Level of Evidence 2b.

To examine cancer-specific mortality (CSM) in patients with pT4N(0-3) M(0) urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N(0-3) M(0) , in a population-based cohort treated with radical cystectomy (RC).

RCs were performed in 5625 pT3-T4bN(0-3) M(0) patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006. Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM. Covariates consisted of age, gender, race, lymph node status and SEER registries. All analyses were repeated in 3635 pN(0) patients.

Of 5625 patients, 2043 (36.3%) had pT4aN(0-3) , 248 (4.4%) had pT4bN(0-3) and 3334 had pT3N(0-3) (59.3%) UCUB. The 5-year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN(0-3) vs pT4bN(0-3) vs pT3N(0-3) patients (all log-rank P= 0.008). In multivariable analyses the rate of CSM was 2.3-fold higher in pT4b vs pT3 (P < 0.001), 1.1-fold higher in pT4a vs pT3 (P= 0.002) and 2.0-fold higher in pT4a vs pT4b patients. After restriction to pN(0) stage, pT4b patients had a 2.3-fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1-fold higher rate of CSM than pT4a patients (P < 0.001). The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB. Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.

Written by: Liberman D, Alasker A, Sun M, Ismail S, Lughezzani G, Jeldres C, Budaus L, Thuret R, Shariat SF, Widmer H, Perrotte P, Graefen M, Montorsi F, Karakiewicz PI.

Reference: BJU Int. 2010 Sep 22. doi: 10.1111/j.1464-410X.2010.09590.x

PubMed Abstract PMID: 20860649

Radical cystectomy for bladder cancer in the 70+ population: A nation-wide registry analysis of 845 patients[xxvi]

Thursday, 19 August 2010

Department of Urology and Andrology, Danube Hospital, Vienna, Austria.

To analyze demographics, perioperative mortality and overall survival of radical cystectomy (RC) in patients aged 70+ years in Austria in a nation-wide registry cohort.

All patients > 69 years who underwent RC in public hospitals (covering > 95% of all surgical procedures) in Austria between 1992 and 2004 were analyzed. Data were provided by the Austrian Health Institute (OBIG).

A total of 845 patients aged 70-89 years (mean 74) entered the analysis. The annual number of cystectomies in this age group increased from 27 in 1992 to 79 (+292%) in 2004. The mean length of hospital stay declined from 37.1 days (in 1992) to 27.1 days (in 2004). The 60-day mortality of the entire cohort was 1.5% and increased to 5.2% in patients aged 80+ years. Almost 50% of patients had to be rehospitalized within 30 days. The 5-year overall survival declined from 62% in those aged 70-74 years to 61% in those aged 75-79 years to 46% in the oldest age group (80+ years).

The annual number of cystectomies in patients aged 70+ years increased substantially during the study period. These nation-wide registry data provide insights into the current status of RC in the elderly in Austria and demonstrate that cystectomy in this age cohort can be done with an acceptable perioperative mortality and overall survival.

Written by: Madersbacher S, Bauer W, Willinger M, Wehrberger C, Berger I, Brössner C.

Reference: Urol Int. 2010 Jul 23. doi: 10.1159/000316100

PubMed Abstract PMID: 20664240

[Me: This report confirms earlier info on RC.
I’m not sure whether the 5-yr survival is after allowing for otherwise rate of deaths in each age range (that is, a percentage would die of other things anyway, so maybe the 5-year survival is, in a sense, better than it looks).
It is worrying that half of all patients need rehospitilisation within a month – I would hope that increased experience would reduce this, not just the time spent in hospital.]

See also Memorial Sloan-Kettering Bladder Cancer Nomogram

http://www.mskcc.org/mskcc/html/73854.cfm for RC survival prediction

Update on muscle-invasive and locally advanced BC[xxvii]

“Dr. Fuad Freiha defined this group of patients as having stage T3b-T4, N0-N1, M0 disease.

The options for these patients are radical cystectomy/pelvic lymph node dissection, bladder sparing (radical TURBT + chemotherapy + radiation therapy), neoadjuvant chemotherapy and radical cystectomy/pelvic lymph node dissection, and radical cystectomy/pelvic lymph node dissection followed by adjuvant chemotherapy. [Or, as in my case, nothing; or ‘watchful waiting]

” ..radical cystectomy/pelvic lymph node dissection (with or without chemotherapy) is still the standard of care for these patients.

” [for] ..patients who refuse such surgical approach. The technique of bladder preservation has evolved over the years to include radical TURBT, external beam radiation therapy, and chemotherapy. This approach, however, is labor intensive and proper patient selection is key for its success.

[Research into chemo before or after RC gives conflicting results]:

“A review and meta-analysis studied the 16 neoadjuvant studies involving 3315 patients that showed a survival benefit of 6.5% for patients treated with neoadjuvant chemotherapy (Winquist et al. J Urol 2004).

“The 6 randomized adjuvant chemotherapy studies showed a significantly longer time to progression and significant prevention of recurrence. Two of the studies showed a survival advantage, with most of the studies being underpowered to show a significant survival benefit.

“A randomized study by Millikan et al. (J Clin Oncol, 2001) compared neoadjuvant with adjuvant cisplatin-based chemotherapy and did not find any survival difference.

“Dr. Freiha concluded that if clinical staging after TURBT shows nodal involvement or extravesical disease, then neoadjuvant chemotherapy should be given, and in the absence of these features, adjuvant chemotherapy should be given to patients with pT3b-T4 or pN+ patients after undergoing radical cystectomy and extended pelvic lymph node dissection.

“In addition, if resectable nodal disease is encountered during cystectomy, cystectomy and lymph node dissection should be completed with plans to administer postoperative chemotherapy.

Disease progression for neo-ad chemotherapy for TCC: Who’s at risk?[xxviii]

Written by David P. Wood, MD

Tuesday, 01 June 2010

SAN FRANCISCO, CA USA (UroToday.com) – Neoadjuvant methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy has previously been combined with radical cystectomy to improve survival from occult metastatic disease. Gemcitabine and Cisplastin (GC) chemotherapy is effective in metastatic bladder cancer and better tolerated. The purpose of this study was to evaluate disease progression while undergoing neoadjuvant GC in muscle-invasive TCC and identify the high risk groups. 74 patients (49 male 25 female) were administered 3-4 intravenous doses of GC at 28 day intervals. Mean age was 68 years (50-78). Group 1 had T2 muscle-invasive disease (n=38), group 2 had T2 + cis (n=29) and group 3 T3 (n=7). CT scans were repeated following chemotherapy. All 74 patients subsequently underwent radical cystectomy with lymph-node dissection and ileal conduit formation (68) or neo-bladder reconstruction (6). Median time interval between initiation of chemotherapy and surgery was19 weeks (average 14-26 weeks). The results are seen in the table below:

Group 1(T2 only) Group 2 (T2+CIS) Group 3 (T3)

Progression           10%                      24%                             57%

Regression             76%                     21%                             14%

No Change             14%                     55%                             28%

The authors conclude that there is an increased risk of development of disease progression in groups 2 (T2+CIS) and group3 (T3) while undergoing neo-adjuvant chemotherapy. Response rates to T2 disease alone are good i.e. in excess of 70%. Further studies with greater numbers of patients and survival data are required.

Cystectomy, Radical[xxix]

Author: Michael Christopher Large, MD, Resident Physician, Department of Urology, University of Chicago Hospitals
Coauthor(s): Scott E Eggener, MD, Assistant Professor of Surgery/Urology, University of Chicago Hospitals

Introduction

In the United States, bladder cancer is the fifth most common cancer (following lung, colon, prostate, and breast cancers), fourth in prevalence among men and eighth among women. More than 90% of bladder cancers are transitional cell in origin, while, in countries with high endemic schistosomiasis rates (eg, Egypt), squamous cell carcinoma (SCC) of the bladder is more common.

Lesions limited to the urothelium (pCIS), mucosa (pTa), or lamina propria (pT1) represent 70%-80% of all newly diagnosed bladder cancer cases. Although prone to recurrences and, less commonly, progression to higher-stage disease, these lesions are typically managed with transurethral resection and selectively with intravesical chemotherapy, such as bacille Calmette-Guérin (BCG), mitomycin, or thiotepa. Patients with pT1 disease, particularly those with high-risk features (eg, multifocality, recurrence after intravesical therapy, extensive lamina propria invasion, concomitant carcinoma in situ [CIS]) are at considerable risk of disease progression and may benefit from early radical cystoprostatectomy.

Muscle-invasive bladder cancer, defined as tumors that invade the muscularis propria (pT2 or higher), requires more intensive therapy. To date, surgical resection via radical cystoprostatectomy (bladder and prostate) and pelvic lymph node dissection remain the criterion standard for determining accurate pathologic staging, optimizing curative potential, and minimizing the risk of tumor recurrence.

History of the Procedure

The first record of a radical cystectomy dates to the late 1800s. In 1949, Marshall and Whitmore described the basic surgical principles of radical cystoprostatectomy. In 1987, following the neuroanatomic mapping of the pelvic plexus by Schlegel and Walsh, nerve-sparing cystectomy became a surgical option that allowed for preservation of sexual function.¹

For many years, radical cystectomy carried a significant perioperative mortality rate (5%-10%). However, presumably because of improvements in surgical technique, the evolution of intensive care medicine, and the availability of new antibiotics, radical cystectomy is now a common procedure in major medical centers and carries a perioperative mortality rate of approximately 1%-2%.² At high-volume centers with postoperative pathway care programs, an ICU stay is no longer routine and the median hospital stay is approximately 7 days.

Problem

Bladder cancer can be axiomatically subdivided into non–muscle invasive and muscle-invasive disease. This article focuses primarily on the management of muscle-invasive transitional cell carcinoma (TCC) and the role of radical cystectomy. For a more in-depth review of the management of non–muscle invasive bladder cancer, see Bladder Cancer.

Frequency

United States

• More than 90% of bladder cancers are TCC.
• Bladder cancer diagnoses increased by 36% from 1984-1993.
• In the United States, up to 600,000 people have bladder cancer. In 2008, an estimated 68,000 new cases of bladder cancer were diagnosed, and 14,000 persons died of the disease.³
• In 2008, the male-to-female incidence ratio was 2.9:1, and the male-to-female mortality ratio is 2.4:1.³
• Bladder cancer is more common in whites than in African Americans.
• The average age at diagnosis is 65 years.
• Screening of asymptomatic individuals is not currently recommended.

International

• In 1996, an estimated 310,000 new cases of bladder cancer were diagnosed worldwide.
• The incidence rate in Western Europe and North America is higher than in East Asian countries.
• In developing countries, many bladder cancers are SCCs caused by the parasite Schistosoma haematobium. In high-prevalence regions, SCC of the bladder has enormous health implications (eg, SCC is the most common solid tumor in Egyptian men).

Etiology

Environmental risk factors

• Tobacco use accounts for up to 50% of all bladder cancer cases; people who smoke heavily quintuple their risk. Former smokers are at less of a risk for the disease than active smokers. The risk associated with second-hand smoke is unclear.
• Exposure to aromatic amines found in some dyes, paints, solvents, leather dust, inks, combustion products, rubbers, and textiles is a risk factor.
• Prior radiation therapy is a risk factor. Women who have undergone pelvic radiation (eg, for cervical cancer) have a 2- to 4-fold increased incidence rate; survival rates are poorer in men who have undergone radiation for prostate cancer than in men of similar age and stage who have not undergone radiation.⁴
• Treatment with cyclophosphamide (Cytoxan, Neosar) and ifosfamide (Ifex) may lead to the development of bladder cancer through their metabolite acrolein. Following high-dose cyclophosphamide treatment, the 12-year prevalence of bladder cancer is as high as 11%.
• Low daily fluid intake may be a contributing factor; the relative risk in persons who drink 6 cups of water per day is 0.49 compared with that in persons who drink one cup of water per day.
• Schistosomiasis caused by the parasite S haematobium can cause SCC; this is common in Egypt and the Nile River Valley.
• Long-term phenacetin use is a risk factor; this agent is no longer approved for use in the United States.
• Long-term placement of indwelling catheters is a risk factor; patients who have indwelling catheters for longer than 10 years should undergo bladder surveillance via cytology and cystoscopy.
• Artificial sweeteners (saccharin, cyclamate), when administered in high doses to laboratory animals, are risk factors for bladder cancer; no similar evidence has been shown in humans.
• The use of Aristolochia fangchi, a Chinese herb, has been implicated as a risk factor for both upper and lower tract TCC.
• Coffee and tea are not risk factors for bladder cancer.

Pathophysiology

As with most neoplasms, bladder carcinogenesis is a complex multistep process that is not fully understood. Activation of proto-oncogenes, loss or inactivation of tumor suppressor genes, and abnormal growth factor or receptor expression have been implicated.

Multiple mutations of chromosome 9 have been identified in superficial bladder cancer cells. Increased expression of the epidermal growth factor receptor and increased mutations of tumor suppressor genes (eg, TP53 and Rb) are common in patients with advanced bladder cancer. Mutations and nuclear accumulation of TP53 have been correlated with an increased grade, stage, and recurrence risk.

The risk of progression to muscle-invasive disease is associated with tumor grade, stage (Ta vs T1), size, number of lesions (solitary vs multiple lesions), previous tumor recurrence, and presence of CIS.

Presentation

Gross or microscopic hematuria is the initial presenting sign in 80%-90% of patients. Approximately 20% of patients have irritative symptoms such as urinary urgency, dysuria, or frequency. This presentation is typical in patients with diffuse CIS, which can be confused with a urinary tract infection and can result in a delayed diagnosis. With the more routine use of cross-sectional imaging, many bladder lesions are incidentally diagnosed. Patients with muscle-invasive disease can present with incidental or symptomatic obstructive hydroureteronephrosis or, less commonly, with metastatic deposits. These factors make bladder cancer a very uncommon incidental finding on autopsy.

Indications

Indications for radical cystectomy include the following:

• Infiltrating muscle-invasive bladder cancer without evidence of metastasis or with low-volume, resectable locoregional metastases (stage T2-T3b)
• Superficial bladder tumors characterized by any of the following:
• Refractory to cystoscopic resection and intravesical chemotherapy or immunotherapy (Up to 71% of these patients may progress to stage T2 within 5 years of initial recurrence.⁵ )
• Extensive disease not amenable to cystoscopic resection
• Invasive prostatic urethral involvement
• Stage-pT1, grade-3 tumors unresponsive to intravesical BCG vaccine therapy
• CIS refractory to intravesical immunotherapy or chemotherapy
• Palliation for pain, bleeding, or urinary frequency
• Primary adenocarcinoma, SCC, or sarcoma

Indications for urethrectomy include the following:

• Tumor in the anterior urethra
• Prostatic stromal invasion that is noncontiguous with the primary
• Positive urethral margin during radical cystectomy
• Diffuse CIS of bladder, prostatic ducts, or prostatic urethra (a relative indication)

Rarely, radical cystoprostatectomy is indicated for salvage treatment for recurrent prostate cancer or intractable hematuria following primary therapy with radiation.

Relevant Anatomy

The bladder is an extraperitoneal muscular urine reservoir that lies behind the pubis symphysis in the pelvis. At the dome of the bladder lies the median umbilical ligament, a fibrous cord that is anchored to the umbilicus and that represents the obliterated urachus. This ligament contains vessels that must be ligated when divided. The ureters, which transport urine from kidney to bladder, approach the bladder obliquely and posterosuperiorly, entering at the trigone. The intravesical ureteral orifices are roughly 2-3 cm apart and form the superolateral borders of the trigone. The trigone consists of the area between the interureteric ridge and the bladder neck. The bladder neck serves as an internal sphincter, which is sacrificed during a radical cystectomy.

In males, the seminal vesicles, vas deferens, ureters, and rectum border the inferoposterior aspect of the bladder. Anterior to the bladder is the space of Retzius, which is composed of fibroadipose tissue and the prevesical fascia. The dome and posterior surface of the bladder are covered by parietal peritoneum, which reflects superiorly to the seminal vesicles and is continuous with the anterior rectal peritoneum. In females, the posterior peritoneal reflection is continuous with the uterus and vagina.

The vascular supply to the bladder arrives primarily via the internal iliac (hypogastric) arteries, branching into the superior, middle, and inferior vesical arteries, which are often recognizable as lateral and posterior pedicles. The arterial supply also arrives via the obturator and inferior gluteal artery and, in females, via the uterine and vaginal arteries. Bladder venous drainage is a rich network that often parallels the named arterial vessels, most of which ultimately drain into the internal iliac vein.

Recent extensive anatomic pathology studies have determined that initial lymphatic drainage from the bladder is primarily into the external iliac, obturator, internal iliac (hypogastric), and common iliac nodes. Following the drainage to these sentinel pelvic regions, spread may continue to the presacral, paracaval, interaortocaval, and paraaortic lymph node chains. For a more detailed explanation of lymphatic drainage, see Treatment.

Contraindications

Contraindications to radical cystectomy include (1) bleeding diathesis, (2) evidence of gross, unresectable metastatic disease (unless performed for palliation), and (3) medical comorbidities that preclude operative intervention (eg, advanced heart disease, poor pulmonary mechanics, advanced age).

Current Value of Neoadjuvant Chemotherapy Prior to Cystectomy^[xxx]

Radical cystectomy with pelvic lymph node dissection remains the standard treatment for muscle–invasive bladder cancer. The quality of surgery is essential for optimal treatment results. The data from prospective randomized trials and meta–analyses provide support for preoperative application of platinum–based combination chemotherapy in all patients.

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer[xxxi]

Urology – Original Paper

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer

Objective  

To report the long-term follow up of patients with locally advanced bladder cancer treated with either adjuvant chemotherapy with gemcitabine/cisplatin (GC) or methotrexate, vinblastine, epirubicin, and cisplatin (MVEC) or no additional treatment after radical cystectomy, to examine various survival endpoints and factors associated with long-term survival.

Patients and methods  

Seventy-eight patients undergoing radical cystectomy for pathologic stage T3, T4 or lymph node–positive (N+) bladder cancer were divided to observation group (46 patients) and adjuvant chemotherapy group (32 patients). Data were obtained for recurrence free (RFS) and overall survival (OS).

Results  

One-, 2- and 5-year RFS rates were 74, 56.8 and 51.1% for chemotherapy arm, whereas these ratios were 50.6, 31 and 27.6% for control arm, respectively (P = 0.032). RFS rates were significantly better in patients with lymph node–negative disease than in those with positive lymph nodes for control arm (P = 0.007), but for the chemotherapy arm there was no statistical difference between patients with lymph node–negative and –positive disease (P = 0.28). Mean OS and RFS times were 31.03 and 28.4 months for chemotherapy arm, while they were 22.17 and 18.09 months for control arm, respectively (P = 0.142, P = 0.196). On multivariate analysis, lymph node metastasis and adjuvant chemotherapy remained significant independent prognostic factors for cancer-specific survival.

Conclusions  

Bladder cancer is chemosensitive, and using adjuvant chemotherapy is likely to improve the outcome of local treatment and to decrease the rates of distant metastases.

Use of radical cystectomy for patients with invasive bladder cancer

[xxxii]

Wednesday, 21 April 2010

Evidence-based guidelines recommend radical cystectomy for patients with muscle-invasive bladder cancer. However, many patients receive alternate therapies, such as chemotherapy or radiation. We examined factors that are associated with the use of radical cystectomy for invasive bladder cancer and compared the survival outcomes of patients with invasive bladder cancer by the treatment they received.

From linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 3262 Medicare beneficiaries aged 66 years or older at diagnosis with stage II muscle-invasive bladder cancer from January 1, 1992, through December 31, 2002. We examined the use of radical cystectomy with multilevel multivariable models and survival after diagnosis with the use of instrumental variable analyses. All statistical tests were two-sided.

A total of 21% of the study subjects underwent radical cystectomy. Older age at diagnosis and higher comorbidity were associated with decreased odds of receiving cystectomy (for those >/=80 vs 66-69 years old, odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.07 to 0.14; for Charlson comorbidity index of 3 vs 0-1, OR = 0.25, 95% CI = 0.14 to 0.45). Long travel distance to an available surgeon was associated with decreased odds of receiving cystectomy (for >50 vs 0-4 miles travel distance to an available surgeon, OR = 0.60, 95% CI = 0.37 to 0.98). Overall survival was better for those who underwent cystectomy compared with those who underwent alternative treatments (for chemotherapy and/or radiation vs cystectomy, hazard ratio of death = 1.5, 95% CI = 1.3 to 1.8; for surveillance vs cystectomy, hazard ratio of death = 1.9, 95% CI = 1.6 to 2.3; 5-year adjusted survival: 42.2% [95% CI = 39.1% to 45.4%] for cystectomy; 20.7% [95% CI = 18.7% to 22.8%] for chemotherapy and/or radiation; 14.5% [95% CI = 13.0% to 16.2%] for surveillance).

Guideline-recommended care with radical cystectomy is underused for patients with muscle-invasive bladder cancer. Many bladder cancer patients whose survival outcomes might benefit with surgery are receiving alternative less salubrious treatments.

Written by: Gore JL, Litwin MS, Lai J, Yano EM, Madison R, Setodji C, Adams JL, Saigal CS; the Urologic Diseases in America Project.

Reference: J Natl Cancer Inst. 2010 Apr 16. doi: 10.1093/jnci/djq121

PubMed Abstract PMID: 20400716

Treatment and outcome in muscle invasive bladder cancer[xxxiii]

A population-based survey
Tuesday, 20 April 2010

Department of Urology, University Medical Center Groningen, Hanzeplein 1, P.O. box 30.001, 9700 RB, Groningen, The Netherlands.

To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region.

Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were collected from the CCCN cancer registry. All had a follow-up of at least 5 years. Logistic regression analysis on treatments as well as survival analysis was performed.

The treatments were radical cystectomy in 205/548 (37.5%) patients. TUR plus radiotherapy in 246 (44.9%) and palliation in 97 (17.7%). Multivariate analysis identified TNM stage (P < 0.0001) and age (P < 0.0001) as independent variables for cystectomy. Hospital type and year of diagnosis were not significant different between patients treated by cystectomy versus other type of treatment. TNM stage (P < 0.0001), age (P = 0.0043), and comorbidity (P = 0.0028) were independent variables for disease-specific survival (DSS) after cystectomy.

In the CCCN region, only 1/3 of patients with MIBC were treated with radical cystectomy. TNM stage and age were identified as main variables for the choice for cystectomy. TNM stage, age, and comorbidity were independent variables for disease-specific survival after cystectomy.

Written by: Leliveld AM, Doornweerd BH, Bastiaannet E, Schaapveld M, de Jong IJ.

Reference: World J Urol. 2010 Apr 10. doi:10.1007/s00345-010-0546-2

PubMed Abstract PMID: 20383640

The management of BCG failure in non-muscle-invasive bladder cancer[xxxiv]

“A major dilemma among patients with non-muscle-invasive bladder cancer (NMIBC) and their physicians is the choice of an appropriate course of action following failure of intravesical bacillus Calmette-Guerin (BCG). Although classified the same, NMIBC actually consists of 2 biologically different diseases,

1. low-grade NMBIC who are likely to recur but rarely progress and,

2. high-risk T1 bladder cancer and/or carcinoma in situ (CIS or TIS) which often progresses to an aggressive muscle-invasive life threatening disease.

“While guidelines provide a good definition of BCG failure, unfortunately BCG failure cannot be accurately predicted on an individual basis. Nevertheless, with clinical and histologic parameters, risk groups should be identified because the window of curability in patients with BCG failure is narrow in the case of tumour progression to muscle-invasive cancer. Such window should be immediately targeted if possible for optimal outcome, either with conservative treatments with immunotherapy or with cystectomy. Immunotherapy agents include agents such as Urocidin, interferon-α and Vicinium. Risk factors include presence of CIS, early recurrence, recurrent vs. progressive tumor, T1 substage and gender. For patients with CIS or high-risk tumors failing BCG, the guidelines recommend cystectomy as the treatment of choice. However, cystectomies are often associated with impaired quality of life compared with conservative therapy. Thus, it remains necessary for the clinical research community to identify new methods where patients are able to keep their bladders while simultaneously keeping their tumors under control.

Prevention and management of complications following radical cystectomy for bladder cancer[xxxv]

Wednesday, 24 March 2010

Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.

This review focuses on the prevention and management of complications following radical cystectomy (RC) for bladder cancer (BCa).

We review the current literature and perform an analysis of the frequency, treatment, and prevention of complications related to RC for BCa.

A Medline search was conducted to identify original articles, reviews, and editorials addressing the relationship between RC and short- and long-term complications. Series examined were published within the past decade. Large series reported on multiple occasions (Lee [1], Meyer [2], and Chang and Cookson [3]) with the same cohorts are recorded only once. Quality of life (QoL) and sexual function were excluded.

The literature regarding prophylaxis, prevention, and treatment of complications of RC in general is retrospective, not standardised. In general, it is of poor quality when it comes to evidence and is thus difficult to synthesise.

Progress has been made in reducing mortality and preventing complications of RC. Postoperative morbidity remains high, partly because of the complexity of the procedures. The issues of surgical volume and standardised prospective reporting of RC morbidity to create evidence-based guidelines are essential for further reducing morbidity and improving patients’ QoL.

Written by: Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Månsson W, Sagalowsky A, Wirth MP.

Reference: Eur Urol. 2010 Feb 26. doi:10.1016/j.eururo.2010.02.024

PubMed Abstract PMID:20227172

Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy[xxxvi]

Monday, 22 March 2010

Servicio de Urología, Fundación Puigvert, Barcelona, España.

To assess the characteristics and outcomes of patients with non-muscle invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC) due to BCG failure.

Ninety-five (11%) of the 864 patients undergoing radical cystectomy (RC) at our center from 1989 to 2002 had received prior treatment with BCG. Of these, 62 (65.2%) underwent RC due to relapsing, high-risk NMIBC or CIS despite BCG therapy. A stage >/= pT2 tumor was reported in the cystectomy specimen in 17 (27%) of these patients, who were considered to have been understaged. RC was performed for clinical progression in 33 patients (34.7%). Their last transurethral resection before RC showed invasive disease. A retrospective analysis was made of the outcomes of patients who underwent RC for BCG failure and the clinical and pathological differences between understaged patients and those with clinical progression.

Five-year CSS was 90% in 45 patients with clinical and pathological NMIBC and 50.6% in 50 patients with progression to muscle-infiltrating disease (clinical progression and understaged) (p < 0,05). There were no differences in survival in patients with clinical progression as compared to understaged patients. Median time from tumor diagnosis to tumor progression was 24 months (10th-90th percentile, 6-98 months). Patients with clinical progression had significantly more T1 tumors (p = 0.015) in TUR before progression and more pT3 tumors (p < 0.01) in the RC specimen. Understaged patients more often had pathological pT4 stages (p < 0.02).

In patients with high-risk NMIBCs who fail BCG therapy, RC should be performed before progression because survival is decreased when the RC specimen shows muscle-invasive disease. High-grade T1 tumors are responsible for most early clinical progressions. Patients with NMIBC may have subclinical progression, mainly within the prostate.

Written by: Huguet J, Gaya JM, Sabaté S, Palou J, Villavicencio H.

Reference: Actas Urol Esp. 2010 Jan;34(1):63-70.

PubMed Abstract PMID:20223134

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer[xxxvii]

“BACKGROUND:

Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer-specific survival.

“METHODS:

Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared.

“increase in median lymph node yield, decreased mortality risk by 30%

Update of the Clinical Guidelines of the European Association of Urology on muscle-invasive and metastatic bladder carcinoma[xxxviii]

INTRODUCTION: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC.

OBJECTIVE: To review the new EAU guidelines for MiM-BC.

Evidence acquisition: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Evidence synthesis: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available.

Adjuvant chemotherapy is currently only advised within clinical trials.

Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy.

An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection.

Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons.

An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy.

Presently, there is no standard second-line chemotherapy.

CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

PMID: 20223133 [PubMed – as supplied by publisher]

Beyond the Abstract – Risk factor analysis in a contemporary cystectomy[xxxix]

BERKELEY, CA (UroToday.com) – Despite significant improvements in surgical technique, preoperative preparation and perioperative care since the inception of radical cystectomy (RC), the complication rate associated with this operation remains high [My emphasis]. Patients requiring RC are elderly with considerable associated comorbidities due to the strong association of cigarette smoking and urothelial bladder carcinoma. Diverse adverse event (AE) rates after RC for urothelial bladder carcinoma range from 25% to 64% and this variability is partly due to classification errors and under reporting and/or nonstandardized reporting of AEs in published series. Standardized reporting methods are essential to characterize RC outcomes to reliably compare complication rates and severity among institutions and surgical techniques.

In this study, we defined the frequency and severity of complications after RC in patients with urothelial bladder carcinoma using standard reporting methods and AE criteria. We also explored associations between important risk factors and various specific complications to better individualize perioperative risk assessment.

We observed at least 1 adverse event in 54.0% of patients and a grade 3–4 adverse event in 40.3%.[My emphasis] The most common grade 4 AEs were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. An association between body mass index, and any major adverse events was found after adjusting for confounding variables. Because of the large number of multiple comparisons made, we corrected our accepted p-value to avoid false-positive conclusions. Although not significant by this corrected p-value, we also observed an association between increasing age with ileus requiring total parenteral nutrition and new onset arrhythmia. These findings may warrant consideration of specific postoperative treatment and monitoring in older patients. Such measures may include pretreatment procedural patient selection, multimodal anti-ileus therapy, and prolonged postoperative telemetry in older patients.

An analysis of upper urinary tract recurrence following radical cystectomy for bladder cancer[xl]

Transitional cell carcinoma of the urothelium is often multifocal, and subsequent tumors may occur anywhere in the urinary tract afer treating the initial carcinoma. The risk of an upper urinary tract recurrence following a radical cystectomy has been reported to be approximately 2 to 8%, but there are few reports with regard to the pattern and predictive factors of upper tract recurrence. We report here the incidence and pattern of upper tract recurrence following a radical cystectomy. Of the 166 patients 5 (3%) had upper tract recurrence. The prognosis of upper urinary tract recurrence is significantly better than other site of recurrence.

Article in Japanese.

Written by: Sugi M, Fukui K, Yoshida K, Inui H, Kawakita S, Murota T, Kinoshita H, Matsuda T.

Reference: Hinyokika Kiyo. 2010 Feb;56(2):87-90.

PubMed Abstract PMID:20185992

Predictive factors and long term carcinogenic results of patients who no longer have residual tumors (stage pT0) on specimens of total cystectomy carried out for cancer of the bladder[xli]

Monday, 15 February 2010

Service d’urologie, clinique urologique, CHU Hôtel-Dieu, 1, place Alexis-Ricordeau, 44000 Nantes, France.

The aim of our study was to evaluate predictive factors and long-term carcinogenic results for patients who had had a total cystectomy for cancer of the bladder and whose final histological results did not show evidence of a residual tumor.

From 1988 to 2002, 192 patients had a total cystectomy for a bladder tumor. No residual tumor (pT0) was evident in the specimens of cystectomy of 22 patients (11.5%). None of the patients had distant metastasis or ganglions at the time of the initial examination.

Predictive factors for having no residual tumors based on the specimen of cystectomy (pT0) were an antecedent of neo-adjuvant chemotherapy (p=0.0079), an interval between the resection of the bladder and the cystectomy of more than 12 weeks (p=0.0014) and a resection of the initial bladder considered complete (p=0.0036). The average treatment of these 22 patients was 70+/-46 months. During treatment, two patients (9%) had a recurrence in the pelvis and 10 patients died including one from the development of his cancer of the bladder. Global, specific and non-recurrence survival at five years were 75%, 100% and 94%, respectively. We revealed better specific survival (p=0.0007) and without relapse (p< 0.0001) in patients who no longer had a tumor on the specimen of cystectomy (pT0) compared with patients who had a residual tumor (pT+) but with no difference in global survival (p=0.0574).

The absence of residual tumors (pT0) on a specimen of total cystectomy for cancer of the bladder was a good factor for prognosis regarding long-term survival even if tumor development was observed. Complete resection and neo-adjuvant chemotherapy probably played a beneficial role in the future of these patients.

Written by: Hitier M, Marconnet L, Luyckx F, Branchereau J, Braud G, Karam G, Bouchot O, Rigaud J.

Reference: Prog Urol. 2010 Feb;20(2):130-137. doi:10.1016/j.purol.2009.07.004

PubMed Abstract PMID:20142054

Outcome of treatment of bladder cancer: A comparison between low-volume hospitals and an oncology centre[xlii]

Thursday, 11 February 2010

Department of Urology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

To evaluate the effect of volume of cystectomies in the Greater Amsterdam region on postoperative outcomes.

All primary bladder tumours diagnosed between 1989 and 2003 were selected from the Amsterdam Cancer Registry, a population-based cancer registry (population 3.0 million). For all patients who underwent cystectomy during 1989-2003 at 20 participating hospitals, medical records were reviewed for information on postoperative mortality, locoregional recurrences and relative risk of death. To assess the effect of volume, outcomes at an oncology centre and low-volume hospitals were compared.

During 1989-2003 a total of 1,185 cystectomies were performed in 20 hospitals of the Greater Amsterdam region. Postoperative mortality was 3.2%. During 1989-1997, 8% of cystectomies were performed at the oncology centre, increasing to 30% in 1998-2003. Although postoperative mortality at this centre decreased from 4.0% in 1989-1997 to 1.1% in 1998-2003, the latter percentage was not statistically significantly different from the other hospitals during 1998-2003 (OR 0.3; P = 0.09). No statistically significant difference in locoregional recurrence rate and in the relative risk of death was observed between the oncology centre and all other hospitals combined.

We observed a lower postoperative mortality rate in the oncology centre compared to the low-volume hospitals; however, this difference did not reach statistical significance. We could neither prove a statistically significant relation between hospital volume, local recurrence rate and survival after cystectomy. To answer the question if centralisation of cystectomies is beneficial more procedures have to be compared.

Written by: de Vries RR, Visser O, Nieuwenhuijzen JA, Horenblas S.

Reference: World J Urol. 2010 Feb 4.

PubMed Abstract PMID:20130885

Survival after cystectomy for invasive bladder cancer[xliii]

Wednesday, 03 February 2010

Department of Urology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

To determine the difference in survival after cystectomy between patients presenting with primary muscle infiltrating bladder cancer and patients with progression to muscle infiltration after treatment for initial non-muscle-invasive bladder cancer (NMIBC).

We retrospectively analyzed the files of 188 patients who underwent cystectomy for transitional cell carcinoma between 1987 and 2005. Two groups were defined: patients presenting with muscle-invasive tumours and those progressing to muscle invasion after initial treatment. This second group was further divided into low-intermediate and high risk according to the EAU grouping for NMIBC.

The 5-year disease specific survival (95% confidence intervals) for all patients was 50%(42-59%); 49%(40-60%) in the primary muscle infiltrating group and 52%(37-74%) in the progressive group (p = ns). The 5-year disease specific survival in the progressive group according to EAU risk groups was 75%(58-97%) for the initially diagnosed low-intermediate risk tumours and 35%(17-71%) for the initially diagnosed high-risk tumours (p = 0.015). The percentage of patients with non-locally confined tumours (pT3/4-N0//any pT-N+) was 31%//45% and 24%//46% in the primary muscle infiltrating and progressive group, respectively.

Despite close observation of patients treated for non-muscle-invasive bladder cancer, the survival of patients who progress to muscle invasion is not better than survival of patients presenting with primary muscle infiltrating cancer. Patients with high-risk non-invasive tumours (EAU risk-categories) who progress to muscle-invasive disease have a worse prognosis compared to patients with low or intermediate risk tumours.

Written by: de Vries RR, Nieuwenhuijzen JA, Vincent A, van Tinteren H, Horenblas S.

Reference: Eur J Surg Oncol. 2010 Jan 22. doi:10.1016/j.ejso.2009.11.012

PubMed Abstract PMID:20097512

External stoma and peristomal complications following radical cystectomy and ileal conduit diversion[xliv]

“An ileal conduit is the most common urinary diversion following radical cystectomy for invasive bladder cancer. Unlike internal complications commonly described in urological literature, reports about the incidence of external complications are sparse.

A Medline database review (1996-2008) of English-language literature was conducted to: 1) describe and compare external stoma and peristomal complications and complication rates among outpatients with ileal conduit diversion following radical cystectomy, and 2) summarize commonly used prevention and management strategies. Fourteen publications (mostly retrospective, single-center studies) met inclusion criteria.

The reported incidence of complications ranged from 15% to 65%.

Divided according to pathogenesis, the most commonly reported complications are 1) stoma or abdominal wall-related changes – parastomal hernia, stoma prolapse, stenosis, and retraction; and 2) peristomal skin changes – chemical injury: irritant contact dermatitis, pseudoverrucous lesions, and alkaline crustations; mechanical injury: pressure ulcers, skin stripping injuries, mucocutaneous separation; infection: candidiasis, folliculitis; immunologic disorders: allergic contact dermatitis; and disease-related lesions: varices, pyoderma gangrenosum, malignancy. Peristomal complications also appear to be under-recognized and under-reported.

Research to establish the validity and reliability of assessment tools and long-term follow-up studies are needed to improve the evidence-base of prevention and care.

A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy[xlv]

“To evaluate the clinicopathological efficacy of neoadjuvant erlotinib (an epidermal growth factor receptor, EGFR, inhibitor) for invasive bladder cancer in patients undergoing radical cystectomy (RC) as despite definitive surgical therapy, only half of patients undergoing RC will have long-term disease-free survival, and effective adjunctive therapies, especially using agents with lower toxicity, would be a significant advance in the treatment of invasive bladder cancer.

“The EGFR inhibitor erlotinib, when administered in the neoadjuvant setting, can have beneficial effects in terms of surgical pathology and short-term clinical outcomes in patients undergoing RC for invasive bladder cancer.

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria[xlvi]

Thursday, 28 January 2010

Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations.

We retrospectively reviewed consecutive radical cystectomies done for urothelial bladder carcinoma at our institution between January 2004 and September 2006. Adverse events within 90 days postoperatively were recorded. We explored the association of important risk factors with the overall complication rate and specific complications.

A total of 283 patients were included in the study. Complete 90-day followup data were available on 90% of patients. Median age was 70 years (IQR 62-75). Median body mass index was 26.8 kg/m(2) (IQR 24.4-31.0). At least 1 adverse event was observed in 152 patients (54.0%) and a grade 3-4 adverse event was observed in 40.3%. The most common grade 4 adverse events were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. No patient died during followup. An association between body mass index, and any and major adverse events was found after adjusting for confounding variables.

More than 50% of patients experience an adverse event after radical cystectomy and 40% are major. Body mass index is independently associated with adverse events in these patients. These findings are important for individualized risk assessment, patient counseling and uniform assessment of quality care.

Written by: Svatek RS, Fisher MB, Matin SF, Kamat AM, Grossman HB, Nogueras-González GM, Urbauer DL, Kennedy KA, Dinney CP.

Reference: J Urol. 2010 Jan 16. doi:10.1016/j.juro.2009.11.038

PubMed Abstract PMID:20083264

Urinary diversion and morbidity after radical cystectomy for bladder cancer[xlvii]

Adjusting for case-mix differences between reconstructive groups, continent diversions conferred a lower risk of medical, surgical, and disposition-related complications that was statistically significant for bowel (3.1% lower risk; 95% confidence interval [95% CI], -6.8% to -0.1%), urinary (1.2% lower risk; 95% CI, -2.3%, to -0.4%), and other surgical complications (3.0% lower risk; 95% CI, -6.2% to -0.4%), and discharge other than home (8.2% lower risk; 95% CI, -12.1% to -4.6%) compared with ileal conduit subjects. Older age and certain comorbid conditions, including congestive heart failure and preoperative weight loss, were associated with significantly increased odds of postoperative medical and surgical complications in all subjects. CONCLUSIONS: Mode of urinary diversion after radical cystectomy for bladder cancer is not associated with increased risk of immediate postoperative complications. These results may encourage broader consideration of continent urinary diversion without concern for increased complication rates. Cancer 2010. © 2010 American Cancer Society.

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort[xlviii]

Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle–invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer[xlix]

Context

High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.”

Objective

To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment.

Evidence acquisition

A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained.

Evidence synthesis

The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment.

Conclusions

Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.

Take Home Message

High-grade T1 bladder cancer has a high propensity to recur and progress. Risk stratification based on pathologic features at initial transurethral resection or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.

Impact of comorbidity on survival of invasive bladder cancer patients, 1996-2007: A Danish population-based cohort study[l]

Friday, 27 November 2009

Department of Urology, Viborg Hospital 8800, Viborg, Denmark; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, Tennessee.

To examine (i) the prevalence of comorbidity among invasive bladder cancer (IBC) patients, and (ii) the effect of comorbidity on IBC survival and mortality in Northern Denmark. Comorbidity has shown to be associated with treatment selection and survival in patients who undergo radical cystectomy for IBC.

Patients with a diagnosis of IBC from Danish hospitals between 1996 and 2007 within a population of 1.6 million were identified through the Danish National Patient Registry. From hospital diagnosis data, we computed Charlson Comorbidity Index scores (0, 1-2, 3+) for IBC patients and computed absolute survival and relative mortality estimates according to comorbidity level.

We identified 3997 patients with IBC among whom 1715 (43%) had comorbidities. The prevalence of comorbidity tended to increase during the study period with those having scores 3+ increasing from 8%-12%. Three- and 5-year mortality rates were higher for patients with comorbidity, with mortality rates more than 2-fold higher among those with scores of 3+ and 1.5-fold higher among those with scores of 1-2 compared with no comorbidity. Generally, the same pattern was seen for 1-year relative survival rates.

Comorbidity was seen among 43% of IBC patients and severe comorbidity was a predictor of poorer survival.

Written by: Lund L, Jacobsen J, Clark P, Borre M, Nørgaard M.

Reference: Urology. 2009 Nov 13 doi:10.1016/j.urology.2009.07.1320

PubMed Abstract PMID:19914698

Robot-assisted radical cystectomy: intermediate survival results at a mean follow-up of 25 months

Tuesday, 17 November 2009

Pathology, Mayo Clinic, Phoenix, AZ.

To assess the overall and disease-specific survival rates of patients undergoing robot-assisted radical cystectomy (RARC) compared with historical open cystectomy.

Survival, pathological and demographic data were collected on all patients undergoing RARC for bladder cancer from both Tulane University Medical Center and Mayo Clinic Arizona. Of a total of 80 RARCs we only included those with a follow-up of >/=6 months from surgery. Survival curves were compared with those from historical series of open cystectomy.

Of the 80 patients 59 were identified as having a follow-up of >/=6 months from the date of surgery. The mean (range) follow-up was 25 (6-49) months. Overall survival rates at 12 and 36 months were 82% and 69%, respectively, and disease-specific survival rates were 82% and 72% at 12 and 36 months, respectively. These results are comparable to survival rates from open cystectomy. As expected, patients with lymph node-positive disease fared worse than those with lymph node-negative disease. Patients with extravesical lymph node-negative disease (pT3, pT4) fared worse than patients with organ-confined lymph node-negative disease. Also, patients with lymph node-positive disease fared worse than those with extravesical lymph node-negative disease, which is consistent with historical results of open cystectomy.

RARC has a comparable survival rate to open cystectomy in the intermediate follow-up. Further study with a longer follow-up and more patients is necessary to determine any long-term survival benefits.

Written by: Martin AD, Nunez RN, Pacelli A, Woods ME, Davis R, Thomas R, Andrews PE, Castle EP.

Reference: BJU Int. 2009 Nov 9 doi:10.1111/j.1464-410X.2009.09042.x

PubMed Abstract PMID:19903170

Invasive TCC in the Elderly: Radical cystectomy?[li]

Friday, 28 August 2009

PORT DOUGLAS, AUSTRALIA (UroToday.com) – To reduce morbidity in the elderly patient, conservative multimodal therapy concepts for invasive bladder cancer are emerging as an alternative to radical cystectomy. It was the aim of the study to report on our recent experience with peri- and postoperative morbidity of radical cystectomy in patients 75 years and older compared to younger patients.

METHODS
Medical records of 326 consecutive patients undergoing radical cystectomy in our institution from May 2004 through April 2008 were reviewed. Intra- and perioperative parameters have been analyzed to assess perioperative morbidity and mortality of radical cystectomy in these patients.

RESULTS
Eighty-five of 326 patients (26%) were ≥75 years (75 – 95) old. ASA-score was equal 3 or greater in 51% of patients ≥75 years and 32% of patients <75 years. Ileal conduit was performed in 83% of patients ≥75, 16% received an ileal neobladder compared to 46% and 51%, respectively, in patients <75. A total of 33 patients (39%) in the older patient group received blood transfusions intraoperatively compared to 76 patients (32 %) in the younger age group. In 6 patients ≥75 years (7.1%) and 17 patients < 75 (7.1%) open surgical revision was necessary, perioperative complication rate was 22% and 21%, respectively. The most common complications were wound dehiscence (5.9% vs. 7.5%), infections (4.7% vs. 4.6%), and pulmonary embolism (3.5% vs. 2.1%). Perioperative mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the younger age group.

CONCLUSIONS
Our data show that radical cystectomy can be offered to the elderly patient with acceptable morbidity. Because of higher comorbidity rate in elderly patients compared to younger patients, therapeutic decision for radical cystectomy in the elderly patient should be made carefully and individually. Nevertheless our results demonstrate that age itself is not a main criterion which has to be considered strongly in the decision-making for radical cystectomy.
Written by: Tilki D, Zaak D, Gerwens N, Seitz M, Stief C, and Reich O
Department of Urology, Ludwig-Maximilians-University, Munich, Germany
For presentation at the 25th Annual Meeting of the Urological Research Society (URS), August 10 – 14, 2009, Thala Beach, North Queensland, Australia

Management of muscle invasive disease[lii]

Written by David P. Wood, MD    Tuesday, 18 August 2009

RIO DE JANEIRO, BRAZIL (UroToday.com) – Transurethral resection alone can be effective in muscle invasive tumors. 20% of patients will have no cancer on re-resection and 15% will have Ta or T1 disease. Patients with no tumor on re-resection do very well, but those with any residual cancer have a significantly worse survival rate.

It is worthwhile to perform a repeat TURBT in patients with muscle invasive disease. If T0, consider observation, perhaps with BCG therapy. If any residual disease is found on the repeat TURBT then chemotherapy and radiation or cystectomy is recommended. Neo adjuvant chemotherapy has been shown to provide a 5% absolute survival benefit for patients undergoing a radical cystectomy. Some experts suggest that this difference is too small to recommend for patients with cT2 disease, but randomized trials show that even in this group, neoadjuvant chemotherapy is beneficial. Most experts recommend neoadjuvant chemotherapy for patients with hydronephrosis or with cT3-cT4 disease. Chemotherapy can be effective even in unresectable tumors with 30% of eligible patients having no tumor in the radical cystectomy specimen and a 50% two-year survival rate. It is critical to have complete resolution of nodal disease and the examination under anesthesia must reveal a respectable bladder after chemotherapy before proceeding with radical cystectomy. Gemcitabine and Cisplatin is the best regimen and should provide a 30% complete response rate. Using a standardized preoperative, operative, and postoperative pathway will improve the results after radical cystectomy. Key new changes include:

no bowel prep except nothing by mouth (NPO) after midnight
no nasogastric tube
limit intravenous fluids during surgery
24 hours of antibiotics only
start Heparin 5,000 units subcutaneous day of surgery
use ketoralac for postoperative pain relief with patient controlled morphine anesthesia
early ambulation on post-operative day (POD) #1
start clear liquids of POD # 2 and soft diet on POD #3

The main problem with radical cystectomy in the elderly is the urinary diversion. Most elderly patients should receive an ileal conduit (unless their creatinine is < 2mg/dl), if they have good bowel function, are able to perform chronic intermittent catheterization, and have good liver function. Most elderly patients lack the desire to perform intermittent catheterization and thus ileal conduit is the preferred diversion in the elderly. The following table shows an appropriate follow-up schedule after radical cystectomy.

Presented by David P. Wood, MD; Khaled Hafez, MD; Carlos Jose Andrade, MD; and Charles Rosser, MD at the VI Maratona Urológica do Rio de Janeiro – August 14 – 15, 2009.

Bladder cancer in the elderly[liii]

Tuesday, 18 August 2009

RIO DE JANEIRO, BRAZIL (UroToday.com) – A recent study from Vanderbilt University detailed the outcomes of 382 patients undergoing radical cystectomy of whom 44 were 75 years of age or older.

This group reported a 26% complication rate; 22% minor and 4% major complications. The mean hospital stay was 7 days. Unfortunately, only 29% were alive at 2 years with 91% disease-free survival rate. Elderly patients undergoing a palliative cystectomy have a much higher complication rate and poor two-year survival thus palliative cystectomy should be done only in extreme conditions. The performance status of the elderly patient is the most important determinant of long-term outcome after radical cystectomy. ECOG >1 portends a poor outcome. Use of the Pre-operative assessment of Co-morbidity evaluation (PACE) is very accurate at determining hospital outcomes. Chemo-radiation therapy should be considered for elderly patients, especially those with a poor performance status. Complete transurethral resection is appropriate if there is no tumor in a repeat transurethral resection. If there is residual cancer, then chemo-radiation or surgery is required. Radical cystectomy is difficult to tolerate in the elderly and many require short-term recovery in a rehabilitation institute.

Presented by Charles Rosser, MD at the VI Maratona Urológica do Rio de Janeiro – August 14 – 15, 2009.

Complications and Mortality After Radical Cystectomy for Bladder Transitional Cell Cancer[liv]

Giacomo Novara, Vincenzo De Marco, Maurizio Aragona, Rafael Boscolo-Berto, Stefano Cavalleri, Walter Artibani, Vincenzo Ficarra: Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Padua, Italy

Purpose

We evaluated early postoperative complications and 3-month mortality after radical cystectomy using a standardized method to report complications.

Materials and Methods

We retrospectively collected data on all 358 consecutive patients who underwent radical cystectomy for nonmetastatic bladder transitional cell carcinoma at a tertiary academic referral center from January 2002 to December 2006. The Martin criteria were used to report complications, which were graded according to a 5-grade modification of the Clavien system.

Results

A total of 231 complications occurred in 174 patients (49%), of which 13% were grades 3 to 5. The 3-month mortality rate was 3%. After evaluating the whole patient cohort American Society of Anesthesiologists score was the only covariate significantly associated with grade 3 to 5 complications on univariate analysis. Subgroup analysis limited to patients with an orthotopic ileal neobladder showed that female gender (HR 0.204, p = 0.017) and American Society of Anesthesiologists score (HR 2.851, p = 0.013) were independent predictors of grade 3 to 5 complications on multivariate analysis.

Conclusions

When applying a standardized methodology to report early morbidity, about 50% of patients undergoing radical cystectomy had complications within 3 months of surgery. Although most complications were minor, about 13% of patients experienced grade 3 to 5 events, resulting in a 3-month mortality rate of 3%. American Society of Anesthesiologists score was significantly associated with major complications, while on subgroup analysis in patients who received an orthotopic ileal neobladder female gender was also an independent predictor of major complications.

Complications Following Radical Cystectomy for Bladder Cancer in the Elderly[lv]

Context

The incidence of bladder cancer increases with advancing age. Considering the increasing life expectancy and the increasing proportion of elderly people in the general population, radical cystectomy will be considered for a growing number of elderly patients who suffer from muscle-invasive or recurrent bladder cancer.

Evidence synthesis

Perioperative morbidity and mortality are increased and continence rates after orthotopic urinary diversion are impaired in elderly patients undergoing radical cystectomy. Complications are frequent in this population, particularly when an extended postoperative period (90 d instead of 30 d) is considered.

Take Home Message

Elderly patients receiving radical cystectomy and urinary diversion are at a high risk of perioperative complications. Careful perioperative management and surveillance in experienced and properly staffed centers may improve outcome in this population.

=============================================================

The following article seems to be saying:

Positive surgical margins means that there are positive signs of cancer still remaining at the margins of the surgically removed area; negative that there are none – the patient is effectively clear of the cancer. (Note that http://urology.jhu.edu/newsletter/prostate_cancer410.php for prostate cancer argues that +ve margins does not necessary mean that cancer is still there).

So this article is saying that 88.4% had no observable cancer after surgery, 11.6% did have.  The former had poorer outcomes – 9% survived overall and 18% had disease specific survival (presumably meaning that 9% died of something else?). From an analysis of the data, the authors conclude (without seemingly giving any data on this) that these patients (those with some cancer left in them) would be better off having “meticulous pelvic lymph node dissection”.

However, 48% those who appeared clear (negative surgical margins) survived 5 years; and of the 52% who didn’t, 17% (difference between the 48% and the 68% who didn’t die of cancer) died of something else – so 35% died of their cancer returning.

From this I deduce a couple of things.

First, as we know, RC gives a relatively high chance of survival, some research quoting the surgery made a critical difference to the overall survival – 44% over half of those who had RC died, whether they were initially declared clear or not.

Second. Those who did have negative margins (that is, detectable cancer adjacent to the surgical action) had a significant extra chance of dying – about 5 times on these figures.

A Thorough Pelvic Lymph Node Dissection in Presence of Positive Margins Associated With Better Clinical Outcomes in Radical Cystectomy Patients[lvi]

Daniel Cantera Corresponding Author (Department of Surgery, Division of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania), Thomas J. Guzzoa, Matthew J. Resnicka, Meredith R. Bergeyb, Seema S. Sonnadb, John Tomaszewskic, Keith VanArsdalena, S. Bruce Malkowicza

Objectives

To evaluate the effect of positive surgical margins in patients with muscle-invasive transitional cell carcinoma of the bladder on survival.

Methods

A retrospective evaluation of a prospectively maintained radical cystectomy database consisting of the data from 344 patients was performed. Cox regression analysis was done, and Kaplan-Meier tables were developed to evaluate the contribution of this finding to clinical outcomes.

Results

A total of 304 (88.4%) patients had negative surgical margins in the radical cystectomy specimen, and 40 (11.6%) had positive surgical margins. On univariate analysis, positive surgical margins conferred a significant risk of poorer clinical outcomes. The 5-year overall (OS) and disease-specific survival (DSS) rate was 9% and 18% for patients with positive margins compared with 48% and 65% for patients with negative margins, respectively. The multivariate analysis demonstrated a significant independent risk of decreased recurrence-free survival, DSS, and OS for patients with positive surgical margins. The corresponding hazard ratios were 2.29 (95% confidence interval 1.54-3.41, P < .001), 1.71 (95% confidence interval 1.15-2.56, P < .009), and 1.70 (95% confidence interval 1.23-2.34, P < .001). Despite these findings, patients with positive margins and node-negative disease experienced improved DSS and recurrence-free survival (P = .001 P and = .009, respectively) if >15 lymph nodes were removed during surgery.

Conclusions

The presence of positive surgical margins in the pathologic specimen confers a significant independent risk of reduced recurrence-free survival, DSS, and overall survival. Nevertheless, patients with positive surgical margins will still benefit from a meticulous pelvic lymph node dissection.A Comparison of Postoperative Complications in Open versus Robotic Cystectomy[lvii]

Monday, 20 July 2009

Weill Cornell Medical College, Department of Urology, New York, NY, USA.

 

Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer (BCa). However, reduction in postoperative morbidity relative to the open approach has not been demonstrated. OBJECTIVE: To compare complication rates in patients undergoing robotic versus open radical cystectomy (RC).

A prospective cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC, 83 robotic RC.

Intervention: Open or robotic RC with urinary diversion.

Demographic, perioperative, and complication data were recorded prospectively. Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale. Data were evaluated using chi(2) and multivariate logistic regression analyses.

At 30 d, the open group demonstrated a higher overall complication rate (59% vs 41%; p=0.04) as well as more major complications (30% vs 10%; p=0.007). At 90 d, the overall complication rate was greater in the open group, but this was not statistically significant (62% vs 48%; p=0.07). However, there was a significantly higher major complication rate in the open cohort (31% vs 17%; p=0.03). When subjected to logistic regression analysis, robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists (ASA) score (3-4) and longer surgical time were independent predictors of major complications. Though this is one of the largest published RC series, the sample size is relatively small. Moreover, despite the two patient cohorts being similarly matched, the study was not performed in a randomized fashion.

Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy. Robotic cystectomy is an independent predictor of fewer overall and major complications. Until long-term oncologic results are available, robotic cystectomy should still be considered investigational.

Written by: Ng CK, Kauffman EC, Lee MM, Otto BJ, Portnoff A, Ehrlich JR, Schwartz MJ, Wang GJ, Scherr DS.

Reference: Eur Urol. 2009 Jun 10. doi:10.1016/j.eururo.2009.06.001

PubMed Abstract PMID:19560255

Neobladder vs. Ileal Conduit[lviii]

Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion After Cystectomy – A Quality-Of-Life Based Comparison

Friday, 17 July 2009

Radical cystectomy remains the gold standard in treatment of muscle invasive bladder cancer.

Evolution of pathological guidelines has empowered centres to offer orthotopic substitution (OBS) to patients undergoing radical cystectomy. We compared health-related quality of life (HRQoL) between patients who underwent OBS or ileal conduit urinary diversion(ICD) following radical cystectomy.

A total of 57 patients who underwent cystectomy were assessed pre-operatively using Karnofsky performancescale (KPS). Of these, 52 patients (28 OBS and 24 ICD) who responded to a postal questionnaire consisting of SF-36 and a functional index questionnaire were included.

Median age of patients was 70 years. Pre-operative KPS scores were similar. All eight HRQoL scales were favourable in both groups. OBS patients had significantly better physical functioning. In the cohort, 42% of men with OBS and 25% of diversions could maintain an erection to varying degrees. Of the OBS patients, 85% were continent with two patients reporting reduced QoL with pad usage. Of ICD patients, 63% felt less complete and 42% were embarrassed due to the stoma, with58% apprehensive of stomal leakage. Of OBS patients, 96% had significant relationships and a more active life-style.

In a similar age-group population, there was no significant difference in most QoL indices but body image issues persist in ICD patients. OBS patients had significantly better physical function, continuing to have a more active lifestyle. They attained urethral voiding with good continence. A detailed discussion of long-term functional outcome would engender a realistic expectation allowing better adaptation.

Written by: Philip J, Manikandan R, Venugopal S, Desouza J, Javlé PM.

Reference: Ann R Coll Surg Engl. 2009 Jun 25. doi:10.1308/003588409X432293

PubMed Abstract  PMID:19558757

This research gives some hope to those with non-muscle invasive BC who defer/refuse/cannot have RC.

Between 1996 and 2002, 1,133 patients were treated with single stage radical cystectomy as monotherapy for invasive bladder cancer. A randomly selected 776 cases (70%) were used as a reference series. The remaining 357 cases (test series) were used for external validation. Survival estimates were analyzed using univariate and then multivariate appraisal. The results of multivariate analysis were used for risk group stratification and construction of a nomogram, whereas all studied variables were entered directly into the artificial neural networks.

Overall 5-year disease-free survival was 64.5% with no statistical difference between the reference and test series.

===========================================================

Analysis of Perioperative and Survival Outcome of RC[lix]

Friday, 03 July 2009

Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA.

To review the outcomes in a large group of patients treated with radical cystectomy (RC) for urothelial cancer (UC) of the bladder, by one surgical team.

In all, 504 patients had RC for UC of the bladder between 1992 and 2007; 432 met the inclusion criteria and were analysed for survival and disease recurrence.

Of the 432 patients, (mean age 69 years; mean follow-up 38 months, range 1-172), 240 (56%) and 179 (41%) had an ileal conduit and orthotopic neobladder for urinary diversion, respectively. The mortality rate within 30 days of RC was 2%; 105 (24%) patients developed local and/or distant recurrence with a mean interval of 13.6 months. The overall survival, recurrence-free survival (RFS) and disease-specific survival (DSS) at 5 years was 58%, 64% and 74%, respectively, and 43%, 62% and 68% at 10 years. The 5-year RFS and DSS for those with organ-confined, node-negative tumours was 81% and 91%, compared to 46% and 56% in those with extravesical extension and lymph node-negative tumours. The RFS and DSS of patients with lymph node metastasis at 5 years was 29% and 40%, respectively.

Our study reaffirms that RC with bilateral pelvic lymph node dissection offers a reasonable possibility of disease control at 5 years, with a DSS of 74%. However, there is a need for an earlier diagnosis and effective systemic therapy if additional gains in survival are to be delivered.

Written by: Manoharan M, Ayyathurai R, Soloway MS

Reference: BJU Int. 2009 Jun 10. Epub ahead of print.
doi:10.1111/j.1464-410X.2009.08625.x

PubMed Abstract PMID:19519764

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy[lx]

Thursday, 02 July 2009

Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, Texas.

 

In a retrospective study of Southwestern Oncology Group (SWOG)-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and >/=10 pelvic lymph nodes (LNs) removed.

The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins.

Of 154 patients who received NC, 68 (44.2%) were < P2 (P0, Pa, P1, or carcinoma in situ [CIS]) at RC, 46 (29.9%) were P0, and the remainder had P2+ disease or did not undergo RC. In 115 patients who had RC with negative surgical margins, compared with P0 patients, those with residual Pa, P1, or CIS appeared to have worse OS (P = .054); OS was significantly worse for patients with residual P2+ disease (P = .0006). LN-positive (LN+) disease was found to be associated with worse OS than LN-negative (LN-) disease (P = .0005). Patients with LN- disease (ie, those with < 10 LNs removed) appeared to have inferior OS compared with those with 10+ LNs removed (P = .079). The combination of pre-NC clinical stage and post-RC pathologic stage was found to be predictive of OS (P < .0001).

NC and RC with negative surgical margins for bladder cancer followed by pathologic P0 and LN- disease were found to correlate with improved OS. A combination of baseline clinical stage and post-RC pathologic stage may better predict OS.

Written by: Sonpavde G, Goldman BH, Speights VO, Lerner SP, Wood DP, Vogelzang NJ, Trump DL, Natale RB, Grossman HB, Crawford ED.

Reference: Cancer. 2009 Jun 10. Epub ahead of print. doi:10.1002/cncr.24466

PubMed Abstract PMID:19517476

===========================================================

26/06/2009 23:32

Hi Linda,

Many thanks for that advice and the refs – very useful addition to my ‘library’ if and when I decide to attempt to go down the RC route.

However, the research since then does paint a more positive picture for retaining the bladder until there’s a noticeable resurgence.

So with that, plus improved procedures, increased evidence of effective CAM (I’m particularly struck by www.howtostopcancer.com J Dean 2009 Nile River Publications Inc, which has confirmatory orthodox research to support it), gives me hope that I can keep going with my bladder (which I’ve got attached to ….. haha).

But I also take note, as you emphasise, that the UK docs are opposed to RC for metastasised BC on the basis, presumably, that once the seeding has started then it is too late (which is probably based on the idea that any seeds have found fertile ‘soil’ – itself now a dubious concept). I think this is wrong; I’ve come round to thinking the USA idea that the cancerous bladder continues to be a source of seeding and would need to be removed. I also agree that there would need to be a 10+ removal of infected/suspect nodes for it to have the most chance of being effective.

Kind regards, Ian

———————————————————————

From: Linda Weyand (lweyand@AOL.COM) Sent: 26 June 2009 20:22:32

Hi, Ian,
Several years ago when research reports showing neoadjuvant chemotherapy being advantageous were first published, Dr. Herr gave a presentation about good surgery after neoadjuvant chemotherapy having as much or more to due with long-term survival than the neoadjuvant chemo itself. If I am rememberting right, his position was that whether the patient had good surgery after the chemotherapy might be making the difference in the survival rates. He stated that all patients that had a complete response to the chemotherapy and refused cystectomy had relapsed and died. Remembering this statement and others that he made during this presentation is why I was so pushy about your needing a cystectomy when you first wrote the List. Also, since I know how “normal” life can be without a bladder, I just felt and still feel that adding cystectomy surgery to your fight against bladder cancer would be for the best. When you first joined the List, I looked on the Internet for this presentation of Herr’s without luck, but it just occurred to me to check the List archives for the link that I posted at the time. Fortunately, I found it and it still works! You can view it as a slide show with audio or as a transcript with small pictures of the slides. Here it is:
‘Surgical Variables Impact Bladder Cancer Outcomes”
http://www.webtie.org/sots/Meetings/Genitourinary/SUO_12_13_14_2002/lectures.htm

One of the aspects of good surgery that Herr discusses in the above presentation is the extent of lymph node removal. On slide 11, he said, “And the patients who had more nodes retrieved, more nodes dissected and found by the pathologist survived better regardless of pathologic stage [nodes status] than those patients who had fewer in this case, than 10 nodes.” This shows the importance of having extended lymph node dissection when having a radical cystectomy, especially for those whose blc is locally advanced with a high probabilty of (or known to have) metastases. I think this presentation is good for all people to read before having cystectomy because it does stress the need to have a surgeon highly experienced in radical cystectomy surgery and discusses what comprises good surgery. I know some that have requested an extended lymph node resection and their surgeon only performed a limited one. Which just means it is hard to convince some doctors to change their normal way of doing things. But, armed with information such as this presentation gives you, I cannot help but think it would help convince the surgeon of the seriousness of your request.

The full text article of the Southweat Oncology Groups reasearch paper that Herr references in his presentation can be found:

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer[lxi]

I realize that cystectomy for metastatic bladder cancer is not the usual course of action in England. However, I do not understand their stance on this for those that have a complete response to chemotherapy.

Hope this helps,
Linda W
P. S. Another aspect of good surgery that Herr mentions is clean margins. I think it would be advisable for all scheduling a radical cystectomy to discuss with their doctor the possibility of not being able to achieve clean margins and what the options would be if this is the case. When clean margins cannot be obtained in this surgery, it is usually in the area of the ureters or the urethra. When it is the urethra, the remedy is urethra removal and a diversion other than a neobladder. However, when it is the ureter, its removal also means the loss of the kidney it connects to which is a serious decision. Personally, I would want the surgeon to know that I wanted to be completely free of cancer even if it meant the loss of a kidney. I would not want to go through this complicated of a surgery only to have to still have cancer that had to be treated or removed along with the kidney at a later date. With all the miraculous feats the medical profession performs, I do not know why there is not a substitute for a ureter. Do any of you know why it is always necessary to take the kidney when the ureter needs to be removed?

A Population Based Assessment of Perioperative Mortality After Cystectomy for Bladder Cancer[lxii]

Wednesday, 10 June 2009

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.

Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction.

We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries.

At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy.

The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

Written by: Isbarn H, Jeldres C, Zini L, Perrotte P, Baillargeon-Gagne S, Capitanio U, Shariat SF, Arjane P, Saad F, McCormack M, Valiquette L, Peloquin F, Duclos A, Montorsi F, Graefen M, Karakiewicz PI.

Reference: J Urol. 2009 May 16. Epub ahead of print. doi:10.1016/j.juro.2009.02.120

PubMed Abstract PMID:19447427

Twenty-Year Experience of Radical Cystectomy for Bladder Cancer in a Medium-Volume Centre[lxiii]

Friday, 05 June 2009

To evaluate long-term survival after radical cystectomy (RC) for bladder cancer (BC) and to define risk factors for BC-specific death.

Patients having RC for BC with curative intent in Turku University Hospital 1986-2005 were assessed. Survival results were recorded and 10 risk factors for BC-specific death were analysed.

In total, 248 patients with a median age of 64 years were included in the study. Sixty-four per cent of the tumours were intravesical and the lymph-node metastasis rate was 9%. Disease recurrence was observed in 90 patients (36%). Median time for local recurrence and distant metastasis after RC was 9 and 12 months, respectively. The mortality rate for both local recurrence and distant metastasis was 93%. Upper urinary tract and urethral recurrences were less common (3% and 5%, respectively) and occurred later (median time to recurrence 26 and 18 months, respectively). The 5-, 10-, and 15-year BC-specific survival was 69%, 67% and 66%, respectively. Extravesical tumour status, high tumour grade, positive node status and no history of intravesical therapy before RC were significant risk factors for BC-specific death. Other variables (neoadjuvant radiation, lymphadenectomy, age, time period, gender, smoking) did not affect the risk.

The survival results are comparable with those of high-volume centres and demonstrate the possibility of excellent local control in all cases and a high rate of cure in tumours confined to the bladder. Extravesical tumour growth, high grade and lymph-node metastasis are the most important risk factors for BC-specific mortality.

Written by: Bostrom PJ, Mirtti T, Kossi J, Laato M, Nurmi M.

Reference: Scand J Urol Nephrol. 2009 May 8:1-8. Epub ahead of print.

PubMed Abstract PMID:19424935

Impact of Treatment Delay in Patients with Bladder Cancer Managed with Partial Cystectomy in Quebec[lxiv]

Thursday, 04 June 2009

Department of Surgery (Urology), McGill University, Montréal, Que.

Treatment delays have been associated with adverse outcomes in patients with bladder cancer treated with radical cystectomy (RC). We sought to evaluate the impact of treatment delay on disease recurrence and survival in patients with bladder cancer treated with partial cystectomy (PC) in Quebec.

We reviewed and obtained billing records for all patients who underwent PC and/or RC for bladder cancer in Quebec between 1983 and 2005. Analysis included age, sex, year of surgery, surgeon’s age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of death.

A total of 714 patients underwent PC. The median patient age was 70 years. Two-hundred nineteen (30.7%) patients experienced recurrence; of these, 52 (23.7%) required salvage RC. Five-year overall and recurrence-free survival for patients who underwent PC were 49.8% and 40.3%, respectively. Patients delayed more than 12 weeks from transurethral resection of bladder tumours (TURBT) to PC were at significantly increased risk of requiring salvage RC compared with those delayed 12 weeks or less (hazard ratio [HR] 3.0, p < 0.001). Patients who underwent salvage RC had worse survival than patients who had upfront RC (HR 1.5, p = 0.006). Variables including age, sex, presence of hematuria, intravesical therapy, surgeon age, hospital PC volume, surgeon PC volume, type of hospital (academic v. nonacademic) or year of surgery were not significantly associated with PC treatment delay.

Treatment delay in patients with bladder cancer managed with PC was associated with increased risk of salvage RC. Patients with bladder cancer who underwent salvage RC had worse outcomes than those who had upfront cystectomy.

Written by: Fahmy N, Aprikian A, Al-Otaibi M, Tanguay S, Steinberg J, Jeyaganth S, Amin M, Kassouf W.

Reference:  Can Urol Assoc J. 2009 Apr;3(2):131-5.

PubMed Abstract PMID:19424467

The Risk Factor for Urethral Recurrence after Radical Cystectomy in Patients with Transitional Cell Carcinoma of the Bladder

Kang Su Cho^a, Joo Wan Seo^a, Sung Jin Park^a, Young Hoon Lee^a, Young Deuk Choi^a, Nam Hoon Cho^b, Seung Choul Yang^a, Sung Joon Hong^a

^aDepartment of Urology and Urological Science Institute, and
^bDepartment of Pathology, Yonsei University College of Medicine, Seoul, Korea

Address of Corresponding Author

Urol Int 2009;82:306-311 (DOI: 10.1159/000209363)

Purpose: We evaluated the incidence and risk factors for urethral recurrence following radical cystectomy and urinary diversion in transitional cell carcinoma. Patients and Methods: A retrospective review was performed of the 412 consecutive patients who underwent radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder between 1986 and 2004. A total of 294 patients were enrolled in this study. We investigated the impact of various clinical and pathological features on urethral recurrence by univariate and multivariate analysis. Results: Urethral recurrence developed in 13 patients (4.4%) and the 5-year urethral recurrence-free probability was 94.9%. On univariate analysis, positive urethral margin, prostatic stromal invasion, and prostatic urethral involvement had a significant influence on urethral recurrence (p < 0.05). The other clinical and pathological features were not significantly associated with urethral recurrence (p > 0.05). A multivariate Cox proportional hazard model revealed that a positive urethral margin (hazards ratio (HR) = 18.33, p < 0.001), prostatic urethral involvement (HR = 7.95, p < 0.001), and prostatic stromal invasion (HR = 5.80, p = 0.018) were independent risk factors for urethral recurrence. Conclusion: A positive urethral margin is considered an absolute indication for prophylactic urethrectomy. In addition, more careful patient selection is necessary for orthotopic urinary diversion in patients with prostatic urethral involvement and prostatic stromal invasion.

Copyright © 2009 S. Karger AG, Basel

Sung Joon Hong, MD, PhD
Department of Urology
Yonsei University College of Medicine
134 Shinchon-dong, Seodaemun-gu, Seoul (Korea)
Tel. +82 2 2228 2315, Fax +82 2 312 2538, E-Mail sjhong346@yuhs.ac

==================================================

05/04/2009 18:49

Hi Wendy,

Thanks for all that info and your concern – as always, much appreciated. Oh, and I don’t mind your bluntness at all.

Perhaps I should clear one or two things up. When I said I’d not had my bladder out ‘cos there was no point, I was quoting four oncologists and a urological surgeon – and, at the time, this seemed reasonable. It was only when I read that so many of the USA patients still had RC that I realised this may not necessarily be the right thing; hence my queries/contributions. I am now seriously considering it.

However, there are several cautionary factors. Let me share them:

1. It is not certain how much mets I have – initially I wasn’t thought to have any; then, only in the lymph nodes (and one contributor here implied that wasn’t the most serious mets).

2. Cisplatin based chemo seems relatively new, and seems to work much better than the older MVAC; indeed, maybe the MVAC didn’t enhance longevity at all.

3. All my 5 tumour marker tests have come back within the normal range so far.

4. The research you quote is based on only 14 patients, and only half of those who had primary bladder tumours (mine), one of which died. There’s no mention of any who didn’t have RC as a comparison, unlike the other research I was pointed to by Linda (where 40% who didn’t have RC survived 5 years).

5. My nodes seem all to be quiescent now.

6. Things are improving all the time, and indeed may already be much better but we won’t know for years – the UK’s top expert had said (18 months ago) that I had a 5% chance of remission with chemo; now the figures are up to 40% +.

7. If (I know, a big IF, but not unreasonable) improvements continue with such treatments, and with adjuvant CAM, I have a fair basis of hope.

8. Bear in mind that 2.2% die having the surgery, and 30% suffer painful complications.

So I appreciate your strong recommendation for RC, and acknowledge that it there is supportive evidence – but not, to my mind, overwhelming (given what I say above).

Hence I will continue my wait and see policy.

At the moment, I am symptom free; returned to apparent good health (doing my exercises – walking, jogging, weights; weight and muscle-mass OK; etc).

But I will continue my research; be diligent; listen to others’ experience.

Kind regards, Ian

 

Chemo-surgery yields 92% survival in metastatic TCC‏

From:    Wendy Ramsay (ramsaycafe@COMCAST.NET)

Sent: 05 April 2009 16:54:17

Ian,

 

I can't find the working link to this article so here is a copy

(below). Hopefully now you know now that the opinions of your doctor "I've not had my bladder out, 'cos I was told there was no point - being diagnosed as metastatic, the cancer had already spread and so there was no point." Are wrong. That statement is very disturbing.

 

Here is an article that you may want to consider. After reading this

article, I flew to MDAnderson and spoke with Randall Millikan about this procedure for myself. Dr. Millikan was the point person for their study, very intelligent and agressive if the patient is willing and able. I send this to you because you said you have remnants of a lymph node that did not completely respond..."I don't really want to wait until there's a clear symptom of the recurrence - at present the only ones suggested is a noticable enlargement of my supraclavicular lymph node or repeated CT scans (which I've declined 'cos of the heavy X-Ray loading)." I considered this surgery for myself to remove a supraclavicular node(s) on my collarbone.

Because I responded completely to chemo and the node(s) disappeared, I was not a candidate for this surgery.

 

I hate to say this, but if you have an untreated met, I don't think

you should be worrying about x-ray loading. The met will kill you - not the x-ray(s). You seem very intelligent but to be more worried about x-rays than an existing met is dumbfounding.

 

Please forgive me - I don't mean to be rude - but as much as I respect the rights of people to choose what they want, your reasoning seems like a death sentence to me. I'm sorry for the bluntness but something's not right.

I hope I am as wrong as wrong can be.

 

Good luck, Ian.

 

 

Chemo-surgery yields 92% survival in metastatic TCC "Homburg, Germany-A combined approach of chemotherapy and surgical resection is not only feasible, it may be preferable to chemotherapy alone in some patients with advanced urothelial cancer, German researchers report.

 

The dual-modality treatment yielded a 3-year tumor-specific survival

rate of 92% and an overall survival rate of 85% in a cohort of 14 patients.

 

"We found that, if we treat patients with distant lymph node

metastasis with inductive chemotherapy and see a response, then often these lesions are resectable," said Marcus Hack, MD, a urologic fellow working with Michael Stöckle, MD, at Saarland University Hospital in Homburg. "These patients had a very good prognosis after surgical resection of their metastasis-better than treatment with just chemotherapy."

 

The caveat, Dr. Hack said, is that the treatment is probably suited

only for certain types of patients, and selection criteria have yet to be developed.

 

"It's difficult to say which patients would benefit most from this

approach, but I suspect that it may be patients with sole metastasis and small-volume metastasis who would show good response to the inductive chemotherapy," Dr. Hack said.

 

'New approach in urology' The 14 patients in the study were evenly

divided between those with primary bladder tumors and those with

upper-urinary-tract tumors. All but two underwent resection of their primary tumor before diagnosis of distant metastasis. The others had concurrent metastasectomy with cystectomy.

 

The site of metastasis was the distant lymph nodes in 11 patients and

the lungs in three others, while one patient also had metastatic disease in an adrenal gland.

 

Five patients received gemcitabine-based chemotherapy (Gemzar) to

optimal response as pre-emptive treatment before metastasectomy. The other nine had received adjuvant chemotherapy for their resected primary tumors, and seven underwent additional chemotherapy after metastasectomy.

 

Tumor recurrence was observed in three of the 14 patients at mean

follow-up of 19 months, starting from the time of diagnosis of metastatic disease. Chemotherapy and surgery were reapplied in one of those patients and were well tolerated.

 

In all, three patients died during the course of the study. One death

was tumor-related, while two died of other causes.

 

"This is a new approach in urology," Dr. Hack said at the AUA annual

meeting. "If you have metastasis, normally you would use palliative

chemotherapy and then stop treatment. Now some groups are trying to resect this metastasis in patients who respond to inductive chemotherapy."

 

One such group is at the University of Texas M.D. Anderson Cancer

Center in Houston. Researchers there examined 31 patients with metastatic urothelial cancer who underwent surgery after undergoing chemotherapy. They found that the median survival from time of metastasectomy was 23 months, and the 5-year survival rate was 33%, suggesting that resection may contribute to long-term disease control when integrated with chemotherapy."

 

Wendy Ramsay

====================================================================

 

22/03/2009 17:51

Thanks to Linda leading me to a superb summary of the recent (2008) research into muscle-invasive bladder cancer and the various ways of treating it, I’ve got a better handle on the various options and likely success outcomes. Here is my take on that work (please correct me if I’ve got it wrong).

 

Linda (and others) was quite right: it is better to have RC.

 

However, there are a few caveats:

 

1. there is a risk of the surgery itself: 2.2% die;

 

2. a third who have RC have bad post-surgery complications

 

3. neo-adjuvant chemo (must be cisplatin based) should be done (that is, first) – it’s not nearly as effective if done afterwards (adjuvant); those with low BRCA1 genes have less response to chemo.

 

4. for best results, more than 10 nodes should be taken out too

 

5. even when the neo-adjuvant chemo appears to have led to a cure (no clinical signs of cancer), subsequent pathological checks show that actuall about a third did indeed have cancer still

 

6. However, IF there is no apparent cancer (cytoscopy, etc), or ureteral obstruction, there had been a small solitary tumour, the sugery had apparently removed all the cancerousness, and no sign of cancer in the prostate, then it isn’t too unreasonably to hold off doing an RC.

 

7. There’s some confusion (for me), but it appears that those who have chemo, RC & radiation have 66% complete remission; 5-year Survival whether RC or not, is 53%; and keeping the bladder (non-RC) 43%. That seems to me to mean that having chemo, RC & radiation gives a 50% improved survival (66% vs. 43%) over non-RC. But the reporter emphasised that this distinction is not as clear as it looks – perhaps ‘cos neo-adjuvant cisplatin is too new to have enough data yet. He says that retention of one’s bladder is a viable option.

 

8. If the bladder is to remain, then there must be a complete removal of the tumour, followed by chemo, and then radiation. And be prepared to go to RC if there’s any sign of resurgence.

 

Ian

=====================================================================

21/03/2009 22:28

Hi Linda,

 

Nope, not mind at all.

 

Don’t worry; I’ll not be pushed.

 

Re T4 + seemingly complete remission giving a possible viable option for retaining one’s bladder: The theory seems to be simple:  mets is treated differently to non-mets – by systemic chemo; so maybe there’s no more cancer; if it has previously escaped, it’s now gone; if it hasn’t, then it’s as liable to pop up anywhere as in the bladder; so keep watch and deal with whatever pops up – which may not be in the bladder any more.

 

However, for less serous cancer, there seems to be evidence that it’s still lurking in the lining of the bladder; systemic chemo hasn’t been used.

 

And anyway, I’m only quoting what the video said. Presumably the presenter knew what he was talking about. So if we take his comments on the other stuff, it seems reasonable to take it on this too.

 

There’s the added complication in the UK, in that this RC + neo-bladder is less common; so less experienced surgeons avaible to do it. Surgery itself carries a 2% risk of death. Add all that up, and it is less a straight choice that it is in the USA.

 

But I fully take on board your emphasis on insisting on the best surgeon available in the UK, etc.

 

Thanks again for your good wishes. I in my turn hope things continue to go well with you.

 

Kind regards, Ian

Ian/articles‏

From:    lweyand@aol.com

Sent: 21 March 2009 21:47:21

To:    ianclements@HOTMAIL.COM

Hi, Ian,
Hope you do not mind my writing directly to you instead of through the List. I am glad that you found the ASCO articles either interesting or informative. Also, I am hoping that you do not feel that I am pushing you in one direction or the other. I really meant it when I said that I do not expect you to see things as I do or make the decisions that I would make and that I respect the challenges and decisions you are facing.

In your most recent post, you said, “Whilst this generally supports that view that for most, an RC is best, one point at the end stands out: if there are a lot of favourable conditions, that saving the bladder is a viable option – just needs lots of monitoring.”

I realize this may be the position taken in the presentation, but it just does not make any logical sense to me that if for muscle invasive T2 , T3, and local N+(after neoadjuvant chemo) RC/urinary diversion is either the standard of care or has proven to provide better long-term results, then with complete response to chemotherapy for T4N+M+, how could saving the bladder ever be a viable option, no matter how much monitoring. If you have been so fortunate to have eliminated the mets why wouldn’t it be best to remove the original source of those mets. I am not saying that I know the experts are wrong, just that it makes absolutely no sense to me.

In one of your previous post on March 16th in reply to a post from Wendy R. you wrote:
=0 A”I’m just quite apprehensive about having RC, with or without the neobladder that seems the best, along with probably losing my sex life.” I hope you do not mind my addressing the sexual effects of radical cystectomy that men have to come to terms with when deciding to have an RC. Sometimes, but far from usually, surgeons are able to perform nerve sparing surgery which offers a better chance, but not a guarantee, that erections will still be possible. When successful, it usually takes a good bit of time for everything to return to normal/almost normal working order and sometimes requires an ED drug such as viagra. However, with your hope of the surgery giving you a cure and depending on where your tumors were/are located, nerve sparing may not be advisable. I should note that the removal of pelvic lymph nodes are reported to have nothing to do with these sexual after effects, it is just the RC itself. However, something that I was surprised to learn and most men do not realize unless a doctor is kind enough to point it out early in the cystectomy discussion, radical cystectomy does NOT affect the ability to have an orgasm, even though, without nerve sparing, it does affect the ability to have an erection. There are methods that men can then use that makes it possible to have sexual intercourse without natural erections such as penile injections or penile implants. Men on our List have reported good results with these methods, some referring one method, others another method. Apparently, different nerves are involved in orgasms than in erections, but I never knew this until being taught differently. Since some of the men on our List were glad to learn this, I thought I would pass it on just in case your doctor has yet to discuss this with you.

I also want you know that my life with a neobladder is no different than my life before. I can lift extremely heavy objects, take part in any sport if I chose to, travel to anywhere I please, etc. My urinary diversion imposes no physical limitations on my life. I do have to get up in the middle of the night to void, but I did that before the surgery, too. It really seems that it makes no difference which of the diversions a person choses because they soon adapt to their new normal. Now, people appear to be more satisfied with the internal catherizable pouch or the neobladder, but there are plenty of people living a wonderful life with ileal conduits(stoma/outside bag–these bags have an opening that fits over a stoma on the abdomen and do not attach to the thigh like Foley catheters do).

As I pointed out to Jan in a recent post, GOOD surgery can make all the difference in the outcome for people with bladder cancer, especially those with T3 and T4 disease. Dr. Herr gave a presentation at ASCO several annual meeting ago where he took the position that some of the good results of neoadjuvant chemo/cystectomy that M. D. Anderson was touting were from the patients having had good surgery=2 0at the time of cystectomy just as much as it could be attributed to the neoadjuvant chemo. If I were you and decided to opt for RC  then I would try my hardest to make sure the surgeon understands that I was seeking a cure (no matter how unlikely the medical proffession thought that to be) and that I wanted extremely GOOD, very thorough surgery with extended lymph node dissection.
I would keep Karen Greene’s and Hildegard’s stories foremost in my mind and strive for the same results.

I hope you soon recover from you chest infection and wish you peace of mind in whatever decision you make.

My best to you,
Linda W. neobladder 2/2002

====================================================================

21/03/2009 19:24

Hi Linda,

 

Thanks for taking the trouble to help me to get to grip with whether to have an RC or not. I’ve spent a good chunk of today viewing the three references – alas, only the last one was on target, tho’ the other two were of interest.

 

Your ref, specifically the third one (http://media.asco.org/player/default.aspx?LectureID=1091&conferenceFolder=am2008&SessionFolder=01075&TrackID=N929&LectureTitle=What%20is%20state%20of%20the%20art%20for%20surgery%20and%20peri-operative%20chemotherapy%3f&Key=vm_55_3_39_1091&SpeakerName=Speaker%3a%20Dean%20F.%20Bajorin%2c%20MD&mediaURL=%2fmedia&ServerName=media.asco.org&max=47&ext=jpg&useASX=false&playtype=windows) does address my concerns explicitly – so for that an even greater thank you.

 

Whilst this generally supports that view that for most, an RC is best, one point at the end stands out: if there are a lot of favourable conditions, that saving the bladder is a viable option – just needs lots of monitoring.

 

I’ll be sending this to my oncologists – after I’ve viewed it again a couple of times and summarised it (and get over what I hope is just a nasty chest infection).

 

I do not expect anyone or set of figures to decide for me, but it helps my decision if I have figures relating to similar actions.

 

As far as I can see, many of the figures being used on this site, without, often, any references (so making it hard to follow up) relate to those who did not have mets – and so these do not help me.

 

The few figures I had managed to dig up, for those with mets and who have RC, are seemingly in conflict. So your one helps a bunch.

 

Kind regards, Ian

 

Date:               Sat, 21 Mar 2009 00:45:00 -0400

From:             Linda Weyand <lweyand@AOL.COM>

Subject:   Re: Ian/articles

Hi, Ian, I doubt that you will ever find any research that will tell you to have the RC because you will be guaranteed to live longer if you do. However, I have read enough to believe that if I had metastatic bladder cancer my chances of living longer would be increased by having a radical cystectomy and extended lymphadectomy. This increase is not guaranteed and it is not by a huge percentage, but it sure looks better to me than not having it done. I realize that some of this is based on the reports that show surgery after chemo, even with a complete response, is necessary for long-term survival in advanced N+M0 cancer

Since the present standard of care for metastatic bladder cancer has a prognosis that is very unfavorable, I would be wanting to go beyond the standard of care. And, if I had a complete response to chemo like you appear to have had, I would be looking for all the avenues that might defy the standard of care prognosis. Whether it be another chemo regimen or RC with extended lymph node dissection, or any other medical treatment that a doctor here or in Europe or Asia or elsewhere was using to try to improve survival. I would attack the cancer from every front possible, using Wendy Ramsay as my role model.

Please understand, this is just the way I would feel about it, and I do not expect you to feel the same way. I have deep respect for the challenges you are facing and the decisions that you are having to wrestle with.Â

Today I f ound a series of presentations at the 2008 ASCO Annual Meeting (American Society of Clinical Oncology). These presentations are available as video and slides. The video will both show and explain the slides so that is what I recommend anyone interested to view. The three presentations are: 1) Novel agents and strategies: What does the future hold?  by Cora M. Sternberg, MD 2) Lessons learned from studies of chemotherapy in advanced TCC  by Christopher Sweeney, MBBS 3) What is state of the art for surgery and peri-operative chemotherapy? by Dean F. Bajorin, MD http://tinyurl.com/dz8f79

Wishing you the best, Linda W. neobladder 2/2002

Date:               Fri, 20 Mar 2009 21:53:32 -0400

From:              Ruth Mary Pollack <rmpollack@COMCAST.NET>

Subject:   Re: RC or not RC

Linda W

I want to compliment and underscore the two detailed and informative emails that you have contributed. If anything, it has been my experience these last 6 or so years on the BLC Cafe that people try and tend to be conservative in their advice, never interfering with medical opinions but educating and sharing when appropriate. My assessment is that overall there is sometimes too much encouragement and not enough hard ball. Bladder Cancer is a dangerous and deadly disease. Medical science is trying to find ways to cope and cure but still, too many people lose the battle.

Recently I had an appointment with a urology specialist at Yale assessing my yearly CT scan results. My RC took place five years ago. During our conversation, he made some stunning comments that I will share. Since I had gone through a year or so of BCG treatments, surgical removal of tumors and every three month close watching by the surgeon, this urologist asked me what precipitated my choice to have an RC. His comment was sad. He said the hardest part of his job is to convince people when the time has come, that their bladder needed to go. Then he gave me statistics: Non invasive, with an RC we have an 85% chance of being around five years later. With muscle invasion, he said our chances drop to 50%, and with lymph involvement down to 20%. Then he concluded: People hang on to their bladders too long.

Ruth Mary

Hi Linda,

Thanks for all those references.

Maybe I haven’t read them right, but when I looked at all of the articles, non of them seemed to have any evidence that doing RC was better than not doing it.

One was just assertive, not evidence based.

The others were investigating what happened to those who had RC, not comparing them with those who didn’t have it.

If I’ve misunderstood, my apologies. Maybe I was wrong to expect something different, along the lines that of comparing two similar groups, one had RC and the other didn’t – and the one that had RC lived longer.

Ian

=========================================================

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy.[lxv]

Yu RJ, Stein JP, Cai J, Miranda G, Groshen S, Skinner DG.

Department of Urology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, USA.

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.

(I.C.: This does not compare those who had RC with those who hadn’t)

PMID: 16813876 [PubMed – indexed for MEDLINE]

Radical cystectomy in the treatment of bladder cancer always in due time?[lxvi]

 

May M, Braun KP, Richter W, Helke C, Vogler H, Hoschke B, Siegsmund M.

Urologische Klinik, Carl-Thiem-Klinikum Cottbus, Lehrkrankenhaus der Universitätsklinik Charité zu Berlin, 03048, Cottbus. M.May@ctk.de

INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.

PMID: 17676301 [PubMed – indexed for MEDLINE]

(I.C. There is no comparison with a similar group who did not have RD, so of little use)

Radical cystectomy for bladder cancer: the case for early intervention.[lxvii]

Chang SS, Cookson MS.

Department of Urologic Surgery, Vanderbilt University Medical Center, A-1302 Medical Center North, Nashville, TN 37232-2765, USA. sam.chang@vanderbilt.edu

There are no prospective studies comparing early cystectomy versus cystectomy after failed conservative management in patients with high-risk superficial bladder cancer. In the absence of clinically proven biomarkers for predicting tumor biology and the response to therapy, the treatment decision must be individualized based on the high-risk features outlined herein. Assuming that all patients can be treated effectively with bladder-sparing regimens and safely salvaged at the time of failure or progression is dangerous. Data support the negative impact of a delay in cystectomy and argue for improvements in the timing of cystectomy despite the clinical absence of muscle invasion. Accordingly, high-risk patients with non-muscle invasive disease require vigilant follow-up and should be informed from the onset of the risk for progression and the possible need for cystectomy. Repeat resection before intravesical therapy in the patient with T1 tumor is advised and should help to improve, but will not completely eliminate, the problem of clinical under-staging. Among patients with CIS and recurrent high-grade non-muscle invasive tumors, repeat biopsies following intravesical therapy are encouraged to ensure treatment response. Although there is debate regarding the timing of early cystectomy for patients with high-risk non-muscle invasive bladder cancer, there is little doubt that, for muscle invasive disease, prompt cystectomy influences the effectiveness of this therapy choice. An unnecessary delay in the performance of radical cystectomy in patients with organ-confined bladder cancer compromises outcomes and risks potentially avoidable deaths from disease.

(I.C.: This is just assertion, not evidence. Phrases like “little doubt” begs the question)

PMID: 15862612 [PubMed – indexed for MEDLINE]

Related Articles

• [Radical cystectomy in the treatment of bladder cancer always in due time?] [Urologe A. 2007]
• Cystectomy in patients with high risk superficial bladder tumors who fail intravesical BCG therapy: pre-cystectomy prostate involvement as a prognostic factor. [Eur Urol. 2005]
• Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy. [J Urol. 2006]
• ReviewInvasive T1 bladder cancer: indications and rationale for radical cystectomy. [BJU Int. 2008]
• ReviewThe best treatment for high-grade T1 bladder cancer is cystectomy. [Urol Oncol. 2007]

=====================================================

Radical cystectomy for bladder cancer: the case for early intervention.

Urol Clin North Am 2005 May;32(2):147-55

“…. Assuming that all patients can be treated effectively with bladder-sparing regimens and safely salvaged at the time of failure or progression is dangerous. Data support the negative impact of a delay in cystectomy and argue for improvements in the timing of cystectomy despite the clinical absence of muscle invasion. …. Although there is debate regarding the timing of early cystectomy for patients with high-risk non-muscle invasive bladder cancer, there is little doubt that, for muscle invasive disease, prompt cystectomy influences the effectiveness of this therapy choice. An unnecessary delay in the performance of radical cystectomy in patients with organ-confined bladder cancer compromises outcomes and risks potentially avoidable deaths from disease.” ?http://tinyurl.com/dz9xa8

The following paper is listed as a comment and you really need to have the full text for the full review. This comment is by the late John Stein one of the most repected and exceptional bladder cancer surgeon we?have ever had?in the United States. I hold much faith in his opinions as well as his data supported research. Please note that unlike the way we normally view invasive as meaning into the muscle, this article refers to invasive T1 because it has invaded the lamina propria. I have read other papers where the authors felt that invasion into the lamina propria meant that T1 should be categorized with invasive disease, not superficial. ? Invasive T1 bladder cancer: indications and rationale for radical cystectomy. BJU Int. 2008 Aug;102(3):270-5. Epub 2008 May 20

“Invasive T1 bladder cancers are potentially lethal tumours with varying degrees of aggressiveness and progression. The management of invasive tumours can be very difficult and includes bladder-sparing with transurethral resection and intravesical therapy, or a more aggressive approach with radical cystectomy. Certain clinical and pathological factors might provide some risk stratification for invasive T1 tumours, and might better direct the physician towards an earlier cystectomy for some patients. This review provides a rationale for a radical cystectomy in patients with high-risk, invasive T1 bladder cancer.” http://tinyurl.com/c5xvxa

Drs. Herr, Donat, and Dalbagni?at MSKC have an article that you might find informative since your restaging TURB showed no cancer cells: Can restaging transurethral resection of T1 bladder cancer select patients for immediate cystectomy? J Urol. 2007 Jul;178(1):352.[comment] ?and 2007 Jan;177(1):75-9; discussion 79.[for the review]

“PURPOSE: We determined whether pathological findings on restaging transurethral resection predict early stage progression of T1 bladder cancer. MATERIALS AND METHODS: A cohort of 352 patients presenting with T1 bladder cancer on initial transurethral resection was evaluated by second or restaging transurethral resection. All patients received bacillus Calmette-Guerin therapy and 88% were followed for 5 years. Pathological findings on restaging transurethral resection were correlated with tumor features, stage progression frequency and progression-free survival. RESULTS: Of the 352 patients with T1 tumors 203 (58%) had residual tumor on restaging transurethral resection, including 92 (26%) with residual nonmuscle invasive (T1) cancer. During 5 years 66% of cases recurred and 35% progressed in stage. Of the 92 patients with residual T1 cancer 75 (82%) progressed to muscle invasion within 5 years compared to 49 of 260 (19%) who had no or nonT1 tumor detected on restaging transurethral resection. CONCLUSIONS: Restaging transurethral resection identifies patients with T1 bladder cancer who are at high risk for early tumor progression, justifying immediate cystectomy.” http://tinyurl.com/dfqxzz

Although I do not have the articles available to link to you, I know that Dr. Montie at University of Michigan has also written papers concerning surveillance and early cystectomy.

I got the above articles from pubmed.gov at the following link, and the site is well worth searching if you have interest in the latest research: http://www.ncbi.nlm.nih.gov/pubmed/ ===========================================================

20/03/2009 15:40

Hi Dave,

Seems we agree re medical help in differing countries after all.

The case for RC is muddier than I thought and than the initial contributions showed.

Clearly many who write have lived quite a while with their RC and so are not unreasonably in favour. Alas, these are the survivors – not much better than anecdotal evidence (not to dismiss that – such evidence is a necessary preliminary to doing deeper research) – and we don’t know what percentage that is of all those who’ve had it.

Dave’s high quote of 86% survival (vs. 35% not having RC) may relate to those with low grade tumours, but nothing in the research I’ve seen so far supports that. I fear it may be an over-exuberant consultant trying to convince a nervous patient (no doubt sincerely, perhaps believing it him/herself).

At 72 myself, I perhaps ought to be more relaxed that my end may be nigh, but you won’t be surprised to hear that I’m not.

Yes, the group is good. I’ve been following it for a while (I was diagnosed about 17 months ago), but only recently joined in – partly ‘cos I couldn’t get the forum to work for me, partly ‘cos I was just hesitant.

Kind regards, Ian

David Simms (d.e.simms@sbcglobal.net)

Sent:

20 March 2009 15:25:55

By the way, I was T1G3+CIS when after eight years of dealing with
superficial high grade disease, I decided to have Cystectomy. At 52 years
old now, two years out from Cystectomy (with neo bladder), life is pretty
much normal for me.

As a result of where I live, I self referred myself to UCSF, where I was
fortunate enough to come under the care of Dr. Konety. A Google search will
reveal more about him. I like the fact that he was so knowledgeable of all
aspects of the disease and knew the percentages of success and lack of for
all of my questions.

=============================================================

19/03/2009 14:04

To RC or not to RC?

Following up Karen’s very helpful listing of the research that implied having RC after successful chemo helped long-term survival, I’ve now spent a bit of time analysing that summary – and am confused by the actual data reported – admittedly only a summary. This confusion has been added to by a later report (see later) which appears to contradict it. Perhaps colleagues here can help me?

In the 2001 research into post-chemo (cisplatin) metastatic patients (such as myself), there were 207 initially.

80 had RC afterwards.

24 of these seemed clear of cancer (as I do).

14 of these ‘survived’ 9 months to 5 years after the RC – so did 10 die before that? And none after 5 years?

Of those 49 who had some evidence of cancer still, and also had the RC, 20 ‘survived’ – more than 5 years? So did 29 die in less than 5 years?

The authors then say that “only 1 of the 12 patients who refused surgery remains alive” – presumably after more than 5 years. But where did that 12 come from? It must have been from the 127 who didn’t have surgery. But why report on only 12 of those? What about the other 115 of the 127 who didn’t have RC?

And of the 80, it seems the 7 (80 less the 24 + 49) who had no response to chemo died early.

There’s no report on the survival of the 127 really apart from the 12 who refused RC. Perhaps they survived at a similar rate.

Of the 80, 34 at most survived more than 9 months; perhaps few survived more than 5 years.

So if the authors use living 9 months or more as success, I wonder how many of the 127 who didn’t have RC lived 9 months and thus did as well?

Have I read all that right?

Now, perhaps contrary to this, there’s a report this year (http://www.cancerpage.com/news/article.asp?id=13193) which implies that RC for T4 is not effective: the authors, having surveyed all stages of bladder cancer, conclude “earlier cystectomy or other aggressive therapy can save the lives of some patients with nonmuscle-invasive disease.” – implying that this isn’t true for muscle-invasive bladder cancer. All this implies to me that the case for RC for metastatic bladder cancer is still not proven as being an advantage. Or have I misunderstood?

Ian

18/03/2009 15:13Thanks for those suggestions Karen, but I hope you will forgive me if I don’t read those. I too agree on the mind-body interconnection, and have done NLP and PNI, aromatherapy and EFT. I think they’ve helped.

Perhaps because I’m scientific/engineering oriented, I have also do a lot of supplements and nutritional stuff, plus exercise and oxygenation.

For me, the best books I came across (of many that impressed) are those of Jonathan Chamberlain:

“Cancer: The Complete Recover Guide”, and his shorter

“Cancer Recovery Guide – 15 alternative and complementary strategies for restoring health”.

Chris Woolams “The Rainbow Diet and how it can help you beat cancer” & “Everything You Need to Know to Help You Beat Cancer” give supportive info.

There’s so much out there (including Borks 2001 “Natural Compounds in Cancer Therapy” and Alschuler & Gazella’s “Definitive Guide to Cancer”).

So I’ve read myself to a stop on books just now, having ploughed through another dozen or so on top of those. Nowadays, it is mainly the ‘net & analysing my own data (I measure everything I do – weight, exercise, etc).

As well as all the pills I take, I’ve re-oriented my nutrition to drive my body’s pH (as reflected in my urine) to be more alkaline. I’m not too sure of the soundness of the underlying theory, but what it does do is guide me to eat far more veggies and fresh fruit and less carbohydrates (plus no sugar or alcohol).

Kind regards, Ian

RE: THE article‏

From:    Karen Greene (rpkjg01@omh.state.ny.us)

Sent: 18 March 2009 14:55:47

To:    Ian Clements (ianclements@hotmail.com)

Despite all that I have written, I am a firm believer in the mind-body connection, and did a lot of alternate /complimentary stuff along with my medical treatment. I wanted to do everything medically, but also got my brain engaged.

 

Check out the following books:

 

L. LeShan Cancer as a Turning Point Carl Simonton et al, Getting well Again Hirshberg & Barasch Remarkable Recovery Fanning Visualizations for Change [the section on immune diseases]

J. Borysenko - Power of the Mind to Heal and Full catastrophe Living-- along with J. Kabatt-Zinn

 

Let me know what you think. K

18/03/2009 14:08

Thanks for that Karen.

What is slowly dawning on me is that really not much is known about how metastatis happens.

There is the view, clearly prevalent here in the UK, that once the cancer cells have started wandering, they are then self-perpetuating at whatever site they alight.

However, the implication of the USA practice of removing the bladder (and being successful) is that this would otherwise remain a source of triggering of the metastatic cells’ growth, despite their having gotten out there – not something I’d considered before (and which, I suspect, will be at odds with the UK guys ideas).

A support to the USA idea is that it is not clear why different initial cancer sites give rise to differing metastatic daughter sites (such as bladder going to the supraclavicular lymph node, liver, and lungs – rather than, say, the prostate, stomach, and heart). So with so much ignorance about how metastasis happens, one goes with the evidence, not the theory. RC =  longer survival, never mind why.

Kind regards, Ian

RE: THE article‏

From:    Karen Greene (rpkjg01@omh.state.ny.us)

Sent: 18 March 2009 13:10:30

To:    Ian Clements (ianclements@hotmail.com)

Hi Ian-- it is a tough call. The thing we have to be aware of is that

all mets start as cancer cells [microscopic level] wandering through the body and nesting somewhere. And it only takes one or two to start the cascade of tumor development somewhere else. Also-- re the recurrence issue, the same conditions which were the occasion for the development of the original cancer may still pertain [genetics, environmental stress, etc]. Obviously, the stats are not 100%-- so there is always the chance of being in long term remission-- but the odds are not in your favor. Aggressive monitoring is helpful, but ultimately the decision is yours. There is life after the RC-- as you have heard from everyone who weighed in on this-- but even this is not 100% as we have lost a few people even after the RC. Go with your gut and do your part to have a healthy life, and keep reading so you are informed. If you can get to a medical library, do a search for other articles by those authors-- they are all prolific researchers and doing good research into bladder cancer survival. Karen

===========================================================

17/03/2009 22:35

Many thanks Karen.

Whilst it is a bit disheartening to me, as I have the fond illusion that if I’m in remission and all my cancer markers remain within normal + my scans don’t show anything, then I’m OK. Repeating this every few months, and finding the same, then I can slowly resume a ‘normal’ life – albeit now on a different nutritional regime (which I give some credit to to having come through this, as well as the major reason being the chemo).

I’ll have to stew on this; talk it over with my oncologist. As you won’t be surprised to hear, I really don’t want to do the RC, but, as you and others point out, if it is fairly certain that not doing it is a death sentence and doing it gives a good % chance of survival, then it’s a no-brainer.

Kind regards, Ian

From:    Karen Greene (rpkjg01@omh.state.ny.us)

Sent: 17 March 2009 18:21:23

To:    ianclements@hotmail.com

Hi Ian,

I finally found it-- the reference and abstract are below. My memory of the numbers was wrong-- but having the cystectomy after chemo significantly improved survival. 

 

On the personal note-- my mets was in the nodes way up into my trunk, not limited to around the bladder or pelvis-- and remission of the mets was shown on the progressive CTS. My surgeon [Donat above] reported an 80+% recurrence rate if the bladder remained; the guy at Columbia I went to for a second opinion state that there was a 100% rate of recurrence. So I went ahead and here I am 9 + years later. Hope this helps and that you can find a talented surgeon! Karen

 

 

48. 

Herr HW. Donat SM. Bajorin DF. Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer. Journal of Urology. 165(3):811-4, 2001 Mar. 

Click the "Ovid Full Text" link. 

UI: 11176475 PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.

==========================================================

17/03/2009 14:53

Thanks Roni.

However, I am still totally bewildered by the BCC navigation. I haven’t been able to use the Webcafe’s home page. There seemed to be three different entry points, one of which (if my memory is right) which was defunct; the other confused me; and now I get all this via listserv.acor.org – it always work, so I’m (lazily) just using that.

But enough. I must sort this out!

Ian

Re: [CAFE] metastatic blc/RC‏

From:    Rolsen64@aol.com

Sent: 17 March 2009 14:43:21

To:    ianclements@HOTMAIL.COM

Hi again Ian,

Yesterday I sent an article on urinary diversion options to you.  RC is understandably a daunting procedure.

If you go to Webcafe’s home page – upper right corner, click on Resources.  It will take you to Resources USA.  Then  scroll way down to Recommended Reading, you’ll find my book, “A Guide to Bladder Cancer, Urostomy and Impotence.”  Wendy and Joris have made it available in pdf format. You can either read it online or print anything of interest.   It covers most everything related to bladder cancer, and has 2 chapters on impotence and penile prostheses.  Ben has had an inflatable prosthesis since 1985 – comfortable, unobtrusive, easy to use and works great!  Hopefully you won’t need to know any of it and will qualify for nerve-sparing.

Also, happy to answer questions e-mail or phone.

Best,

Roni      ===========================================================17/03/2009 14:31

Thanks Wendy. That improves the picture for me.

On reflection, my oncologist did mention that things had moved on in the last few years, especially re chemo.

It may be that I need to watch the various cancer markers before deciding anything, along with the scans.

I also recall that RC was originally ruled out ‘cos the lymph nodes either side of my bladder were so enlarged and pressing on nerves that it would be difficult/impossible to remove them. Having said that, I suspect they’ve now reduced to normal.

Ian

Date:               Tue, 17 Mar 2009 15:16:04 +0100

From:              Wendy Sheridan <wendy@BLCWEBCAFE.ORG>

Subject:          Re: cystectomy a guarantee??

There is a small but real chance of a recurrence post-cystectomy of cancer elsewhere but the stats say that risk is low, about 10%. There seems to be increased risk with CIS and, logically, the recur rate increases with stage and grade of the Cx specimen.

Some experts absolutely feel the need to remove the bladder post-chemo if response was good, some obviously not.

Neoadjuvant chemo seems to becoming more and more popular in the literature and clinical trials but other experts will say that post-op is just as helpful and only use it in case of extravesical spread.

There’s also a bit of a difference between Europe or the UK and the US, with the opinion leaning to: “America doctors are more aggressive in just about every way” (not a direct quote but something I have gleaned from numerous urology conferences in Europe). Which may explain Ian’s doctor’s recommendations.

I doubt a doctor would knowing operate if there is obvious nodal involvement but it can happen that this is only discovered perioperatively. In which case it is something a person should discuss before the operation. How much spread is too much, according to the doctor, to finish the operation? Ideally spread is limited to a node, or a couple…and surgery is completed.

The stats for those who have aborted cystectomies and given chemo and no more surgery are pretty dismal.

The opinion of late seems to be toward chemo for all invasive blc, while ten years ago that was not the case, we saw many more stage IIIA and IIIB-ers having no chemo. I know a few who did fine, too, no recurs and ten years down the road!

I heard two esteemed experts dispute the famous USC/Stein paper Dan Martin mentions recommending extended lymph node removal. The debate was enlightening, basically the “con” side (delived by a UK expert, with the ‘pro’ side coming from a German expert) said that the patient population used in that paper was rather skewed, using many Pa and P1 specimens giving it all a brighter outcome than most situations would stand to gain.

Please note I’m not arguing with USC and Stein’s approach of removing many nodes-it seems too successful for me to argue! Just that there are many differences of opinion between experts, though guidelines are finally being established between the AUA and the EUA these days…However, the guidelines do not recommend 65 nodes-I think it’s more in the neighborhood of 10!

The option of surgery post-chemo might also depend on other factors, such as extent of original spread, area of spread, health of the person and personal choice. If a doctor is following standard procedure he can’t be blamed but the guidelines are flexible and ideally a doctor should be, too (not to mention the insurance involved).

Wendy

=============================================================

Date:               Tue, 17 Mar 2009 08:44:11 -0400

From:             H Mayer <hildegard_mayer@HOTMAIL.COM>

Subject:          Re: metastatic blc/RC

Here is my bl.c. history: Diagnosed in 1999: A large through-the-bladder-wall tumor blocked the ureter which damaged my kidney severely. After 3 Taxol and Carboplatin chemo treatments, I learned during a consultation at a TX cancer center that my tumor did not shrink. Had a RC with ileal conduit 5+ months after my diagnosis (4 of 8 checked lymph nodes were cancerous). A PET scan found numerous new cancerous nodes in 2000, some in inoperable places. A MSKCC expert recommended to my small town oncologist (then my 4th) for me: Gemzar and Adriamycin chemos. A PET scan showed after 2 or 3 treatments the shrinkage of the nodes and after 4 or 5 no more cancer, but I finished all 6 treatments. It was not an easy journey (misdiagnosed for a long time; later was told: 6 to 11 or 12 months with or without RC or chemos, even “Go home and do what you still want to do.” A lot of luck was on my side: a surgeon who still did the RC; a PET scan that found during an unrelated hospital stay the metastasized nodes while a CT scan report from that month mentioned no new cancer; my last oncologist; the MSKCC doctor for the perfect for me chemo recommendation; last, but not least – this great support group. I did not even know that bladder cancer existed when I was diagnosed. The information and support I received from many list members was priceless. Please keep in mind that the treatments that I received may or may not work for others with advanced bl. c., since we are all different. I agree with Linda: A PET scan can be very helpful for us with advanced bladder cancer. My surgeon said that he wished that I would have had a PET scan before the RC. Medicare and some insurance companies do not pay for a PET scan for even advanced bladder cancer patients without a bladder. I heard of a very recent study by MSKCC, but did not see it in print, about PET scan and bladder cancer. Did someone? The suggestion to see the best expert is good, but my insurance would only pay for in-state consultation, treatment or surgery, even that there were only 3 (to 5) female RCs done in the whole small state in a year. A 2nd and 3rd opinion doctor visit was important to me for my treatment decision. How I wish that all of you can in 10 years and in good health write their follow-up note to the group. Good luck, Hildegard P.S.: Congratulations to all that had recently a “milestone”. ==========================================================

17/03/2009 13:04

Thanks Mike; that gives me some comfort and confidence to explore this alterantive.

Ian

Date:               Tue, 17 Mar 2009 08:30:45 -0400

Ian –

Whatever you decided to do there are now nerve sparing surgery techniques that can spare the sex life. I fully understand your concern, I had the same and it had prompted me give the CM a try.

Another factor for me was that I had once had a several week impotence problem brought on by medication. I knew from that experience that not having the ability had absolutely no effect on the desire.

Good luck on finding a surgeon that can spare your necessary nerves.

Mike

=========================================================

17/03/2009 09:31

Thanks for that elaboration Wendy. Not only am I not fatalistic (well,most of the time – I do have my dark moments), but fortunately neither is my wife. So I think I can give it a good shot.

I’m just quite apprehensive about having RC, with or without the neobladder that seems the best, along with probably loosing my sex life.

But the great support and info from this forum is helping me no end.

Ian

Date:               Mon, 16 Mar 2009 17:59:13 -0700

Ian, I’m not sure how your medical system differs but I searched hard before my RC not only to find the best surgeons, but equally important was to find doctors that were willing to fight with me. A mutual understanding of how I wanted to approach my treatment (in my case, the most aggressive approach) was necessary. There are great differences in attitude amongst doctors. Fortunately, I found one in particular (Dr. Kaplan) that was willing to give it his all right along side me. I consulted with others that advised me on the most aggressive approaches possible in my case….all in the ‘chance’ and ‘hope’ for cure and against the odds. People do survive.

I couldn’t afford a fatalistic attitude and I couldn’t afford any of my medical team to have one. Can you consult with other doctors? Maybe there is someone willing to help you that can show some optimism. Hope is tangible and affects our recovery.

Wendy Ramsay

Voiding with a neobladder…6 hours..Wow! A normal night for me is 1 and a half to 2 and a half hours before having to void…I am up 3 to 5 times a night. Dr. Grossman at M.D. Anderson told me that I need to set the clock for every two hours. Sometimes I do and sometimes I don’t..and sometimes I am really glad that someone invented Adult Depends, because I hit the snooze button and doze back off. I think that some folks have the neobladder done with the large intestine and some with small intestines…don’t know that for a fact but could be. But, those of us who can go for 6 hours must have a larger capacity than I do, that’s for sure. I have tried a couple of alternative devices but they tend to slide off while I am sleeping, so I have opted, for the moment, just to use Depends (and hope they don’t leak…and they do sometimes, too) Just sleep with a pad under me, and do the best that I can.

Bill Pullen Houston, Tx.

Date:               Mon, 16 Mar 2009 17:07:58 -0700

Dr. Stein removed my stage III bladder along with 65 nodes in January 2006. He found no evidence that it had spread to the nodes, but since cells can sometimes remain undetected, I go in for my check ups every 6 months. Diana =============================================================

16/03/2009 23:46

Great Dan; that looks really convincing – just hope (a) it works on my oncologists; (b) I can suss out an experienced urological surgeon in the specialism. I fear that, given my oncologists opinions, that there may not be too many in the UK doing such work.

Kind regards, Ian

Date:             Mon, 16 Mar 2009 19:37:03 -0400

Linda and Ian and Robert…

The ‘classic’ USC Norris journal article (by Stein and Skinner…) of 1,054 bladder cancer patients included 244 patients that had lymph node positive disease. 209 had more than 15 nodes removed and 35 had less than 15 nodes removed.

Recurrence-free survival was about 45% for the group that had more lymph nodes removed and about 20% for the group that had fewer nodes removed. See figure 6. I’m happy to send the article to anyone who wants it.

Equally important, these patients were followed for up to 15 years and the data clearly shows that the ‘C’ word (cure) can be used after about 4 or 5 years (unlike bladder sparing therapies where recurrence continues over time – this is not an anecdotal (one person hey look at me) but a statistically valid conclusion based on a large population of patients).

This shows that even for those patients whose cancer has metastasized, RC with extended lymph node removal can be a worthwhile option.

I was one of those who travelled a significant distance (350 miles) for my RC (65 nodes removed); almost 5 years later I would take the same approach, absolutely no second thoughts.

And even if my blc were to recur, at least I’d bite the big one knowing that I took my best shot.

So for those who have high-grade cancer, I agree with Silverman that a proactive and aggressive approach can save your hiney (at least until the Grim Reaper comes by for that last visit).

Dan ===========================================================

16/03/2009 23:41

Thanks Roni for that full description of the alternatives. This will help me if I decide I need to go down that route.

Alas, it still doesn’t sound too good – but as someone said, it beats the alternative.

Kind regards, Ian

Urinary diversion options‏

From:    Rolsen64@aol.com

Sent: 16 March 2009 23:22:22

To:    ianclements@HOTMAIL.COM

Hi Ian,

In response to your inquiry about urinary diversions – all are workable/doable – and all better than the alternative.  My article on urinary diversion options follows:

Best of luck and big hugs,

Roni

===========================================================

16/03/2009 23:30

OK; will do. But the info you’ve given me is probably enough for now. This certainly makes me less worried about having RC.

Ian

Date:               Mon, 16 Mar 2009 19:01:47 -0400

please read about the alternatives– there is a link on the site. There are 3 options– the external appliance– on the abdomen rather than the leg– that is for immediately aftr surgery. Then there is the catheterizable internal continent reservoir which I have, and then the neobladder– which is a bladder replacement constructive of bowel tissue and which is connected to your original issue urethra. Karen =============================================================16/03/2009 23:26

Much appreciated Karen. I hope you can find it.

Ian

16 March 2009 23:14:48

To: BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

I will look some more tomorrow-- I recall the name of one of the

authors-- H. Herr, but the other authors were surgeons or fellows at

Sloan Kettering and it was a major journal. Will look some more. I

recall it convinced me I made the right decision so it must have been

after 2000. Karen

===================================================

16/03/2009 23:07

Thanks for that illumination Mitch; that sounds much more aesthetically acceptable.

Regards, Ian

Mon, 16 Mar 2009 22:59:26 +0000

Ian,

A neobladder is an internal bladder made from some part of your small or large intestine.  The ureters and urethra are attached to the bladder.  You pretty much void the same way, through the same plumbing, but bear down to empty the bladder.  Think of what you did as a kid when you wanted to ‘pee fast”.

I’ve had a neobladder since May 2004 with no major problems.  I’m fully continent during the day, 99% continent at night, and had a surgeon skilled in nerve sparing techniques.  Its a good option for those who are eligible for it.

Mitch

16/03/2009 23:03

Jolene,

I agree about Linda’s good info. And others. It is making me do a re-think about RC.

However, I was just saying that the link you gave  me isn’t relevant to my case – I’m collating as much info as I can to share with my oncologists with a view to seeing what is available here (probably meaning I’ll have to make a strong case, given what appears to be the standard view that RC is of no use at my state of cancer).

Thanks again,

Ian

16 March 2009 22:55:14

To:  BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

Ian --

 

Linda sent good info to you. My husband also was node positive but we

didn't find that out until surgery. He is now 7-1/2 yrs. from neobladder surgery which was followed w/4 cyles of MVAC chemo. His surgeon also removed numerous lymph nodes and pathology confirmed one node was positive for TCC. At the time, his prognosis for survival was 25% without chemo and 50/50 if he had chemo so we feel very fortunate. Also, life with a neobladder is about like normal with the exception of having to get up at least once during the night to void.

 

Good luck with your decision --

 

Jolene

[CAFE] metastatic blc/RC‏

From:	The Bladder Cancer Support and Information eCommunity (bladder-cancer-cafe@listserv.acor.org) on behalf of Linda Weyand (lweyand@AOL.COM)
Sent:	16 March 2009 22:05:08
To:	BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

Hi, Ian and Robert,
I know of two members of our List that had metastatic bladder cancer, had neoadjuvant chemotherapy, and subsequently had their bladders removed. Both have enjoyed long-term survival. One is Karen and her story can be found here:
http://blcwebcafe.org/content/view/41/29/lang,english/

The other is Hildegard and you could find info about her story by searching the bladder cancer cafe archives. If I remember correctly, most doctors had a fatalistic attitude toward her situation, and she had to fight like crazy to get the treatment that she wanted and needed.  After receiving the treatment she sought, her fatal prognosis became long-term survival…hooray! I think anyone considering an RC knowing they have/had node positive bladder cancer should have a pet scan immediately prior to surgery so that any lymph nodes that “light” up can be removed along with the bladder. In fact, I would want to go with USC’s protocol and have extensive lymph nodes resection. USC often removes 65+ nodes during RC whereas most surgeons elsewhere remove approx. 10-20.

Karen and Hildegard have remarkable and miraculous stories that may be of benefit to you.  (Hildegard: If I have misrepresented your story in anyway, I apologize….my memory is not what it use to be!)

Personally, if I had node positive bladder cancer and had received successful chemo, I would want an RC/urinary diversion with extensive lymph node resection. I would consult with one of the highly reputed bladder cancer surgeons even if it meant having to travel a great distance for the appointment. Although I think that your doctors are probably following the accepted standard of practice, in your situation I would want to go far beyond the accepted standard and take any logical step available in hopes of acheiving a long-term survival result….with our courageous Wendy R. as my role model. Many people and doctors think having your bladder removed is a last resort that needs to be avoided if at all possible, and it has been common practice to not remove the bladder in metastatic cases. I guess having had such a good life since my bladder was removed makes me see this is a completely different light. I do not have any research on hand that recommends RC with nodal involvement, so please remember this is just my gut feeling on this subject.n I am looking forward to reading Wendy R.’s take on this issue.

Hope this helps,
Linda W.

From:    The Bladder Cancer Support and Information eCommunity (bladder-cancer-cafe@listserv.acor.org) on behalf of Linda Weyand (lweyand@AOL.COM)

Sent: 16 March 2009 20:36:49

To:    BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

Hi, Lorraine,
People who receive neoadjuvant chemo prior to having their RC often have a complete response from the chemo treatment with no evidence of disease. These are the people Karen is writing about….they had neoadjuvant chemo, but no radiation.  In one research series that I am aware of, there was a 100% recurrence/fatality rate among those that opted to keep their bladders after the neoadjuvant chemo. I do not remember the statistics of those that had the RC after the chemo, but there was a much higher survival rate.

In no way does this relates to your situation because you had combined modalities (CM) not just neoadjuvant chemo. CM includes both radiation and chemo and is intended to result in the patient keeping their bladder. Of course, if a recurrence occurs after the CM treatment is completed, RC/urinary diversion is the next step to hopefully assure long-term survival. Recently, you mentioned that you had polyps removed….were these checked by pathology to determine if they were benign, atypical, or cancerous cells?

Hope this helps,
Linda W. neobladder 2/202

The Bladder Cancer Support and Information eCommunity (bladder-cancer-cafe@listserv.acor.org) on behalf of Shawhouse (shawhouse@EARTHLINK.NET)

Sent:

16 March 2009 19:08:26

To:

BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

USC doctors have the philosophy that the more nodes that are removed

during cysectory, the less likely there will be a spread to other areas outside of the urinary tract.

Diana

Re: [CAFE] cystectomy a guarantee??‏

From:    The Bladder Cancer Support and Information eCommunity (bladder-cancer-cafe@listserv.acor.org) on behalf of Karen Greene (greenegoddess1@JUNO.COM)

Sent: 16 March 2009 19:01:01

To:    BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG

Hi Ian- when I was diagnosed and treated 9 years ago - was told by 2 different docs at different hospitals that even tho I apparently had a complete response to the chemo, the bladder had to go since there is such a high rate of recurrence. There was an article which came out of MSKCC which showed that of a number of post chemo, none of those who refused the RC survived. Not all who had the RC didN but none of those who refused it. I can try to locate the reference if you like. Karen

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology[lxviii]

Accepted 2 July 2008. published online 21 July 2008.

Background

Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance.

Objective

We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology.

Design, setting, and participants

Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists.

Measurements

All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications.

Results and limitations

Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1–2 in 51% (n=582), and grade 3–5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%.

Conclusions

Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

Take Home Message

Accurate reporting of complications utilizing the 10 reporting criteria and methodology is essential for preoperative counseling, for identifying modifiable risk factors to reduce complication rates, for planning combined modality treatment, for clinical trial design, and for a more accurate assessment of surgical success.

Radical cystectomy for T2 bladder cancer with failed chemo[lxix][lxx]

Outcome after radical cystectomy in patients with clinical T2 bladder cancer in whom neoadjuvant chemotherapy has failed

ABSTRACT

To analyse the outcome after radical cystectomy (RC) in patients with clinical T2 bladder cancer not responding to neoadjuvant chemotherapy (NAC).

PATIENTS AND METHODS

In a retrospective analysis, study patients received NAC for clinical T2 disease before RC and a control group had RC for clinical T2 disease with no NAC. Patients treated with NAC were further grouped based on the pathological response; failure to respond was defined as ‘no change in T stage or a higher T stage in the RC specimen (≥pT2)’, and the relevant clinical and pathological data were analysed.

RESULTS

In all, 53 patients satisfied the inclusion criteria for the study group and 200 for the control group. In the study group 18 (34%) responded to NAC (group 1) of whom 11 (61%) were pT0 and seven (39%) pT1, and among the non-responders (group 2) 19 (54%) were pT3/pT4 and 16 (46%) were pT2; 16 (46%) patients in group 2 had lymph node metastasis. The mean follow-up was 26 months. In group 2, local recurrence occurred in six (17%) vs none in group 1. Seven patients (20%) in group 2 developed metastases, vs one (5%) in group 1 (P = 0.01). The 5-year disease-free survival was significantly lower for group 2 (40%) than group 1 (91%, P = 0.007) and the control group (67%, P = 0.04). There were 14 deaths from bladder cancer in group 2, vs one in group I (P = 0.01). The 5-year disease-specific survival was significantly lower for group 2 (52%) than group 1 (83%, P = 0.008) and the control group (70%, P = 0.001).

CONCLUSION

A lack of response to NAC is associated with a significantly higher local and distant recurrence, and with lower survival.

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer

Tuesday, 10 November 2009

Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer. We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval. We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for ‘never washing hands’ before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI. We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI. Written by: Thulin H, Steineck G, Kreicbergs U, Onelöv E, Ahlstrand C, Carringer M, Holmäng S, Ljungberg B, Malmström PU, Robinsson D, Wijkström H, Wiklund NP, Henningsohn L. Reference: BJU Int. 2009 Oct 23 doi:10.1111/j.1464-410X.2009.08909.x PubMed Abstract PMID:19863516

 
Radical Cystectomy versus Radical Radiotherapy[lxxi]

A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire.

Chahal R, Sundaram SK, Iddenden R, Forman DF, Weston PM, Harrison SC.

Department of Urology, Orchard House, Pinderfields and Pontefract NHS Trust,

Wakefield, West Yorkshire WF1 4DG, UK

.

OBJECTIVES: To study the morbidity of radical cystectomy and radical

radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments.

PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality

of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model.

 

CONCLUSIONS: This retrospective regional study shows that there is no

significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality.

Gastrointestinal complications were responsible for the majority of

complications. The clinical T stage, the sex and the ASA grade of the

patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.

Copyright 2003 Elsevier Science B.V

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[1] http://www.europeanurology.com/article/PIIS0302283808008609/abstract?rss=yes

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[lxx] Murugesan Manoharan, Devendar Katkoori, Thekke A. Kishore, Bruce Kava, Rakesh Singal* and Mark S. Soloway; Departments of Urology and  *Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA

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