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Ian Clements: ‘radical cystectomy alternatives’ research – for bladder cancer

Posted by Jonathan Chamberlain on April 21, 2011


See also my two cancer books – http://www.fightingcancer.com for details

Ian Clements ‘ Radical Cystectomy Alternatives’ Research

RC Alternatives

Contents

Arguments against organ preservation in patients with muscle invasive bladder cancer. 2

Trimodality treatment for bladder cancer: Does modern radiotherapy improve the end results?. 2

Drug May Be an Alternative to Cystectomy for BCG Failures. 3

Phase II Study Of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine In Muscle-Invasive Bladder Cancer. 3

Radiation plus gemcitabine might be as good as surgery for bladder cancer. 4

Improved method for RC?. 5

Update of clinical trial data for trimodality therapy. 5

Surgery not always necessary for bladder cancer patients. 6

Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). 6

Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation. 7

Robotic cystectomy: Is it ready for prime time?. 7

RC versus Alternatives. 8

Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. 8

Updated results of bladder-sparing trimodality approach for invasive bladder cancer, 9

Gemcitabine sensitizes invasive bladder tumors to radiation. 10

Quality of life assessment after concurrent chemoradiation for invasive bladder cancer. 10

Failure of bacille Calmette-Guérin in patients with high risk non-muscle-invasive bladder cancer unsuitable for radical cystectomy. 11

Organ-sparing strategies in the management of invasive bladder cancer. 12

Bladder Preservation in Octogenarians With Invasive Bladder Cancer. 12

Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients With Disseminated Nonseminomatous Germ Cell Tumors. 13

Total Cystectomy Versus Bladder Preservation Therapy for Locally Invasive Bladder Cancer. 14

Bladder-Sparing Therapy a Good Alternative. 14

An Alternative to Radical Cystectomy. 16

Conservative treatment of invasive bladder cancer. 16

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK. 17

Radiochemotherapy for bladder cancer. 18

Safety of active surveillance program for recurrent nonmuscle-invasive bladder carcinoma. 18

What happens to the patients with muscle-invasive bladder cancer who refuse cystectomy after neoadjuvant chemotherapy?. 19

Radical Cystectomy versus Radical Radiotherapy. 21

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

Trimodality treatment for bladder cancer: Does modern radiotherapy improve the end results?[i]

by Mohamed S. Zaghloul, MD Tue, 05 April 2011

BERKELEY, CA (UroToday.com) – Recent trimodality organ-preservation strategies combine maximal transurethral resection of bladder tumour (TURB), chemotherapy and radiation.

The rationale for performing TURB and radiation is to achieve local tumour control. Application of systemic chemotherapy, most commonly as cisplatin-based regimen, aims at the eradication of micro-metastasis and to act as radio-sensitizers. This role has been established in many diseases and several studies. Cisplatin-based chemotherapy in combination with radiotherapy, following TURB, results in a complete response rate of 50-81%.It is recommended and stressed upon that early cystectomy is performed in individuals who do not achieve a complete response following combination therapy. This will allow about 42-78% of patients to survive with an intact bladder at 3-5 years. A comparable long-term survival rate of 50-60% at 5 years’ follow-up is reported by both multimodality bladder-preserving trials and cystectomy series. Trimodality therapy has the advantage that about half of patients expected to survive with their native bladder intact. However, both therapeutic approaches have never been directly compared. It is worth noting that bladder-preserving multimodality strategy requires very close multidisciplinary co-operation and a high level of patient compliance. Even if a patient has shown a complete response to a multimodality bladder-preserving strategy, the bladder remains a potential source of recurrence, or new tumour appearance. Pathological complete remission at repeat TUR after the initial transurethral resection of the primary tumour, followed by chemotherapy in combination with radiotherapy, was identified as a prognostically important variable. However, even the latter patients are at a life-long risk of developing intravesical tumour recurrences with the need for meticulous surveillance. Despite the absence of such direct randomized trials comparing both modalities, trimodality treatment comprising maximal TURBT followed by different regimens of combined radiochemotherapy achieved comparable results to radical cystectomy in many trials.

With the application of modern radiotherapy, it is possible to safely deliver a high radiation dose, with the sensitizing effect of the concomitant chemotherapeutic agents. These variable regimens of radiochemotherapy were successful in achieving the goal of improved survival rates, with preservation of the native bladder. The clinical target volume (CTV) for irradiating the bladder should encompass the entire outer circumference of the bladder, any extravesical disease spread and any region deemed to be at risk of microscopic disease spread. It has also been extended to include the prostate and prostatic urethra in males or upper vagina in females. The pelvic nodal CTVs extend around external and internal iliac vessels. The external iliac CTV extends anteriorly to include the lateral external iliac nodes. The internal iliac CTV extends laterally to the pelvic sidewall. The contours around the external and internal iliac vessels are joined to create a single volume on each side of the pelvis, including the obturator nodes. The pre-sacral CTV extends anteriorly to the first and second sacral prominence. The planning tumor volume (PTV) margins are 5–10 mm according to the institutional policy of creating CTV–PTV margins. Partial bladder irradiation (bladder tumor with safety margin) may be used as a boost – either through intensity-modulated radiotherapy (IMRT) external beam or via brachytherapy. The partial bladder approach permitted the delivery of a considerably higher dose without increased toxicity. It is estimated that the tolerance of part of the bladder volume is higher than that of the organ as a whole, with tolerance doses estimated at 80 Gy for two-thirds of the bladder compared with 65 Gy for the whole organ.

Radiation uncertainties include set-up errors, patient movement, internal organ movement, and volume changes due to continuous bladder filling (both inter- and intrafraction). The advancement in treatment verification procedures in modern radiotherapy and the use of fiducial markers applied during TUR, reduces set-up errors, while adaptive radiotherapy could decrease the unnecessary irradiation of normal tissues by tracking bladder volume changes. In addition, new radiotherapeutic techniques, such as IMRT and volume-modulated radiotherapy (VMAT), permit dose escalation to the target without increasing the dose to the surrounding normal tissues. The value of this trimodality treatment depends upon the extent and adequacy of TURBT, the use of effective chemotherapeutic agents both as sensitizing and adjuvant agents for radiotherapy, and more importantly, upon the precise technique of irradiation to achieve the desired results. Ensuring target coverage may improve the tumor control probability by ensuring the target receives the intended dose, while reducing dose to critical normal tissues.

Urodynamic tests and quality of life (QoL) studies for long-term survivors treated with trimodality treatment showed that 75% were considered to have bladders with normal function. Furthermore, a questionnaire study revealed that 78.8% were ‘delighted’ or ‘pleased’ in terms of urinary function after trimodality conservative therapy. More than half of men had erections hard enough for intercourse and around 59% were satisfied with their sex life after conservative therapy. Sexual function was reported in 50% of men and 71% of women following bladder preservation. These rates compare favorably with a contemporary questionnaire-based study that reported 13% and 42% potency rate following radical surgery and nerve-sparing cystectomy, respectively.

Drug May Be an Alternative to Cystectomy for BCG Failures[ii]

Jody A. Charnow March 21, 2011

VIENNA—Mycobacterial cell wall DNA complex (MCC) may provide an alternative to cystectomy for patients with non-muscle invasive bladder cancer refractory to bacillus Calmette-Guérin (BCG) treatment, according to preliminary study findings.

Alvaro Morales, MD, of Queen’s University in Kingston, Ontario, Canada, and colleagues tested MCC in 129 Caucasian patients with non-muscle invasive bladder cancer who failed to respond to one or more courses of BCG. The treatment consisted of six weekly intravesical instillations of 8 mg MCC (induction), followed by three once-weekly instillations at three, six, 12, 18, and 24 months (maintenance). MCC has two modes of action: immune stimulation and direct anticancer activity.

Of the 129 patients, 95 (73.6%) were male. At study entry, 91 (70.5%) had carcinoma in situ and 38 (29.5%) had papillary tumors.

The overall one-year disease-free survival (DFS) rate was 25%, the researchers reported at the 26th Annual Congress of the European Association of Urology. The one-year DFS rate was 21.0% for patients with CIS tumors and 35.1% for those with papillary tumors. The treatment was well tolerated, and most adverse events were mild to moderate in intensity and few led to treatment discontinuation.

Dr. Morales’ group explained that patients with tumors refractory to BCG generally have a poor response to second-line therapies. Radical cystectomy, they noted, is the standard of care following BCG failure, but some patients refuse surgery or are not good surgical candidates.

The drug, which has the trademark name Urocidin, is being developed by Endo Pharmaceuticals, of Chadds Ford, Pa., and Bioniche Life Sciences, of Belleville, Ontario.

Phase II Study Of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine In Muscle-Invasive Bladder Cancer[iii]

Written by Lynda Coghlan    Monday, 07 February 2011 09:03

The Christie NHS Foundation Trust, Manchester, United Kingdom. The Royal Preston Hospital, Preston; Leicester Royal Infirmary, Leicester; and The Gray Institute for Radiation Oncology and Biology, Oxford, United Kingdom.

The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX).

Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival.

All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%.

Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.

Written by: Choudhury A, Swindell R, Logue JP, Elliott PA, Livsey JE, Wise M, Symonds P, Wylie JP, Ramani V, Sangar V, Lyons J, Bottomley I, McCaul D, Clarke NW, Kiltie AE, Cowan RA.

Reference: J Clin Oncol. 2011 Jan 4. Epub ahead of print. doi: 10.1200/JCO.2010.31.5721

PubMed Abstract PMID: 21205754

Radiation plus gemcitabine might be as good as surgery for bladder cancer[iv]

Radiation plus gemcitabine may be as good as cystectomy for muscle-invasive bladder cancer, a phase II study suggests.

“After radiotherapy and four cycles of gemcitabine, three-year cancer-specific survival was 82% and overall survival was 75%, the study investigators reported online January 4th in the Journal of Clinical Oncology.

“These results with gemcitabine and radiotherapy are as good as the best reported results of cystectomy, although ours is only a small group of selected patients,” said Dr. Richard Cowan, a consultant in Clinical Oncology at Christie Hospital in Manchester, England

Improved method for RC?[v]

“Hybrid laparoscopic endoscopic single-site surgery for radical cystoprostatectomy and orthotopic ileal neobladder: An initial experience of 12 cases

“Laparoscopic endoscopic single-site surgery (LESS) has recently emerged as an attempt to enhance cosmetic benefits and reduce morbidity; however, LESS for radical cystectomy is still not well established. Here we describe the technique of hybrid LESS for radical cystoprostatectomy and orthotopic ileal neobladder (RC-OIN), and evaluate its feasibility and safety.

“All operations were performed successfully without conversion to conventional laparoscopic radical cystectomy or open surgery. There was no perioperative mortality or port-related complications. The median operative time was 383 minutes. Median blood loss was 150 mL. A median of 25 lymph nodes were removed. Surgical margins were tumor free in all cases.

Hybrid LESS for RC-OIN is technically feasible with effects similar to those of conventional laparoscopic procedures. Further instrument and technique improvement are necessary to shorten operative time and reduce intraoperative difficulties.

 Update of clinical trial data for trimodality therapy[vi]

Written by Christopher P. Evans, MD

Monday, 13 December 2010

BETHESDA, MD USA (UroToday.com) – Tridmodel therapy includes maximal TURBT followed by XRET (40Gy) with chemotherapy, next is cystoscopic response evaluation, and if good response, then XRT for 24 Gy more.

In 348 patients treated at the Massachusetts General Hospital (where Dr. Efstathiou is a radiation oncologist) between 1986-2002, 10-year overall survival (OS) was 35% and disease-specific survival (DSS) was 59%. Ultimately cystectomy was necessary in 29%. There were very few cancer events after 5 years. Use of neoadjuvant chemotherapy did not impart any DSS or OS benefit. Their data showed that complete TURBT is essential to the outcome.

A trial called SPARE in the UK to compare surgery to trimodal therapy closed due to poor accrual. A UK trial comparing XRT alone vs. XRT plus MMC and 5-FU was recently reported. Early on there was no survival benefit, but for local-regional DFS there was benefit to the addition of chemo at 3 years. He touched on biomarkers predicting response, and Her-2 is one such that is stratifying patients for the addition of Herceptin. Another is MRE11 that predicts for CSS following radical radiotherapy for muscle invasive bladder cancer. QOL after XRT is critical and 78% have compliant bladders and 50% of men have maintained erectile function. Overall about 70% of trimodal patients retain their native bladder.

Surgery not always necessary for bladder cancer patients[vii]

October 05, 2010 / TAMPA, Fla. / Bladder cancer is the fifth most common cancer in the United States says Dr. Randy Heysek, founder of the Central Florida Cancer Institute. He says approximately 50,000 people are diagnosed with bladder malignancies each year. As a staff member at H.L. Moffitt Cancer Center and Research Institute, Dr. Heysek has the opportunity to teach resident physicians about treatment options for a variety of cancers, as he did before a group of radiation oncology residents about bladder cancer.

“I take my role at Moffitt seriously,” says Dr. Heysek. “I want to give cancer patients the best care and treatment possible. I also want to make sure the resident physicians learn as much as they can about the techniques and procedures being used.”

Currently, radical cystectomy is the common treatment for bladder cancer. The procedure removes the entire bladder, nearby lymph nodes, part of the urethra and nearby organs that may contain cancer cells. However, the surgery can reduce a patient’s sexual function. Dr. Heysek, a board-certified radiation oncologist, says there is a non-surgical alternative.

“Patients can receive a carefully administered radiation therapy with concomitant chemotherapy given daily over a seven week period,” he says. “The long term results reveal a very satisfactory bladder function following radiation and chemotherapy. A majority of patients are able to keep their own bladders, rather than having them removed or having an artificial bladder constructed.”

Dr. Heysek adds the use of this bladder conserving treatment requires close collaboration between the urologist, medical oncologist and radiation oncologist. He says this ensures perfect integration and timing.

Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC)[viii]

BJU International, 10/05/2010  Clinical Article

Colombo R et al. – The authors present long–term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin–C (MMC) randomly administered to patients with non–muscle–invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection. This is the first analysis of long–term follow–up of patients treated with intravesical thermochemotherapy. The high rate of patients who were tumour–free 10 years after treatment completion as well as the high rate of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long–term follow–up, even in patients with multiple tumours.

Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation[ix]

Monday, 04 October 2010

Departamento de Urología, Clínica Universidad de Navarra, Navarra, España.

To evaluate the response and the free-survival progression in patients diagnosed of invasive bladder cancer who have been treated with transurethral resection, chemotherapy and radiotherapy. This multimodal treatment is compared with a not random serie of patients treated by radical cistectomy.

Retrospective analysis of 43 cases of invasive bladder cancer treated with two schemes of bladder preservation between 1994-2007. They are compared with 145 cases treated with radical cistectomy in the same period of time. Pronostic variables included in the study are clinical stage, grade of differentiation, presence of ureteral obstruction, chemotherapy modality, radiotherapy doses and p53 and ki-67 expression.

Mean and median time are 51 and 39 months in patients with multimodal treatment. Complete response is achieved in 72% of cases treated with bladder preservation. Ureteral obstruction is a prognostic factor (OR: 7,3;p:0,02). 72% patients with complete response mantain it at the end of the study. None of analyzed variables are predictors of maintenance of the response. Survival rates with a intact bladder were 69±7% and 61±7% at three and five years. Radiotherapy doses greater than 60Gy (OR: 6,1; p<0,001) and the absence of ureteral obstruction (OR: 7,5; p<0,002) were pronostic variables. Free-survival in patients with complete response was 80±7% and 58±10% at three and five years. At the end of the study, 53,5% of patients had a intact bladder and free-disease.In the same period of time, 145 radical cistectomies were performed due to muscle invasive bladder cancer. Mean and median time in this group were 29 and 18 months respectively. Stadistical analysis reveals a worse clinical stage in the group of patients treated with multimodal treatment (p:0.01). Free-survival was 72±5% and 63±7% at 3 and 5 years in the group of radical cistectomies. There was not statistical significant differences between cistectomies and bladder preservation.

Patients treated with bladder preservation have a free-survival similar to those treated with radical cistectomy. Radiotherapy doses greater than 60Gy and absence of ureteral obstruction were free-survival prognostic variables.

Written by: Rincón Mayans A, Rosell Costa D, Zudaire Bergera JJ, Rioja Zuazu J, Barba Abad J, Tolosa Eizaguirre E, Romero Vargas L, Pascual Piedrola I.

Reference: Actas Urol Esp. 2010 Oct;34(9):775-80.

PubMed Abstract PMID: 20843454

Robotic cystectomy: Is it ready for prime time?[x]

Slide Presentation

RC versus Alternatives

Date: Mon, 13 Sep 2010 07:57:37 -0400
From: jmikemann@COMCAST.NET
Subject: Re: [CAFE] MIBC treated with TURB, Chemo & Radiation instead of RC
Ian -

Many doctors have been working with this for years and have published the results.

I read reports over ten years ago from Dr. Shipley of Harvard Medical School, and Mass General were reporting approximately equal
results from RC or multimodality.  This was my reasoning to go that route rather than an RC.

Note that my Uro who had recommended an RC disagrees with me.  He has only recently moved me to yearly checkups previously insisting on every six months for eleven years.  He told his assistant at my last check that “I had dodged a bullet” but (I?) disagree.  At the time I made the decision the long term statistics for the two approaches were similar and it has seemed to work out for me.

Mike
07:22 AM 9/13/2010, Ian Clements wrote:
This seemingly good outcome seems to me to have been prematurely assessed – only 4 weeks later. As there’s a lot of evidence of recurrence long after this period, it would be nice to see this being compared with RC for similar patients over a longer period.

Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer[xi]
BJU International, 09/13/2010

Maarouf AM et al. ­ In this prospective study, the authors includded 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection. These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy. Four weeks later, all cases had radiological and cystoscopical re­eevaluation. Complete responders were considered to be those patients who had no evidence of residual tumour.

Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer[xii]

Between 1995 and 2001, 63 patients were evaluated who declined to undergo a planned cystectomy, because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy.Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with overall survival.

Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of surviving patients had solitary, small, and low-stage invasive tumors completely resected, and 83% survived without relapses in the bladder.

Editorial Comment

In Northern America neoadjuvant chemotherapy before radical cystectomy became standard few years ago. What happens if patients (or their doctors, the medical oncologists who deliver chemotherapy) refuse radical cystectomy if a complete response is found in the bladder? This paper gives some very important answers.

The study group was well chosen with only patients having residual muscle-invasive tumors receiving neoadjuvant chemotherapy. After at least 85% of the planned four cycles of cisplatinum-based chemotherapy, complete clinical response and negative transurethral resection (TUR) of the primary tumor site, these patients were deemed complete responders and were evaluable for follow-up in this group.

The good news is that 64% of these patients survived at least 5 years and 54% of them with functioning bladders. The bad news is that 36% died of bladder cancer after a mean of 32 months. The survivors could be identified by their good prognostic factors, namely single (p < 0.001), or small tumor (p < 0.01), complete restaging TUR (p = 0.02), and noninvasive stage after relapse (p = 0.05). Thus patients with worse tumor features, despite responding completely to chemotherapy, should be strongly advised to undergo radical cystectomy at the earliest convenience.

Updated results of bladder-sparing trimodality approach for invasive bladder cancer[xiii],[xiv]

Received 15 December 2008;  revised 21 January 2009;  accepted 22 January 2009.

Purpose

To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS).

Materials and methods

Between 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity.

Results

The mean follow-up for the whole series was 54 months (range 9–156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade ≥2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532).

Conclusion

These data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders.

Gemcitabine sensitizes invasive bladder tumors to radiation[xv]

“Adding gemcitabine (Gemzar) to concurrent radiotherapy and cisplatinum in invasive bladder cancer could preserve the organ even when the tumor has invaded the muscle, according to French researchers. In their pilot study, they sought to determine the maximum tolerated dose of gemcitabine to use with the gold standard of cisplatinum + radiotherapy.

“The patients in the study received a diagnosis of urothelial invasive bladder cancer but without hydronephrosis or diffuse carcinoma in situ. The cancer stage was T2-T4a with negative nodes and no metastasis.

“…..  cystectomy is the gold standard for treatment of invasive bladder cancer, but because of a high morbidity rate, patients often opt for bladder preservation. With standard bladder preservation treatments, about 50% of patients have a functioning bladder at five years

“Seven of the nine patients who completed the experimental regimen were cancer-free with intact bladders at a median follow up of 24 months.

Quality of life assessment after concurrent chemoradiation for invasive bladder cancer[xvi]

To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial.

Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment.

Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52-79%) of patients. Overall survival was 36% (95% confidence interval, 23-49%) at 8 years for all patients, and 45% (28-61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6-36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months.

Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients.

Written by: Lagrange JL, Bascoul-Mollevi C, Geoffrois L, Beckendorf V, Ferrero JM, Joly F, Allouache N, Bachaud JM, Chevreau C, Kramar A, Chauvet B.

Reference: Int J Radiat Oncol Biol Phys. 2010 Apr 10. doi: 10.1016/j.ijrobp.2009.10.038

PubMed Abstract PMID: 20385453

Failure of bacille Calmette-Guérin in patients with high risk non-muscle-invasive bladder cancer unsuitable for radical cystectomy[xvii]

An update of available treatment options

Tuesday, 16 March 2010

Department of Urology, Royal Hallamshire Hospital, Sheffield, South Yorks, UK.

Academic Department of Urology of la Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, University Paris VI, Faculte de medicine Pierre et Marie Curie and Centre d’Etudes et de Recherche sur les pathologies prostatiques, France.

Although the accepted standard upon failing intravesical bacille Calmette-Guérin (BCG) in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) is radical cystectomy, there are some patients for whom this is not an option. We critically reviewed previous reports on the treatment possibilities available in such a clinical scenario. The options available can be categorized as chemotherapy, immunotherapy, device-assisted therapy and combined therapy. Combining new with established intravesical treatments seems to hold the most promise. Maintenance thermo-chemotherapy gives a reported 2-year disease-free survival rate of 50% and in small early-phase studies of intravesical gemcitabine administered in combination with mitomycin-C, tolerance and efficacy data would suggest the need for larger trials, given the early encouraging results. Electromotive mitomycin-C given sequentially with BCG might not only reduce the recurrence rate but also reduce progression and disease-specific mortality, although currently there is no trial in a specific population with ‘BCG failure’.

Written by:  Yates DR, Rouprêt M.

Reference: BJU Int. 2010 Mar 1. doi:10.1111/j.1464-410X.2010.09272.x

PubMed Abstract PMID:20201829

Organ-sparing strategies in the management of invasive bladder cancer[xviii]

Bladder cancer is the second most common genitourinary malignancy. Radical cystectomy and pelvic lymphadenectomy is the standard of care in the management of muscle-invasive bladder cancer. However, recently, bladder-preservation trials conducted by both single- and multi-institutional groups have gained momentum because of comparable survival and recurrence rates in select patients. While single-modality therapies have failed to provide adequate results, multimodal combination therapies consisting of a thorough transurethral resection with radiotherapy and concomitant chemotherapy have been promising. Careful patient selection, maximum transurethral resection of bladder tumor, cystoscopic evaluation of response with prompt salvage cystectomy for nonresponders and strict long-term follow-up for complete responders constitute the hallmarks of optimal bladder-preservation protocols. Advances in molecular-targeted therapy, chemotherapy and radiotherapy hold promise to improve survival and local control and decrease side effects and toxicity.

Bladder Preservation in Octogenarians With Invasive Bladder Cancer[xix]

Received 26 July 2009; accepted 15 October 2009. published online 17 December 2009.

Objectives

To analyze mortality and morbidity of octogenarians with newly diagnosed invasive transitional cell cancer (TCC) of the bladder who were managed without cystectomy.

Methods

Retrospective chart review of all patients with newly diagnosed invasive TCC (≥pT1) in the period of 1997-2007, who were 80 years or older at diagnosis.

Results

A total of 71 patients (86 + 4 years, mean + standard deviation [SD], pT1: n = 29; >pT2: n = 42) entered this analysis. In this geriatric population, treatment regimens were highly individualized. After transurethral resection, 61% of pT1-patients received bacillus Calmette-Guerin and 62% of those with >pT2-tumors external beam radiation. Mean overall survival (OS) of the entire cohort (n = 71) was 22 + 26 months for pT1-patients 34 + 33 versus 14 + 15 months for those with ≥pT2-tumors (P = .001). Mean cancer-specific survival was 58 months for pT1-patients and 11 months for ≥pT2-patients (P <.001). OS was correlated to tumor stage and the degree of mobility, to a lesser extent to the American Society of Anesthesiologists (ASA) score, and only marginally to chronologic age. Satisfactorily bladder function was preserved in 73%. pT1-patients spent 16% of their remaining life-span in the hospital compared with 23% for patients with >pT2-tumors.

Conclusions

OS in TCC is dependent on tumor stage, age, mobility, and comorbidities, and a risk-stratified management is necessary. Patients with pT1G3 tumor and low ASA score have satisfying OS with bladder preservation, but in patients with ≥pT2 and ASA 3-4 the prognosis is very bad. It remains questionable whether patients with tumor stages ≥pT2 and ASA 1-2 despite high age would benefit from radical cystectomy.

Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients With Disseminated Nonseminomatous Germ Cell Tumors[xx]

Is a Postchemotherapy Retroperitoneal Lymph Node Dissection Needed After Complete Remission?

Abstract

Purpose Controversy arises regarding the optimal management of patients with nonseminomatous germ cell tumor (NSGCT) who achieve a serologic and radiographic complete remission (CR) to systemic chemotherapy. Some authors recommend postchemotherapy retroperitoneal lymph node dissection (PC-RPLND), whereas others omit surgery and observe these patients. In an attempt to address this question, we report the long-term follow-up of patients treated at Indiana University who were observed without PC-RPLND.

Patients and Methods This is a retrospective analysis of patients with NSGCT who achieved a CR to first-line chemotherapy and were monitored without further therapy. CR was defined as normalization of serum tumor markers and resolution of radiographic disease (residual mass < 1 cm).

Results One hundred forty-one patients were identified. Five patients (4%) had less than 2 years of follow-up. After a median follow-up of 15.5 years, 12 patients (9%) experienced relapse. Of these 12 patients, eight patients currently have no evidence of disease (NED), and four patients died of disease. The estimated 15-year recurrence-free survival (RFS) and cancer-specific survival rates were 90% and 97%, respectively. The estimated 15-year RFS for good-risk patients (n = 109) versus intermediate- or poor-risk patients (n = 32) was 95% and 73% (P = .001), respectively. Six patients (4%) experienced recurrence in the retroperitoneum, of whom two patients died of disease. Five patients had late relapse (range, 3 to 13 years), including two patients in the retroperitoneum. All five patients currently have NED.

Conclusion Patients obtaining a CR after first-line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and potentially curable with further treatment.


Total Cystectomy Versus Bladder Preservation Therapy for Locally Invasive Bladder Cancer[xxi]

Effect of Combined Therapy Using Balloon-Occluded Arterial Infusion of Anticancer Agent and Hemodialysis With Concurrent Radiation

Objectives: We tested the usefulness of balloon-occluded arterial infusion (BOAI) of anticancer agent (cisplatin/gemcitabine), concomitant with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation [Osaka-Medical College (OMC)-regimen] in patients with locally advanced bladder cancer. The results were compared with those of cystectomy.

Methods: One hundred twenty-four patients were assigned to receive cystectomy (Gp1, n = 62) or OMC-regimen (Gp2, n = 62). In Gp2, patients besides undergoing complete response subsequently received secondary-BOAI with gemcitabine (1600 mg).

Results: In Gp1, 27 of 62 patients (43.5%) suffered disease recurrence, and more than half died within 1 year; the remainder died thereafter. The overall 5-, 10-, and 15-year survival rates were 53.8%, 46.0%, and 40.0%, respectively. In contrast, in Gp2, >70% of patients (44 of 62), especially >95% of patients with locally invasive tumors achieved complete response with no evidence of recurrent disease or metastasis after a mean follow-up of 163 (range, 32-736) weeks. At 14 years, overall survival was significantly improved at 79.7% (P = 0.015 vs. Gp1). Moreover, salvage therapy for secondary-BOAI with gemcitabine was effective in all 3 patients with T4 tumors or lymph node involvement, who showed stable disease (SD) after primary therapy with CDDP. No patients suffered Grade III or more severe toxicities.

Conclusion: OMC-regimen, a new strategy for patients with locally-invasive bladder cancer, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Bladder-Sparing Therapy a Good Alternative[xxii]

By Charles Bankhead, Staff Writer, MedPage Today
Published: November 05, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

CHICAGO — Organ-sparing multimodal therapy for invasive bladder cancer achieves survival comparable to that of radical cystectomy, but with better quality of life, according to a study reported here.

The combination of transurethral tumor resection, radiation therapy, and chemotherapy led to complete responses in 72% of patients. Disease-specific and overall survival at five, 10, and 15 years compared favorably with results from contemporary patient series of radical cystectomy.

“The results support the acceptance of modern bladder-sparing trimodality therapy for selected patients as a proven alternative to cystectomy,” Jason Efstathiou, MD, PhD, of Massachusetts General Hospital in Boston, said at the American Society of Radiation Oncology.

Action Points

  • Explain to patients that a bladder-preserving therapy for invasive bladder cancer appears to attain results similar to those of radical surgery in selected patients.
  • Note that the findings came from a retrospective review of data from a single institution.
  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

“The optimal regimen of combined chemoradiation, as well as the addition of rational molecular targeted therapy, continues to be investigated.”

The findings came from an analysis of long-term follow-up data in 343 patients with muscle-invasive bladder cancer treated with trimodal therapy. The patients were treated from 1986 to 2002.

Treatment began with a 40-Gy dose of radiotherapy, followed by repeat biopsy and urinary cytology. Patients who achieved a complete response or who were not candidates for cystectomy received boost chemoradiation to 64 or 65 Gy.

Subsequently, 102 patients underwent radical cystectomy, 60 of whom did not have a complete response and 42 because of tumor recurrence.

The patients had a five-year overall survival of 52% and disease-specific survival of 64%. The rates at 10 years were 35% and 59% for overall and disease-specific survival, respectively, and 22% and 57% at 15 years.

“Eighty percent of patients who were alive at five years still had their native bladders,” said Efstathiou.

Among patients who had cystectomy, five-year overall survival was 29%. Survival was similar in patients who underwent immediate or delayed cystectomy.

The completeness of transurethral resection of the bladder tumor significantly influenced the likelihood of response and patient survival.

The 227 patients who underwent complete tumor resection had a complete response rate of 79%, decreasing to 57% for patients with incomplete resection (P<0.001). Overall survival at five years was 57% with complete resection and 43% without (P=0.003).

Disease-specific survival was 68% with complete tumor resection and 56% without (P=0.03).

In multivariate analyses, independent predictors of survival were complete response to induction therapy (HR 0.62, P=0.013) and low clinical T stage (HR 0.66, P=0.018).

For comparison, Efstathiou reviewed five- and 10-year overall survival with cystectomy reported from the University of Southern California in Los Angeles, Memorial Sloan-Kettering Cancer Center in New York, and the Southwest Oncology Group.

Five-year survival ranged between 36% and 49%, while 10-year survival was 27% to 32%. The five-year results at Massachusetts General were slightly better but still consistent with data from other studies of chemoradiation therapy for invasive bladder cancer.

As previously reported, a subset of 221 patients had urodynamics evaluations and completed a quality-of-life questionnaire. The results showed that 78% of the patients had compliant bladders with normal capacity and flow parameters, 85% had occasional or no urinary urgency, and 50% of the male patients reported normal erectile function (J Urol 2003; 170: 1772-76).

Data on a subset of 157 patients with bladder preservation who were followed for a median 5.2 years showed a 22% incidence of grade 1 late pelvic toxicity, 10% grade 2, and 7% grade 3 (J Clin Oncol 2009; 27: 4055-61).

Efstathiou had no disclosures.

Primary source: American Society for Radiation Oncology
Source reference:
Efstathiou J, et al “15-year outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the long-term MGH experience” ASTRO 2009; Abstract 21

An Alternative to Radical Cystectomy[xxiii]

September 18, 2009

Bladder-sparing treatment in which brachytherapy is added to external beam radiotherapy (EBRT) may be a valuable alternative for bladder cancer patients who refuse radical cystectomy or who are poor candidates for major surgery, according to researchers.

J.L.H. Ruud Bosch, MD, of University Medical Center Utrecht in the Netherlands, and colleagues reviewed data from 111 patients with solitary T1-T2 bladder tumors (5 cm or less in size). After undergoing transurethral resection of the tumors, patients were treated first with EBRT and then brachytherapy with iridium-192 at a dose of 40 Gy. A partial cystectomy was performed in nine patients, of whom five had a T3 tumor.

The study population had a mean follow-up of 6.2 years.

At the last follow-up, 75 patients were alive without evidence of disease and 17 had died without evidence of disease, the investigators reported in European Urology (2009;56:113-122). Nineteen patients died of bladder cancer after a mean follow-up of 2.9 years.

Overall survival rates at five, 10, and 15 years were 70%, 55%, and 51%, respectively. Disease-specific survival rates were 82%, 73%, and 73%, respectively. Disease-free survival rates were 60%, 47%, and 23%. Patients with T3 tumors had a nearly 20-fold increased risk of dying from bladder cancer. Additionally, 27% of patients experienced local recurrence and 9% underwent salvage cystectomy. Bladder function was preserved in 99 patients (89%).

From the September 2009 Issue of Renal And Urology News

Conservative treatment of invasive bladder cancer[xxiv]

Tuesday, 01 September 2009

Department of Radiation Oncology, McGill University Health Centre, Montreal, QC.

The concept of organ-preserving therapies is a trend in modern oncology, and several tumour types are now treated in this fashion. Trimodality therapy consisting of as thorough a transurethral resection of the bladder tumour as is judged safe, followed by concomitant chemoradiation therapy, is emerging as an attractive alternative for bladder preservation in selected patients with muscle-invasive bladder cancer. Long-term data from multiple institutional and cooperative group studies have shown that this approach is safe and effective and that it provides patients with the opportunity to maintain an intact and functional bladder with a survival rate similar to that for modern radical cystectomy.

Written by: Rene NJ, Cury FB, Souhami L.

Reference: Curr Oncol. 2009 Aug;16(4):36-47.

PubMed Abstract PMID:19672423

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK[xxv]

Monday, 31 August 2009

Department of Urology, Mid Yorkshire NHS Trust, Pinderfields Hospital, Aberford Road, Wakefield.

We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival.

The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variables on overall survival.

The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06).

A 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.

Written by: Munro NP, Sundaram SK, Weston PM, Fairley L, Harrison SC, Forman D, Chahal R.

Reference:  Int J Radiat Oncol Biol Phys. 2009 Aug 6. doi:10.1016/j.ijrobp.2009.04.050

PubMed Abstract  PMID:19665319

See also: http://www.springerlink.com/content/ax07pj2lfgphqk50/

Conclusion: Our results indicate that a smaller dose of anticancer drugs should be infused from the bilateral internal iliac arteries for safer pelvic BOAI.

http://www.ncbi.nlm.nih.gov/pubmed/2471758

These results demonstrate that BOAI therapy is effective for the treatment of progressive cervical carcinoma by increasing intratumoral concentrations of the drugs.

http://www.biomedexperts.com/Abstract.bme/9313660/Balloon-occluded_arterial_infusion_as_a_useful_neoadjuvant_chemotherapy_for_bladder_cancer

CONCLUSION: In patients diagnosed as stage T2 and T3a, or stage T1 with multiple large tumours difficult to be treat by transurethral resection, BOAI should be considered as the first choice to decrease the stage or to confirm the pathological staging.

Radiochemotherapy for bladder cancer[xxvi]

Wednesday, 22 July 2009

Department of Radiation Oncology, University Hospitals, Erlangen, Germany.

Standard treatment for muscle-invasive bladder cancer is cystectomy. Multimodality treatment, including transurethral resection of the bladder tumour, radiation therapy, chemotherapy and deep regional hyperthermia, has been shown to produce survival rates comparable with those of cystectomy. With these programmes, cystectomy has been reserved for patients with incomplete response or local relapse. During the past two decades, organ preservation by multimodality treatment has been investigated in prospective series from single centres and co-operative groups, with more than 1000 patients included. Five-year overall survival rates in the range of 50-60% have been reported, and about three-quarters of the surviving patients maintained their bladder.

Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumour size (< 5cm), early tumour stage, a visibly and microscopically complete transurethral resection, absence of ureteral obstruction, and no evidence of pelvic lymph node metastases. On multivariate analysis, the completeness of transurethral resection of a bladder tumour was found to be one of the strongest prognostic factors for overall survival. Patients at greater risk of new tumour development after initial complete response are those with multifocal disease and extensive associated carcinoma in situ at presentation. Close co-ordination among all disciplines is required to achieve optimal results. Future investigations will focus on optimising radiation techniques, including all possibilities of radiosensitisation (e.g. concurrent radiochemotherapy, deep regional hyperthermia), and incorporating more effective systemic chemotherapy, and the proper selection of patients based on predictive molecular makers.

Written by: Ott OJ, Rödel C, Weiss C, Wittlinger M, Krause FS, Dunst J, Fietkau R, Sauer R.

Reference: Clin Oncol (R Coll Radiol). 2009 Jun 27. doi:10.1016/j.clon.2009.05.005

PubMed Abstract PMID:19564101

Safety of active surveillance program for recurrent nonmuscle-invasive bladder carcinoma[xxvii]

Urology, 07/07/09

In a study to explore the experience with a group of pts with low-risk tumors included in an observation and monitoring program after diagnosis of recurrence, it was found that pts with recurrent, small (<1 cm), nonmuscle-invasive bladder tumors can be safely offered monitoring under an active surveillance protocol, with minimal risk of progression in either grade or stage, thus reducing the amount of surgical intervention pts might undergo.

Methods

  • A prospective cohort study was done in pts diagnosed with recurrent, nonmuscle-invasive bladder cancer maintained under an active surveillance protocol.
  • Inclusion criteria were papillary tumors with negative cytology findings, previous nonmuscle-invasive tumor (Stage pTa, pT1a), grade 1-2, size <1 cm, and number of tumors <5.
  • No symptomatic pts or those with carcinoma in situ or grade 3 tumors were included.
  • A retrospective analysis of a control group of pts with clinical characteristics similar to those of pts on active surveillance, but who underwent transurethral resection immediately after recurrence was diagnosed was also performed.

Results

  • Data from 64 pts (70 observation events) were analyzed.
  • Mean pt age was 66.7 yrs.
  • Median follow-up was 38.6 mos.
  • Median time pts remained in observation was 10.3 mos.
  • Tumor histologic features before observation were Stage pTa in 77.1%, Stage pT1a in 22.9%, grade 1 in 67.1%, and grade 2 in 23%.
  • After 10.3 mos, 93.5% of pts had not progressed in stage and 83.8% had not progressed in grade.
  • None of the pts experienced progression to muscle-invasive disease.
  • Comparison between rates of progression and control groups showed no statistically significant difference.

What happens to the patients with muscle-invasive bladder cancer who refuse cystectomy after neoadjuvant chemotherapy?[xxviii]

Ruchir Maheshwari, Aneesh Srivastava
Department of Urology and Renal Transplantation, SGPGIMS, Raibareilly Road, Lucknow-226 014, India

Date of Web Publication24-Jun-2009

Summary

This is a prospective study carried out to determine the outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. Sixty-three patients were evaluated between 1995 and 2001 who declined to undergo a planned cystectomy because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy. Herr assessed patient, tumor and treatment features for a median follow- up of 86 months, all patients being followed-up for more than 5 years. Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with the overall survival. The most significant treatment variable predicting better survival was complete resection of the invasive tumor on restaging transurethral resection (TUR) before starting chemotherapy. Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of the surviving patients had solitary, small and low-stage invasive tumors completely resected and 83% survived without relapses in the bladder. [1]

Comments

Radical cystectomy and pelvic lymph node dissection is an excellent treatment for organ-confined disease. Many patients with extravesical or lymph node-positive bladder cancer will develop recurrent disease, often with distant metastases, and will ultimately die of their disease. Given the lethality of muscle-invasive bladder cancer, there is a definite need for effective systemic chemotherapy. Neoadjuvant chemotherapy has been extensively investigated in muscle-invasive bladder cancer. When taken together, the randomized controlled trials of neoadjuvant cisplatin-based combination chemotherapy demonstrate an improved survival over cystectomy alone. In addition, neoadjuvant chemotherapy can result in downstaging of primary tumors. [2]

The Advanced Bladder Cancer Metaanalysis Collaboration concluded that platinum-based combination neoadjuvant chemotherapy and cystectomy continues to show a clear and modest benefit for survival and disease-free survival of patients with muscle-invasive bladder cancer over radical surgery alone. [3] Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive, extravesical (T > 3a) disease at presentation. Chemotherapy aims to treat undetected metastasis and radical cystectomy provides the best control of the primary tumor. Most survivors achieve major response to chemotherapy and have an increased likelihood of having no residual tumor (pT0) in the cystectomy specimen. [4] The author has analyzed whether patients who have pathological pT0 tumors after chemotherapy would have survived without subsequent cystectomy.

In the present study, 64% of the patients survived, with 54% of them having an intact functional bladder (35% of total cohort). Relapse occurred in the majority of the patients (64%), resulting in an additional disease-related mortality of 30%. The patients most likely to relapse had multiple or large tumors that were not clinically confined to the bladder. Delayed cystectomy salvaged fewer than half of the patients relapsing with persistent or new invasive bladder cancers.

Few other studies have dealt on conservative, bladder- sparing management of muscle-invasive transitional cell carcinoma (TCC) bladder using multimodality treatment. [5] These authors have used chemoradiotherapy for tumor control. Perdonà et al., have reported 121 patients with T2, T3 or T4 bladder cancer who underwent induction by TUR of the tumor and received two cycles of neoadjuvant chemotherapy followed by radiotherapy (RT) or radiochemotherapy (RCT). Six weeks after RT or RCT, responses were evaluated by restaging TUR. Patients who achieved a complete response were observed at regular intervals. In patients who had persistent or recurrent invasive tumor, further treatment was recommended. Treatment modality, tumor classification and resection status after initial TUR had an impact on survival rates (P = 0.04, 0.02 and 0.02, respectively).

These studies highlight the fact that patients refusing cystectomy after chemotherapy are at high risk for disease-related mortality. At the same time, patients with small, clinically confined single tumors, which can be visibly and microscopically completely resected before neoadjuvant chemotherapy, are most likely to survive without cystectomy. They need a close follow-up as they remain at risk for new tumors in the bladder.

References

1.Herr HW. Outcome of Patients Who Refuse Cystectomy after Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer. Eur Urol 2008;54:126-32.

2.Vaughn DJ, Malkowicz SB. Neoadjuvant Chemotherapy in Patients with Invasive Bladder Cancer. Urol Clin N Am 2005;32:231-7.

3.Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systemic review and meta-analysis of individual patient data. Eur Urol 2005;48:202-6.

4.Schultz PK, Herr HW, Zhang ZF, Bajorin DF, Seidman A, Sarkis A, et al . Neoadjuvant chemotherapy for invasive bladder cancer: Prognostic factors for survival of patients treated with M-VAC with 5-year follow- up. J Clin Oncol 1994;12:1394-401.

5.Perdonà S, Autorino R, Damiano R, De Sio M, Morrica B, Gallo L, et al . Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: A multi-institutional, long-term experience. Cancer 2008;112:75-83.

Radical Cystectomy versus Radical Radiotherapy[xxix]


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


[xiv] Almudena Zapatero M.D., Ph.D.a, Carmen Martin de Vidales M.D., Ph.D.a, Ramón Arellano M.D.b, Gloria Bocardo M.D.b, Mar Pérez M.D.c and Patricia Ríos M.D.a (aDepartment of Radiation Oncology, Hospital Universitario de la Princesa, Madrid, Spain; bDepartment of Urology, Hospital Universitario de la Princesa, Madrid, Spain; cDepartment of Medical Oncology, Hospital Universitario de la Princesa, Madrid, Spain)

[xxix] Eur Urol. 2003 Mar;43(3):246-57.

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One Response to “Ian Clements: ‘radical cystectomy alternatives’ research – for bladder cancer”

  1. overactive bladder treatment…

    Ian Clements: ‘radical cystectomy alternatives’ research – for bladder cancer « Cancerfighter’s Weblog…

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