Radiation Therapy or Surgery in Treating Patients Receiving Chemotherapy for Bladder Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective than surgery in treating patients with bladder cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with surgery in treating patients with bladder cancer who are receiving chemotherapy.

Detailed Description
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OBJECTIVES: Primary To determine the feasibility and patient acceptability of radical cystectomy vs selective bladder preservation (SBP) after neoadjuvant chemotherapy in patients with muscle-invasive transitional cell carcinoma of the bladder. To determine compliance rates of patients with their assigned treatments. To determine if bladder preservation is equivalent to radical cystectomy, in terms of overall survival, in responders to neoadjuvant chemotherapy. Secondary To compare the overall survival of patients receiving SBP vs radical cystectomy. To determine the rate of salvage cystectomy in patients undergoing bladder preservation. To determine and compare the toxicity of treatment in both arms. To determine and compare quality of life of patients treated with these regimens. To compare locoregional progression-free and metastasis-free survival of patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to cancer center and randomized to 1 of 2 treatment arms. Patients are assessed after completion of 3 courses of pre-study neoadjuvant chemotherapy. Patients with poor response (≥ pT2, residual pT2, macroscopic invasive tumor) undergo immediate radical cystectomy (within 6 weeks fo completing chemotherapy). Patients* with responsive disease (≤ pT1 tumor or macroscopically normal bladder) proceed to course 4 of chemotherapy (on-study) followed by treatment according to randomization arm. NOTE: *Patients with a clear bladder or those who are unsure of their histological results prior to course 4 also proceed to chemotherapy. Course 4 of neoadjuvant chemotherapy: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 4 hours on day 1. Arm I (radical cystectomy): Patients undergo a radical cystectomy, including pelvic lymphadenectomy, between 4 and 6 weeks after initiating course 4 of chemotherapy. Arm II (selective bladder preservation): Patients with no visible residual tumor (cT0 or pT0) or residual but superficial tumor (pTa, pT1) undergo radiotherapy beginning within 4-6 weeks of day 1 of course 4 and continuing for 6.5 weeks. Health-related quality of life is assessed periodically. After completion of study treatment, patients are followed periodically for up to 5 years.

Official Title
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Randomised Trial of Selective Bladder Preservation Against Radical Excision (Cystectomy) in Muscle Invasive T2/T3 Transitional Cell Carcinoma of the Bladder - Feasibility Study

Conditions
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Bladder Cancer

Intervention / Treatment
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* Procedure: therapeutic conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma (TCC) of the bladder Clinical stage T2-T3, N0, M0 No widespread carcinoma in situ (CIS) or CIS remote from muscle invasive tumor No adenocarcinoma, squamous cell carcinoma (SCC), small cell carcinoma, or other variant histology N.B. squamoid differentiation or mixed TCC/SCC allowed No simultaneous upper tract, urethral, or prostatic urethral TCC Direct prostatic urethral extension from bladder primary allowed if not involving prostatic stroma Currently receiving 3 courses of gemcitabine hydrochloride-cisplatin or other protocol approved neoadjuvant chemotherapy regimen AND willing and fit to receive a 4th course according to study protocol PATIENT CHARACTERISTICS: WHO performance status 0-1 Hemoglobin > 10 g/dL WBC > 3,000/mm³ Platelet count > 150,000/mm³ Bilirubin < 1.5 times upper limit of normal (ULN) AST < 1.5 times ULN Alkaline phosphatase < 1.5 times ULN Not pregnant Fit for radical cystectomy or radical radiotherapy No prior malignancy within the past 5 years except superficial TCC or CIS No untreated hydronephrosis Patients with hydronephrosis are eligible if the kidney/ureter has been stented or nephrostomy has been inserted and renal function has been maintained No contraindication to radical radiotherapy (e.g., inflammatory bowel disease, radiosensitivity syndrome, or severe diverticular disease) No bilateral total hip replacements No significant comorbid medical conditions that would interfere with administration of any protocol treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior pelvic radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients undergo a radical cystectomy, including pelvic lymphadenectomy, between 4 and 6 weeks after initiating course 4 of chemotherapy. | Procedure: therapeutic conventional surgery<br>* Patients undergo radical cystectomy<br>|
| Experimental: Arm II<br>Patients with no visible residual tumor (cT0 or pT0) or residual but superficial tumor (pTa, pT1) undergo radiotherapy beginning within 4-6 weeks of day 1 of course 4 and continuing for 6.5 weeks. | Radiation: radiation therapy<br>* Patients undergo radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients randomized over 3 years |  |  | 
| Proportion of patients undergoing selective bladder preservation |  |  | 
| Proportion of patients undergoing radical cystectomy |  |  | 
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance with randomized treatment |  |  | 
| Rate of salvage cystectomy after selective bladder preservation |  |  | 
| Toxicity as assessed by NCI CTCAE v3.0 |  |  | 
| Quality of life as assessed by the QLQ-C30 v3.0 questionnaire |  |  | 
| Locoregional progression-free, metastasis-free, and overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transitional cell carcinoma of the bladder, stage II bladder cancer, stage III bladder cancer