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

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.

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