Radiation Therapy or Surgery in Treating Patients Receiving Chemotherapy for Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      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: 
      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.
    

Intervention name(s): therapeutic conventional surgery; radiation therapy
Intervention type(s): Procedure; Radiation
Intervention description(s): Patients undergo radical cystectomy; Patients undergo radiotherapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: transitional cell carcinoma of the bladder; stage II bladder cancer; stage III bladder cancer