S1011 Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer

OBJECTIVES:

Primary

• To compare disease-free survival (DFS) of patients with muscle-invasive urothelial carcinoma of the bladder undergoing radical cystectomy with extended pelvic lymph node dissection (PLND) or standard pelvic lymphadenectomy.

Secondary

• To compare overall survival (OS) of patients randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy.
• To evaluate operative time; whether or not nerve sparing was performed, intraoperative, peri-operative and 90-day morbidity and mortality; length of hospital stay; histology (pure urothelial versus mixed); lymph node counts and lymph node density; adjuvant chemotherapy received; and local and retroperitoneal soft tissue recurrence in patients randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy.
• To collect peripheral blood and two paraffin-embedded blocks of the primary tumor for translational medicine studies, including circulating tumor cells (CTCs) and markers of epithelial and mesenchymal transition, and correlate these findings with pathologic T stage and node metastasis as well as DFS and OS.

OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant therapy (yes vs no), clinical stage (T2 vs T3 vs T4a), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radical cystectomy and standard pelvic lymphadenectomy.
• Arm II: Patients undergo radical cystectomy and extended pelvic lymphadenectomy.

Blood and tumor specimens may be collected periodically for translational studies.

After completion of study therapy, patients are followed up periodically for 6 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed urothelial carcinoma of the bladder

• Stage T2, T3, or T4a disease

• No clinical stage consistent with a low-risk of node metastasis (CIS only, T1)
• No T4b disease (fixed lesion)
• Disease that requires primary radical cystectomy and lymph node dissection for definitive treatment

• No laparoscopic surgery
• Predominant urothelial carcinoma with any of the following elements allowed:

• Adenocarcinoma
• Squamous cell carcinoma
• Micropapillary or minor components of other rare phenotype
• No pure squamous cell carcinoma or adenocarcinoma
• No visceral or nodal metastatic disease proximal to the common iliac bifurcation by 2-view chest x-ray and abdominal-pelvic imaging by computerized tomography or MRI of the abdomen and pelvis
• No intra-operative pelvic lymph node involvement (confirmed by frozen section) at or above the bifurcation of the common iliac vessels in any of the extended template

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• ALT and AST ≤ upper limit of normal (ULN)*
• Alkaline phosphatase ≤ ULN*
• Not pregnant or nursing
• Fertile patients must use an effective contraception
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or stage I or II cancer from which the patient is in complete remission for the past 5 years
• Medically suitable to undergo cystectomy, in the physician's opinion NOTE: *Levels may be ≥ ULN provided metastatic disease is excluded using dedicated liver imaging, bone scan, or biopsy.

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior partial cystectomy for invasive bladder cancer
• No prior pelvic surgery that would obviate a complete extended lymphadenectomy (e.g., aorto-femoral/iliac bypass)
• Prior neoadjuvant chemotherapy for this cancer allowed provided it has been completed and patient has recovered
• No prior pelvic irradiation