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