RATIONALE: Lymphadenectomy may remove tumor cells that have spread to nearby lymph nodes in patients with invasive bladder cancer. It is not yet known whether extended pelvic lymphadenectomy is more effective than standard pelvic lymphadenectomy during surgery. PURPOSE: This randomized phase II trial is studying standard pelvic lymphadenectomy to see how well it works compared to 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Patients undergo radical cystectomy
Patients undergo standard pelvic lymphadenectomy.
Patients undergo extended pelvic lymphadenectomy
5-year Disease-free Survival (DFS)
Comparing 5-year disease-free survival (DFS) in participants undergoing radical cystectomy for muscle-invasive urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and extended pelvic lymph node dissection (PLND) compared to radical cystectomy and standard pelvic lymphadenectomy. Disease-free survival is defined as the time from the date of randomization to date of first documentation of relapse/recurrence or death due to any cause. Participants last known to be alive without report of relapse/recurrence are censored at date of last contact. Criteria for recurrence included measurable disease on cross-sectional imaging or plain radiography targeting lung, liver, and bone. If local pelvic recurrence was identified on digital rectal examination, biopsy was required for confirmation. Second primary tumors of the upper urinary tract or retained urethra were not considered to be recurrence.
Time frame: Duration of treatment and follow-up until death or 6 years after randomization
5-year Overall Survival (OS)
Comparing 5-year overall survival (OS) in participants randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy. Overall survival is defined as the time from date of randomization to date of death from any cause. Participants known to be alive are censored at date of last contact.
Time frame: Duration of treatment and follow-up until death or 6 years after randomization
Median Operative Time
Evaluating duration of surgery in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: Duration of surgery
Median Days in Hospital
Evaluating duration of post-operative hospital stay in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: From date of operation to 90 days post-operation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Masking
NONE
Enrollment
658
Los Angeles County-USC Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCSF Medical Center-Mount Zion
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
...and 25 more locations
Use of Nerve Preservation
Evaluating the frequency of nerve sparing surgery in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: Duration of surgery
Lymph Node Counts
Evaluating the number of positive lymph nodes removed during surgery as well as the total number of lymph nodes removed in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: Duration of surgery
Receipt of Adjuvant Chemotherapy
Evaluating the receipt of adjuvant chemotherapy in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy. Participants that reported plans to start adjuvant chemotherapy are included in these counts.
Time frame: From date of operation to 90 days post-operation
Frequency of Post-Operative Local Recurrence
Evaluating the frequency of post-operative local and retroperitoneal soft-tissue recurrence in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: From date of operation to 90 days post-operation
Post-Operative Morbidity
Evaluating perioperative morbidity (death within 30 days of surgery) and post-operative morbidity (death within 90 days of surgery) in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Time frame: From date of operation to 90 days post-operation