Clinical trial NCT01224665: S1011 Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer
Official title: A Phase III Surgical Trial to Evaluate the Benefit of a Standard Versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bladder Cancer
Keywords: stage II bladder cancer
stage III bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-10-20
Enrollment: 658
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 5-year Disease-free Survival (DFS)
timeFrame: Duration of treatment and follow-up until death or 6 years after randomization
Secondary outcomes:
measure: 5-year Overall Survival (OS)
timeFrame: Duration of treatment and follow-up until death or 6 years after randomization
measure: Median Operative Time
timeFrame: Duration of surgery
measure: Median Days in Hospital
timeFrame: From date of operation to 90 days post-operation
measure: Use of Nerve Preservation
timeFrame: Duration of surgery
measure: Lymph Node Counts
timeFrame: Duration of surgery
measure: Receipt of Adjuvant Chemotherapy
timeFrame: From date of operation to 90 days post-operation
measure: Frequency of Post-Operative Local Recurrence
timeFrame: From date of operation to 90 days post-operation
measure: Post-Operative Morbidity
timeFrame: From date of operation to 90 days post-operation
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Portland Veterans Administration Medical Center
state: Oregon
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: Baylor Saint Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Affairs Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre/Capital District Health Authority
state: Nova Scotia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre (MUHC)
state: Quebec
Study officials:
affiliation: Baylor College of Medicine
name: Seth P. Lerner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmstrom PU, Choi W, Guo CC, Lotan Y, Kassouf W. Bladder cancer. Lancet. 2016 Dec 3;388(10061):2796-2810. doi: 10.1016/S0140-6736(16)30512-8. Epub 2016 Jun 23.
citation: Froehner M, Novotny V, Heberling U, Rutsch L, Litz RJ, Hubler M, Koch R, Baretton GB, Wirth MP. Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. Eur Urol. 2014 Dec;66(6):987-90. doi: 10.1016/j.eururo.2014.07.046. Epub 2014 Aug 19.