Author(s): Seth P. Lerner, M.D., Catherine Tangen, Dr.P.H., Robert S. Svatek, M.D., Siamak Daneshmand, M.D., Kamal S. Pohar, M.D., Eila Skinner, M.D., Anne Schuckman, M.D., Arthur I. Sagalowsky, M.D., Norm D. Smith, M.D., Ashish M. Kamat, M.D., Wassim Kassouf, M.D., Melissa Plets, M.S., Rick Bangs, M.B.A. https://orcid.org/0000-0002-0706-8775, Theresa M. Koppie, M.D., Ajjai Alva, M.D., Francisco G. La Rosa, M.D., Sumanta K. Pal, M.D., Adam S. Kibel, M.D., Daniel J. Canter, M.D., and Ian M. Thompson, Jr., M.D., for the SWOG S1011 Trial Investigators*
BACKGROUND
Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear.
METHODS
We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs. T3 or T4a), and a Zubrod’s performance-status score (0 or 1 vs. 2; assessed on a 5-point scale, with higher scores indicating greater disability). The primary outcome was disease-free survival. Overall survival and safety were also assessed.
RESULTS
Of 658 patients who were enrolled, 592 eligible patients were randomly assigned to undergo extended lymphadenectomy (292 patients) or standard lymphadenectomy (300). Surgery was performed by 36 surgeons at 27 sites in the United States and Canada. Neoadjuvant chemotherapy had been received by 57% of the patients. At a median follow-up of 6.1 years, recurrence or death had occurred in 130 patients (45%) in the extended-lymphadenectomy group and in 127 (42%) in the standard-lymphadenectomy group, and the estimated 5-year disease-free survival was 56% and 60%, respectively (hazard ratio for recurrence or death, 1.10; 95% confidence interval [CI], 0.86 to 1.40; P=0.45). Overall survival at 5 years was 59% in the extended-lymphadenectomy group and 63% in the standard-lymphadenectomy group (hazard ratio for death, 1.13; 95% CI, 0.88 to 1.45). Adverse events of grade 3 to 5 occurred in 157 patients (54%) in the extended-lymphadenectomy group and in 132 (44%) in the standard-lymphadenectomy group; death within 90 days after surgery occurred in 19 patients (7%) and 7 patients (2%), respectively.
CONCLUSIONS
As compared with standard lymphadenectomy, extended lymphadenectomy did not result in improved disease-free or overall survival among patients with muscle-invasive bladder cancer undergoing radical cystectomy and was associated with higher perioperative morbidity and mortality. (Funded by the National Cancer Institute and the Canadian Cancer Society; SWOG S1011 ClinicalTrials.gov number, NCT01224665.)
Author Affiliations
From Baylor College of Medicine (S.P.L.) and the University of Texas M.D. Anderson Cancer Center (A.M.K.), Houston, the University of Texas Health San Antonio (R.S.S.) and CHRISTUS Santa Rosa Medical Center Hospital (I.M.T.), San Antonio, and the University of Texas Southwestern Medical Center, Dallas (A.I.S.) — all in Texas; Stanford University, Stanford (E.S.), Norris Comprehensive Cancer Center, University of Southern California, Los Angeles (S.D., A.S.), and City of Hope Medical Center, Duarte (S.K.P.) — all in California; SWOG Statistics and Data Management Center and Fred Hutchinson Cancer Center — both in Seattle (C.T., M.P.); the Ohio State University, Columbus (K.S.P.); the University of Chicago, Chicago (N.D.S.); McGill University Health Center, Montreal (W.K.); the Bladder Cancer Advocacy Network, SWOG Advocates, Pittsford, NY (R.B.); Oregon Health and Science University, Portland (T.M.K.); the University of Michigan, Ann Arbor (A.A.); the University of Colorado, Aurora (F.G.L.R.); Brigham and Women’s Hospital, Boston (A.S.K.); Fox Chase Cancer Center, Philadelphia (D.J.C.); and Oschsner Medical Center, Jefferson, LA (D.J.C.).
