Andrea Necchi1, Luigi Mariani2, Salvatore Lo Vullo2, Evan Y Yu3, Michael E Woods4, Yu-Ning Wong5, Lauren C Harshman6, Ajjaj Alva7, Cora N Sternberg8, Aristotelis Bamias9, Petros Grivas10, Vadim S Koshkin10, Florian Roghmann11, Jakub Dobruch12, Bernie J Eigl13, Lucia Nappi13, Matthew I Milowsky4, Guenter Niegisch14, Sumanta K Pal15, Ugo De Giorgi16, Federica Recine16, Ulka Vaishampayan17, Dominik D Berthold18, Daniel W Bowles19, Jack Baniel20, Christine Theodore21, Sylvain Ladoire22, Sandy Srinivas23, Neeraj Agarwal24, Simon Crabb25, Srikala Sridhar26, Ali-Reza Golshayan27, Carsten Ohlmann28, Evanguelos Xylinas29, Thomas Powles30, Johnathan E Rosenberg31, Joaquim Bellmunt6, Bas van Rhijn32, Matthew D Galsky33, Kees Hendricksen32. 1. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it. 2. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 3. University of Washington, Seattle, WA, USA. 4. University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, NC, USA. 5. Fox Chase Cancer Center, Philadelphia, PA, USA. 6. Dana-Farber Cancer Institute, Boston, MA, USA. 7. University of Michigan, Ann Arbor, MI, USA. 8. San Camillo Forlanini Hospital, Rome, Italy. 9. University of Athens, Athens, Greece. 10. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. 11. Ruhr-University Bochum, Marien Hospital Herne, Herne, Germany. 12. Centre of Postgraduate Medical Education, European Health Centre Otwock, Poland. 13. British Columbia Cancer Agency, Vancouver, BC, Canada. 14. Heinrich-Heine-University, Medical faculty, Department of Urology, Düsseldorf, Germany. 15. City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 16. IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Meldola, Italy. 17. Karmanos Cancer Institute, Detroit, MI, USA. 18. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 19. Denver Veterans Affairs Medical Center, Eastern Colorado Health Care System, Denver, CO, USA. 20. Rabin Medical Center, Petach Tikva, Israel. 21. Hospital Foch, Suresnes, France. 22. Center Georges-François Leclerc, Dijon, France. 23. Stanford University School of Medicine, Stanford, CA, USA. 24. University of Utah, Salt Lake City, UT, USA. 25. University of Southampton, Southampton, United Kingdom. 26. Princess Margaret Hospital, University Health Network, Toronto, Canada. 27. Medical University of South Carolina, Charleston, SC, USA. 28. Saarland University, Homburg, Germany. 29. Cochin Hospital, Assistance-Publique Hôpitaux de Paris, Paris Descartes University, Paris, France. 30. Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, UK. 31. Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 32. The Netherlands Cancer Institute, Amsterdam, The Netherlands. 33. Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY, USA.
Abstract
BACKGROUND: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. OBJECTIVE: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic±RP) only, first-line platinum-based chemotherapy given. INTERVENTION: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. RESULTS AND LIMITATIONS: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p=0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p=0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. CONCLUSIONS: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. PATIENT SUMMARY: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies.
BACKGROUND: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. OBJECTIVE: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic±RP) only, first-line platinum-based chemotherapy given. INTERVENTION: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. RESULTS AND LIMITATIONS: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p=0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p=0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. CONCLUSIONS: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. PATIENT SUMMARY: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies.
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