Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC.
A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers. Patients receiving perioperative radiotherapy were excluded from the study. Kaplan-Meier curves were used to estimate patient survival. Cox regression analysis was used to identify predictors of survival.
Median age at surgery was 70 years (IQR 62-76) with 129 (33%) and 204 (52%) patients had pT3 and pT4 tumors, respectively. Nodal metastasis (pN+) was identified in 148 (38%). Soft tissue PSMs were found in 283 (72%) patients, urethral PSMs in 65 (16.5%), and ureteral PSMs were found in 73 (18.5%). The median follow-up time was 44 months (95% CI 32-60). Median LRFS, MRFS, RFS, CSS, and OS were 14 (95% CI 11-17), 12 (95% CI 10-16), 10 (95% CI 8-12), 23 (95% CI 18-33), and 16 months (95% CI 12-19), respectively. On multivariable Cox regression analysis, the pT3-4 stage, pN+ stage, and multifocal PSMs were independent predictors of LRFS, MRFS, RFS, and OS. Adjuvant chemotherapy improved all oncological outcomes studied (p < 0.05). The number of lymph nodes removed was independently associated with better LRFS, MRFS, and RFS. Advanced age at diagnosis was independently associated with worse OS.
Patients with PSMs following RC have poor outcomes since half of them will recur within a year and will die of their disease. Among all PSMs types, patients with multifocal PSMs harbor the worst prognosis. We observed a benefit of adjuvant chemotherapy, but clinical trials evaluating innovative adjuvant strategies for these patients remain an unmet need.
Cancers. 2022 Nov 22*** epublish ***
Gautier Marcq, Luca Afferi, Yann Neuzillet, Timo Nykopp, Charlotte S Voskuilen, Marc A Furrer, Wassim Kassouf, Atiqullah Aziz, Anne Sophie Bajeot, Mario Alvarez-Maestro, Peter Black, Morgan Roupret, Aidan P Noon, Roland Seiler, Kees Hendricksen, Mathieu Roumiguie, Karl H Pang, Paul Laine-Caroff, Evanguelos Xylinas, Guillaume Ploussard, Marco Moschini, Paul Sargos, YAU Urothelial Group
Division of Urology, McGill University Health Centre, McGill University, 1001 Decarie Blvd, D02.7210, Montreal, QC H4A 3J1, Canada., Department of Urology, Luzerner Kantonsspital, 6000 Luzern, Switzerland., Department of Urology, Foch Hospital, Paris-Saclay-UVSQ University, 92150 Suresnes, France., Department of Surgery, Kuopio University Hospital and University of Eastern Finland, PL 100, 70029 Kuopio, Finland., The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Urology, 1066 CX Amsterdam, The Netherlands., Department of Urology, University Hospital of Bern, University of Bern, 3012 Bern, Switzerland., Department of Urology, München Klinik Bogenhausen, 81925 Munich, Germany., Department of Urology, ICUT CHU, 31300 Toulouse, France., Department of Urology, Hospital Universitario La Paz, 28046 Madrid, Spain., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada., Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 Paris, France., The Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK., Department of BioMedical Research, University of Bern, 3012 Bern, Switzerland., Department of Oncology and Metabolism, Academic Urology Unit, University of Sheffield, Sheffield S10 2TN, UK., Department of Urology, Bichat-Claude Bernard Hospital, Assistance Publique-Hopitaux de Paris, Paris University, 75018 Paris, France., Department of Urology, La Croix du Sud Hospital, 31130 Quint Fonsegrives, France., Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy., Department of Radiotherapy, Institut Bergonie, 33076 Bordeaux, France.