Risk factors associated with positive surgical margins’ location at radical cystectomy and their impact on bladder cancer survival

Francesco Claps, Maaike W. van de Kamp, Roman Mayr, Peter J. Bostrom, Joost L. Boormans, Markus Eckstein, Laura S. Mertens, Egbert R. Boevé, Yann Neuzillet, Maximilian Burger, Damien Pouessel, Carlo Trombetta, Bernd Wullich, Theo H. van der Kwast, Arndt Hartmann, Yves Allory, Yair Lotan, Shahrokh F. Shariat, Tahlita C.M. Zuiverloon, M. Carmen MirBas W.G. van Rhijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Purpose: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). Methods: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan–Meier method was used to estimate DSS stratified by margins’ status and location. Log-rank statistics and Cox’ regression models were used to determine significance. Results: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). Conclusions: PSMs’ location represents distinct risk factors’ patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.

Original languageEnglish
Pages (from-to)4363-4371
Number of pages9
JournalWorld Journal of Urology
Issue number12
Early online date1 Jul 2021
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
The authors would specifically like to acknowledge the Dutch urology departments of Reinier de Graaf Gasthuis (Delft), Franciscus Gasthuis and Vlietland (Rotterdam), Haga (The Hague) and Amphia (Breda) hospitals for their contribution to the Rotterdam cohort. The authors would like to acknowledge the International Bladder Cancer Network (IBCN) and the Bladder Cancer Advocacy Network (BCAN) for providing the platform to collaborate on this project. FC and YN were supported by the European Urological Scholarship Programme (EUSP). Amsterdam: The Institutional Review Board of the Netherlands Cancer Institute?Antoni van Leeuwenhoek hospital (CFMPB-160 and IRBd18126). Rotterdam: The medical-ethical board of Erasmus MC, Rotterdam (MEC 168.922/1998/55). Regensburg: Medical ethical board of the University of Regensburg (16-101-0218). Paris: The regional ethics board of Ile-de-France IX?Comit? de protection des personnes?Ile-de-France IX?Cr?teil (11-052). Toronto: The regional ethics board of the University Health Network, Toronto (02-0515-C, 08-0263-T, 09-0826-CE and 09-0556-TE). Turku: Ethical committee of the hospital district of South-West Finland, No: ETMK 6/2006. Erlangen: The ethical and translational boards, Erlangen (217_18 Bc and 329_16-B). Dallas: The Institutional Review Board for the Protection of Human Subjects at University of Texas Southwestern Medical School: STU 102014-008.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.


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