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 Mir; Bas W G van Rhijn

doi:10.1007/s00345-021-03776-5

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

World J Urol. 2021 Dec;39(12):4363-4371. doi: 10.1007/s00345-021-03776-5. Epub 2021 Jul 1.

Authors

Francesco Claps^#^{1

2}, Maaike W van de Kamp^#¹, Roman Mayr^#³, Peter J Bostrom^{4

5}, Joost L Boormans⁶, Markus Eckstein⁷, Laura S Mertens¹, Egbert R Boevé⁸, Yann Neuzillet^{1

9}, Maximilian Burger³, Damien Pouessel^{9

10}, Carlo Trombetta², Bernd Wullich¹¹, Theo H van der Kwast¹², Arndt Hartmann⁷, Yves Allory^{9

13}, Yair Lotan¹⁴, Shahrokh F Shariat^{14

15

16

17

18}, Tahlita C M Zuiverloon⁶, M Carmen Mir¹⁹, Bas W G van Rhijn^{20

21

22}

Affiliations

¹ Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
² Department of Medicine, Surgery and Health Sciences, Urological Clinic, University of Trieste, Trieste, Italy.
³ Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany.
⁴ Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada.
⁵ Department of Urology, Turku University Hospital and University of Turku, Turku, Finland.
⁶ Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
⁷ Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany.
⁸ Department of Urology, St Franciscus Hospital, Rotterdam, The Netherlands.
⁹ Institut Curie, CNRS, UMR144, Molecular Oncology Team, PSL Research University, 75005, Paris, France.
¹⁰ Department of Medical Oncology, Claudius Regaud Institute, Toulouse University Cancer Center (IUCT) Oncopole, 31000, Toulouse, France.
¹¹ Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany.
¹² Department of Pathology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada.
¹³ Department of Pathology, Institut Curie, 75005, Paris, France.
¹⁴ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁶ Department of Urology, Weill Cornell Medical College, New York, NY, USA.
¹⁷ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁸ Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
¹⁹ Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain.
²⁰ Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. [email protected].
²¹ Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany. [email protected].
²² Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada. [email protected].

^# Contributed equally.

PMID: 34196758
DOI: 10.1007/s00345-021-03776-5

Abstract

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.

Keywords: Bladder; Cancer; Cystectomy; Margin; Soft tissue; Ureter; Urethra; Urothelial carcinoma.

Publication types

Multicenter Study

MeSH terms

Aged
Cohort Studies
Cystectomy* / methods
Female
Humans
Male
Margins of Excision*
Middle Aged
Risk Factors
Survival Rate
Urinary Bladder Neoplasms / mortality*
Urinary Bladder Neoplasms / pathology
Urinary Bladder Neoplasms / surgery*