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

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.