Clinical Predictors and Prognostic Significance of Pathologic Disease Upstaging at Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer

Abstract

Introduction: Staging inaccuracies in muscle-invasive bladder cancer (MIBC) can lead to undertreatment or overtreatment. We evaluated clinical and pathological predictors of pathologic upstaging (pUS) stratifying by neoadjuvant chemotherapy (NAC) receipt among patients undergoing robot-assisted radical cystectomy (RARC). Methods: We included patients with MIBC (≥cT2N0M0) who underwent RARC from February 2004 through October 2020. Patients were grouped as (1) pUS with NAC, (2) pUS without NAC, and (3) no pUS (reference). Baseline characteristics were summarized using descriptive statistics. Logistic regression assessed the association between baseline characteristics and odds for upstaging. Kaplan–Meier method estimated overall survival (OS) and recurrence-free survival (RFS), and log-rank test compared the survival distribution between groups. Univariable and multivariable Cox regression models identified variables associated with OS and RFS. Results: Among 277 patients, 38.6% (n = 107) were upstaged with NAC (n = 37) or without NAC (n = 70). Most were male (79%), white (72%), and had cT2 stage (85%). Median age at surgery was 72 yrs. Preoperative hydronephrosis showed higher odds of upstaging [OR 2.24 (95% CI, 1.31–3.81), p = 0.003]. pUS with NAC [HR 1.99 (95% CI, 1.23–3.22), p = 0.005] and without NAC [HR 3.18 (95% CI, 2.21–4.55), p < 0.001] predicted worse OS (33.5 vs. 18.8 mos) compared to patients without pUS (135.3 mos). pUS with NAC [HR 2.49 (95% CI, 1.58–3.94) p < 0.001] and without NAC [HR 3.02 (95% CI 2.11–4.31), p < 0.001] predicted worse RFS. Conclusions: Preoperative hydronephrosis was the strongest predictor for pUS, independent of other baseline covariates. This highlights the need for better pre-operative risk stratification strategies for patients with MIBC undergoing RARC.