Upstaging and Survival Outcomes for Non-Muscle Invasive Bladder Cancer after Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

Introduction: We sought to describe the incidence, risk factors, and survival outcomes associated with pathologic upstaging from non-muscle invasive bladder cancer (NMIBC) to muscle invasive bladder cancer (MIBC) after robot-assisted radical cystectomy (RARC). Methods: We reviewed the International Robotic Cystectomy Consortium database between 2004 and 2020. Upstaging was defined as ≥pT2 or pathologic node positive (pN+) at final pathology analysis from clinical <T2N0M0. Descriptive statistics were used to summarize data. Cochran-Armitage test was used to depict upstaging trend over time. Multivariate regression models were used to depict variables associated with upstaging. Kaplan-Meier curves were used to describe disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS). Results: A total of 463 patients underwent RARC for NMIBC. Upstaging occurred in 145 (31%) patients. Upstaged patients were older (70 vs 67 years, p < 0.01), more likely to have American Society of Anesthesiologists (ASA) score (≥3; 55% vs 44%, p = 0.04), and had higher rate of preoperative hydronephrosis (26% vs 10%, p < 0.01). They were more likely to have positive surgical margins (10% vs 3%, p = 0.01), recurrences (28% vs 9%, p < 0.01), and to receive adjuvant/salvage treatment (26% vs 3%, p < 0.01). On multivariate analysis, upstaging was associated with older age (odds ratio [OR] 1.04; confidence interval [CI] 1.01-1.07, p < 0.01), cT1 vs cTis (OR 4.25; CI 1.57-11.48, p < 0.01), cT1 vs cTa (OR 2.92; CI 1.40-6.06, p < 0.01), and preoperative hydronephrosis (OR 3.18; CI 1.60-6.32, p < 0.01). Upstaged patients had worse 5-year RFS (53% vs 85%, log rank p < 0.01), DSS (66% vs 93%, log rank p < 0.01), and OS (49% vs 74%, log rank p < 0.01). The rate of upstaging did not significantly change over time (38% in 2004 to 27% in 2019, p = 0.17). Conclusion: Upstaging to MIBC occurred in a significant proportion of patients after RARC for NMIBC and was associated with worse survival outcomes. Older patients, those with cT1 disease and hydronephrosis were more likely to upstage.