Radical Cystectomy versus Trimodality Therapy for Muscle-Invasive Urothelial Carcinoma of the Bladder
Kenneth A. Softness, MD1, Sumedh Kaul, MS1, Aaron Fleishman, MPH1, Jason A. Efstathiou, MD, PhD2, Joaquim Bellmunt, MD, PhD1, Simon P. Kim, MD3, Ruslan Korets, MD1, Peter F. Chang, MD, MPH1, Andrew A. Wagner, MD1, Aria F. Olumi, MD1, Boris Gershman, MD1.
1Beth Israel Deaconess Medical Center, Boston, MA, USA, 2Massachusetts General Hospital, Boston, MA, USA, 3University of Colorado, Aurora, CO, USA.
Introduction and Objective: The comparative effectiveness of radical cystectomy (RC) and trimodality therapy (TMT) for muscle-invasive bladder cancer remains uncertain, as no randomized data exist. A phase 3 trial (SPARE) was attempted in the UK, but randomization was deemed infeasible and the trial was closed. Herein, we emulated the SPARE trial to evaluate the comparative effectiveness of RC versus TMT.
Methods: We used the NCDB to emulate a target trial designed to resemble the SPARE trial. We identified patients aged 40-79 with cT2-3 cN0 cM0 urothelial carcinoma of the bladder diagnosed from 2006-2015 who were treated with multiagent neoadjuvant chemotherapy + RC with lymphadenectomy (RC arm) or multiagent chemotherapy + 3D conformal radiotherapy to the bladder (>64 Gy; or >55 Gy in >2.5 Gy/fraction; or 39-45 Gy with salvage RC; TMT arm). We fit a flexible logistic regression model for treatment to estimate the propensity score, and then used inverse probability of treatment weights (IPWs) to evaluate the associations of treatment group with overall survival (OS).
Results: A total of 2,048 patients were included, of whom 1,812 underwent RC and 236 underwent TMT. After IPW-adjustment, baseline characteristics were balanced. Median follow-up was 29.0 months, during which time 838 deaths occurred. The 5-year IPW-adjusted OS was 53% for RC and 44% for TMT (p=0.42; Figure 1). Compared to RC, TMT was not associated with a statistically significant difference in OS (HR 0.97; 95% CI 0.64-1.19; p=0.40). When examining heterogeneity of treatment effects according to cT stage, age, and Charlson score, RC appeared to be associated with improved OS only for patients with cT3 disease (HR 0.42, p=0.01; Figure 2). Similar results were observed in sensitivity analyses.
Conclusions: In observational analyses designed to emulate the SPARE trial, there was no statistically significant difference in OS between RC and TMT. Heterogeneity of treatment effects suggested improved survival with RC only for cT3 disease.
Funding: None
Figure 1: IPW-adjusted Kaplan-Meier plot of overall survival for radical cystectomy (RC) versus trimodality therapy (TMT).
Figure 2: Heterogeneity of treatment effects according to cT stage, age, and Charlson score. 
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