Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder

•Utilized strict criteria to emulate pragmatic target trial.•Compared cystectomy with trimodality therapy for muscle invasive bladder cancer.•Radical cystectomy had similar overall survival to trimodality therapy.•Radical cystectomy has improved survival in clinical T3 disease. 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, however, was deemed infeasible and closed. To emulate the SPARE trial using observational data. We identified patients aged 40 to 79 with cT2-3cN0cM0 urothelial carcinoma of the bladder diagnosed from 2006 to 2015 who were treated with multiagent neoadjuvant chemotherapy + RC with lymphadenectomy (RC arm) or multiagent chemotherapy + 3D conformal radiotherapy to the bladder (TMT arm) in the National Cancer Database. The primary outcome was overall survival (OS). We fit a flexible logistic regression model for treatment to estimate the propensity score, and then used inverse probability of treatment weights to evaluate the associations of treatment group with OS. A total of 2,048 patients were included, of whom 1,812 underwent RC and 236 underwent TMT. Median follow-up was 29.0 months. After propensity score adjustment, compared to TMT, RC was not associated with a statistically significant difference in OS (HR 0.87; 95% CI 0.64–1.19; P = 0.40). When examining heterogeneity of treatment effects, RC appeared to be associated with improved OS only for patients with cT3 disease. Similar results were observed in sensitivity analyses. Our study is limited by the retrospective design and the lack of cancer-specific survival data. 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.