BackgroundTrimodality bladder-sparing therapy (TMT) is an acceptable treatment for selected patients with muscle-invasive urothelial cancer. Outcomes of TMT in histologic variants remains largely unknown. ObjectiveTo compare outcomes of pure urothelial carcinoma (PUC) to variant urothelial carcinoma (VUC) after TMT. Design, setting, and participantsRetrospective study of patients treated with TMT at a single cancer center from 1993 until 2013. Outcome measurements and statistical analysisKaplan-Meier survival probabilities, and univariate and multivariable Cox regression analysis. Results and limitationsOf 303 patients treated with TMT, 66 (22%) had VUC. Fifty (76%) had VUC with squamous and/or glandular differentiation and 16 (24%) had other forms. Complete response rate after induction TMT was 83% in PUC and 82% in VUC (p=0.9). The 5-yr and 10-yr disease-specific survival (DSS) was 75% and 67% in PUC versus 64% and 64% in VUC. The 5-yr and 10-yr overall survival (OS) was 61% and 42% in PUC versus 52% and 42% in VUC. On multivariable analysis VUC was not associated with DSS (hazard ratio: 1.3, 95% confidence interval: 0.8–2.2, p=0.3) or OS (hazard ratio: 1.2, 95% confidence interval: 0.8–1.7, p=0.4). Salvage cystectomy rates were similar (log-rank p=0.3). Limitations include retrospective design and restriction to variants of urothelial cancer. ConclusionsVUC responded to TMT, and there was no significant difference in complete response, OS, DSS, or salvage cystectomy rates compared with PUC. The presence of VUC should not exclude patients from TMT. Patient summaryThe response of histologic variants of bladder cancer to bladder-sparing chemoradiation is largely unknown. We compared the outcomes of histologic variants of urothelial cancer to pure urothelial cancer in a large series of patients from a single institution. We found that variant histology does not significantly influence outcomes.