Oncological outcomes after non-surgical management versus radical cystectomy in non-organ-confined non-urothelial bladder cancer

Introduction: We hypothesized that among non-organ-confined (NOC, T3-4 and/or N1-3) non-urothelial carcinoma of urinary bladder (non-UCUB) patients, bladder-sparing non-surgical management (NSM) provides cancer-specific mortality (CSM) rates comparable to those of radical cystectomy (RC). Methods: Within the SEER database (2004–2021) rates of NSM vs. RC use in NOC non-UCUB patients were tabulated. Nearest-neighbor 1:1 propensity score matching (PSM) for age, sex, stage, race/ethnicity, and histological subtype was applied. Cumulative incidence plots depicted five-year CSM. Univariable and multivariable competing risks regression (CRR) models were fitted. Sensitivity analyses were performed within squamous cell carcinoma (SCC), small cell carcinoma (small-CC) and adenocarcinoma (ADK). Results: Of 775 NOC non-UCUB patients, 290 (37.4%) received NSM vs. 485 (62.6%) RC. After PSM, five-year CSM rate was 70.4% after NSM vs. 60.6% after RC and NSM was associated with 1.6-fold higher CSM relative to RC (multivariable HR [mHR]: 1.61, p < 0.001). In sensitivity analyses within 253 (32.6%) SCC, after re-applying PSM, five-year CSM rate was 85.0% after NSM vs. 53.3% after RC and NSM was associated with 2.8-fold higher CSM relative to RC (mHR: 2.80, p < 0.001). Conversely, within 216 (27.9%) small-CC and 135 (17.4%) ADK patients, CSM after NSM did not differ from CSM after RC (54.3 vs. 62.5%, mHR: 0.85; 69.8 vs. 71.7%, mHR: 1.0; all p > 0.05). Conclusion: In NOC non-UCUB patients, NSM is associated with higher CSM than RC. Subgroup analyses according to histological subtypes suggest that these differences virtually exclusively originated from SCC patients but not from their small-CC and ADK counterparts.