3246 - A Single Institution Experience Comparing Outcomes of Muscle Invasive Bladder Cancer of Urothelial or Alternative Histology Treated with Trimodality Therapy

Purpose/Objective(s): Data on bladder-preserving therapy for muscle-invasive bladder cancer (MIBC) with variant histology are limited. We analyzed outcomes for urothelial (UC) vs alternative histology (i.e., other than UC-only) MIBC treated with trimodality therapy (TMT).

Materials/Methods: We retrospectively analyzed MIBC patients treated with TMT at our institution (1998–2025) for clinicopathologic features, treatment, and outcomes. Pathology records were reviewed for WHO (2022)-defined subtypes or UC with divergent differentiation (UCDD). ?² test was used to compare categorical variables. Overall survival (OS) from radiation (RT) and bladder-intact event-free survival (BI-EFS) were estimated by KM method and groups compared by log-rank test. Cox regression was used for continuous variables and to assess predictors in multivariable analyses (MVA).

Results: We identified 189 patients, median age 73 years (range 40-93), 79.9% male. Most had UC-only histology (61.4%), cT2 (65.1%), unifocal tumors (68%), no hydronephrosis (74.1%) and no in situ disease (CIS) (69.3%). Alternative histology patients (n=73) (38.6%) included: 34 (46.6%) UCDD, 21 (43.8%) specific subtypes, and 7 (9.6%) non-UC. UCDD included squamous (53%), neuroendocrine (23.5%) and glandular (23.5%) differentiation. In tumors of 1 subtype (n=21), micropapillary (28.6%) and nested (19%) were most common. Hypofractionated RT was used in 41.3%, pelvic nodes were treated in 77.8%. Median RT dose was 60 Gy (range 50-74.4) to bladder, 40 Gy to nodes; 96.2% received concurrent chemotherapy. NAC was delivered to 31.2%, of which 44.1% had complete clinical response (cCR). Three-year OS was 68.0% (UC-only 67.6% vs alternative histology 63.4%). Table 1 shows median follow-up (MFU) and defined endpoints for UC-only vs alternative histology. Overall, cCR after NAC and age were associated with BI-EFS (p < 0.05); cCR remained predictive on MVA (HR 0.28, 95CI 0.11-0.72, p=0.008). For OS, hydronephrosis severity (p=0.04), MIBC or distant relapse (p<0.01), and age (p=0.001) were predictive on MVA. Comparing UC-only vs alternative histology showed differences in CIS (p=0.036), receipt of NAC (p=0.001), and RT fractionation (p=0.037). Among UCDD, glandular differentiation had more favorable OS (p=0.014).

Conclusion: TMT for MIBC achieved durable survival and organ preservation in select patients, including those with alternative histology.