Racial and ethnic disparities in variant histology bladder cancer: Insights from SEER 2000–2021.

651 Background: Variant histology bladder cancer (VHBC) - including squamous, plasmacytoid, neuroendocrine/small cell, sarcomatoid, and signet/adenocarcinoma subtypes - is uncommon but associated with poor outcomes. While survival disparities by race and ethnicity are well documented in urothelial carcinoma, whether these persist within VHBC, independent of subtype, stage, and socioeconomic factors, remains unclear. Methods: Using SEER 18 registries (2000–2021), we identified patients with VHBC and excluded pure urothelial carcinoma (ICD-O-3 code 8120). Histologic subtypes were grouped as squamous, micropapillary, plasmacytoid, neuroendocrine/small cell, sarcomatoid/spindle, and signet/adenocarcinoma. Race/ethnicity was categorized as non-Hispanic (NH) White (reference), NH Black, Hispanic, and NH Asian/Pacific Islander (PI). The primary endpoint was cancer-specific survival (CSS). Multivariable Cox models adjusted for histologic subtype, stage, socioeconomic quartile, rurality, and diagnosis year. Logistic regression evaluated odds of presenting with a high-risk variant (plasmacytoid, neuroendocrine/small cell, sarcomatoid, or signet/adenocarcinoma). Results: We identified 1,353 VHBC cases (NH White 79.9%, NH Black 8.0%, Hispanic 6.1%, NH Asian/PI 6.1%). On multivariable analysis, NH Black patients had worse CSS vs NH White (aHR 1.39, 95% CI 1.10–1.75, p = 0.005). Hispanic (aHR 0.77, 95% CI 0.57–1.05, p = 0.10) and NH Asian/PI (aHR 0.76, 95% CI 0.54–1.05, p = 0.10) showed a trend toward improved CSS. Compared with squamous histology, micropapillary tumors were associated with lower mortality (aHR 0.55, 95% CI 0.43–0.69, p < 0.001). In logistic regression, NH Asian/PI patients had higher odds of high-risk variant presentation (OR 1.71, 95% CI 1.08–2.71, p = 0.021), while NH Black (OR 0.67, 95% CI 0.44–1.01, p = 0.058) and Hispanic (OR 0.76, 95% CI 0.48–1.21, p = 0.24) groups did not differ significantly. Conclusions: Among patients with variant histology bladder cancer, NH Black individuals experience significantly worse cancer-specific survival despite adjustment for subtype, stage, SES, and rurality, suggesting inequities beyond tumor biology. NH Asian/PI patients more often present with aggressive variants but do not exhibit excess mortality, highlighting possible differences in access or treatment delivery. Efforts to address structural and care-related disparities remain essential for improving outcomes in this rare, high risk bladder cancer population.