Prognostic utility of tumor mutational burden in older adults (≥75 years) with bladder cancer: A TCGA geriatric oncology analysis.

Abstract

834 Background: Older adults represent nearly half of bladder cancer diagnoses but are underrepresented in biomarker studies. Tumor mutational burden (TMB) is an established predictive biomarker for immunotherapy response, yet its prognostic utility in elderly populations independent of treatment exposure remains unclear. We evaluated the prognostic significance of TMB in patients aged ≥75 years within the treatment naive TCGA BLCA cohort. Methods: Clinical and mutational data from TCGA-BLCA Pan-CanAtlas 2018 were accessed via cBioPortal. The geriatric subgroup was defined as age ≥75 years. TMB was calculated as nonsynonymous mutations per megabase and dichotomized using the standard clinical threshold (≥10 mut/Mb) and a cohort-specific median (5.8 mut/Mb). Cox proportional hazards models were adjusted for age and sex. Because TCGA patients were treatment naive, results reflect TMB as a pure prognostic biomarker. Kaplan-Meier curves were generated for visualization. Results: Of 408 eligible patients, 133 (32.5%) were ≥75 years, with 66 deaths observed. In this subgroup, high TMB defined by median cutoff was significantly associated with improved overall survival (HR 0.44, 95% CI 0.27–0.73; p = 0.002). The ≥10 mut/Mb cutoff showed a favorable but nonsignificant trend (HR 0.61, p = 0.186). TP53 mutation status was not prognostic (p > 0.2). Each additional year of age above 75 remained associated with increased mortality risk (HR 1.08, p = 0.024). Sex was not associated with survival. Conclusions: In patients aged ≥75 years with bladder cancer, elevated TMB remains independently associated with improved overall survival, even in the absence of immunotherapy. These findings suggest that age-related immune senescence does not eliminate the prognostic relevance of TMB and support further study of TMB driven risk stratification and tumor immunogenicity in geriatric urothelial carcinoma.