BACKGROUND: Bladder cancer genomics are poorly understood, limiting targeted or personalized approaches to treatment. We sought to characterize genomic profiles and clinical outcomes in patients undergoing radical cystectomy for bladder cancer at an early age.
METHODS: We selected patients from an institutional database who were under the age of 55 and undergoing radical cystectomy for bladder cancer between 2008 and 2023. Diagnosis was confirmed and clinical outcomes were obtained using manual chart review. Cystectomy samples from institutional tissue bank were sequenced, and a preliminary cohort of 17 patients underwent genomic profiling with targeted next-generation sequencing (OncoPanel). Kaplan-Meier survival analysis, Chi-square, and Kruskal-Wallis tests were performed.
RESULTS: 134 patients were included. On final pathology, 43% had stage ?T1, 23% stage T2, 25% stage T3, and 9% T4. Most patients were male (84%) and White (96%). There were no significant differences in clinical characteristics or complication rates between age groups. 48.5% were diverted with an ileal conduit and 9% were performed robotically. Median follow-up was 45.8 months. The top 5 most frequently mutated genes (Figure 1A) were TP53 (65%), KMT2D (35%), KDM6A (24%), RB1 (24%), and ARID1A (18%). Survival analysis of the preliminary cohort by KMT2D mutation status appeared to be associated with worse Progression Free Survival (HR 1.26) though this association was not statistically significant likely due to the small number of patients (Figure 1B).
CONCLUSIONS: Our preliminary results suggest KMT2D, a known tumor suppressor and chromatin-remodeling protein associated with aggressive tumor characteristics, may play an important role in this population given its over-representation in the youngest patients. Additional sequencing of a larger patient population is needed to confirm and further refine these findings.
