Sex Disparity in Non-muscle-invasive Bladder Cancer: Pitfalls of Large Population-based Data Sets and Lessons from an Integrated Analysis

The impact of sex on non-muscle-invasive bladder cancer (NMIBC) remains uncertain and current evidence is conflicting. To address this uncertainty, we conducted an integrative analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare and UROMOL data sets to explore sex disparities in NMIBC oncological outcomes. In the SEER-Medicare cohort, females had lower risks of recurrence and progression in comparison to males, but no significant difference in BC-specific mortality was observed. Analysis of the UROMOL cohort revealed no sex-specific differences in tumour biology across genomic, transcriptomic, and spatial proteomic domains. These findings highlight the limitations of relying on just SEER-Medicare data for NMIBC, for which identification of the true incidence of recurrence and progression is challenging, and emphasise the importance of combining population-based data and molecular biology results to gain a comprehensive understanding of NMIBC. PATIENT SUMMARY: The impact of sex on non-muscle-invasive bladder cancer (NMIBC) outcomes is unclear. Our analysis of a large population-based data set showed that the risks of recurrence and progression were lower for females. However, analysis of a separate molecular dataset showed no sex-specific differences. The results highlight the importance of combining population-based data and molecular biology results for a better understanding of NMIBC.