Abstract A080: Racial disparities in genomic alterations and survival outcomes in prostate cancer: A comparative analysis of Black and White patients using MSK-IMPACT data

Abstract Background: Black men experience higher prostate cancer mortality, yet the genomic drivers of this disparity are incompletely defined. This study examined clinical and molecular differences between Black and White prostate cancer patients using comprehensive sequencing data. Methods: A retrospective analysis of 1,627 patients (130 Black, 1,497 White) from the MSK-IMPACT cohorts (2021, 2024) was conducted using cBioPortal. All had confirmed prostate adenocarcinoma and complete clinical and genomic data, including somatic mutations, copy number alterations, tumor mutational burden (TMB), fraction genome altered (FGA), and microsatellite instability (MSI). Clinical features included age, PSA, Gleason score, and survival. Statistical comparisons used chi-square and Mann-Whitney U tests. Multivariable Cox models adjusted for clinical covariates. Results: Black patients were diagnosed younger (mean 62 vs. 66 years; p 0.001), had higher PSA (165 vs. 87 ng/mL; p 0.001), and more smoking (15% vs. 6.4%; p = 0.004). Median overall survival (OS) was numerically shorter for Black patients (42 vs. 47 months; p = 0.084). Genomic analysis revealed TP53 (32% vs. 20%; p = 0.005), PTEN (23% vs. 10%; p 0.001), and BRCA2 (8% vs. 4%; p = 0.02) mutations were more frequent in White patients. In contrast, RECQL4 (12% vs. 4%; p = 0.001), CDK12 (12% vs. 7%; p = 0.003), and ZFHX3 were more common in Black patients. Race-specific exclusivity patterns were observed: TP53–PTEN and TP53–AR in Black patients, and FOXA1–CDK12, SPOP–TP53 in White patients. In multivariable models, PTEN deletions were strongly associated with worse OS in both groups (Black HR 3.23; p = 0.0043; White HR 1.66; p 0.001). TP53 (HR 1.95; p 0.001) and BRCA2 (HR 1.41; p = 0.022) predicted poor survival in White patients. In Black patients, TP53 and BRCA2 were not statistically significant but trended toward worse outcomes. Pathway analysis showed equal AR pathway involvement, but PI3K/AKT mutations were not significantly present in Black patients and DNA repair pathway mutations were twice as common in White patients. Chromatin remodeling gene alterations were frequent in both groups but differed in composition. OncoPrint visualizations highlighted more complex co-alteration networks in White patients and chromatin remodeling–dominant profiles in Black patients. Conclusions: Black prostate cancer patients present with more aggressive disease and distinct molecular profiles, particularly involving chromatin remodeling and cell cycle genes. These disparities highlight the need for race-aware genomic profiling and equitable access to precision oncology. Citation Format: Chidiebube Ugwu, George Laliotis, Muluken Megiso, Elvis Obomanu, Gabor Varadi. Racial disparities in genomic alterations and survival outcomes in prostate cancer: A comparative analysis of Black and White patients using MSK-IMPACT data abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A080.