Genomic Testing Among Veterans Reveals Racial Differences in Metastatic Prostate Cancer Outcomes

Genomic testing reveals important racial differences in metastatic prostate cancer (mPCa), highlighting the need for precision oncology approaches that account for genetic, clinical, and social factors to improve patient outcomes, according to a study published in JAMA Network Open.

mPCa disproportionately affects non-Hispanic Black men, who face higher incidence and mortality rates compared with non-Hispanic White men. Precision oncology, guided by next-generation sequencing (NGS), offers targeted therapies that can extend survival. Yet Black patients remain underrepresented in genomic studies and less likely to receive testing, limiting equitable access to emerging treatments. Researchers within the Veterans Health Administration’s National Precision Oncology Program (NPOP) examined genomic alterations among more than 5000 veterans with mPCa to address this knowledge gap.

The researchers analyzed tumor and plasma samples from 1784 non-Hispanic Black and 3231 non-Hispanic White veterans diagnosed between January 23, 2019, and November 2, 2023. Non-Hispanic Black patients were younger at diagnosis, had higher prostate-specific antigen (PSA) levels, and were more likely to live in socioeconomically disadvantaged areas.

Unadjusted analyses showed that White veterans more frequently harbored alterations in the AR signaling axis, AKT/PI3K pathway, DNA repair genes, and tumor suppressor genes. By contrast, Black veterans were more likely to exhibit alterations in mismatch repair (MMR) genes, microsatellite instability (MSI), and immunotherapy targets. After adjusting for clinical and demographic factors, these patterns persisted: Black veterans were significantly less likely to have alterations in AR signaling and DNA repair pathways but more likely to carry SPOP mutations and immunotherapy-related targets.

Survival analyses highlighted that different genomic drivers affected mortality risk across racial groups. For White veterans, AR signaling, tumor suppressor, and MMR alterations were associated with worse outcomes. Among Black veterans, TP53 and CDK12 alterations significantly increased the hazard of death.

“While individuals may exhibit different biological aggressiveness and associated outcomes from PCa treatment, precision-based testing and treatment approaches remain critical for personalizing care, optimizing outcomes, informing the design of equitable clinical trials, and narrowing disparities in outcomes for mPCa,” concluded Luca Valle, MD, Radiation Oncology Service, Veterans Affairs (VA) Greater Los Angeles Healthcare System, Department of Radiation Oncology, UCLA (University of California, Los Angeles), UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California, and coauthors.

Reference

Valle LF, Li J, Desai H, et al. Somatic tumor next-generation sequencing in US veterans with metastatic prostate cancer. JAMA Netw Open. 2025;8(5):e259119. doi:10.1001/jamanetworkopen.2025.9119