{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:08:35Z","timestamp":1786975715828,"version":"build-2736575974"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n National guidelines recommend next-generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. Non-Hispanic Black men are poorly represented in precision oncology cohorts, and therefore differences in alterations frequencies between non-Hispanic Black and White men remain poorly characterized.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race and ethnicity and overall survival in US veterans.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study compared alteration frequencies between non-Hispanic Black and White men who underwent NGS testing from January 23, 2019, to November 2, 2023, adjusted by NGS analyte and clinicopathologic covariates. The analytic data file was locked on December 8, 2023. NGS testing was performed through the Department of Veterans Affairs (VA) National Precision Oncology Program, part of the largest near-equal access integrated health care system in the US.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Pathogenic alterations identified by NGS testing with a commercially available NGS platform.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome consisted of alteration frequencies in individual genes, actionable targets, and canonical prostate cancer pathways. Associations between alteration frequency and race and ethnicity as well as survival were also examined.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 5015 veterans with mPCa who underwent NGS were included (1784 non-Hispanic Black [35.6%] and 3231 non-Hispanic White [64.4%]; mean [SD] age, 67.4 [9.0] years). Non-Hispanic Black veterans were younger, had higher prostate-specific antigen levels at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared with non-Hispanic White veterans. Nine of the top 10 most commonly altered genes were the same in non-Hispanic Black and non-Hispanic White veterans; however, the frequencies of alterations varied by race and ethnicity. Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in\n SPOP<\/jats:italic>\n (odds ratio [OR], 1.7; 95% CI, 1.2-2.6) as well as immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5) including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4). Furthermore, non-Hispanic Black race and ethnicity was associated with lower odds of genomic alterations in the\n AKT\/PI3K<\/jats:italic>\n pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8). Cox proportional hazards modeling stratified by race and ethnicity found that alterations in tumor suppressor genes, including\n TP53,<\/jats:italic>\n were associated with shorter overall survival in both non-Hispanic Black (hazards ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This retrospective clinical genomic profiling cohort study with a large total and proportional representation of non-Hispanic Black men with mPCa reported significant differences in alteration frequencies from key oncogenic pathways but similar survival rates in the near equal-access VA health care setting. This analysis suggests the utility of genomic testing for identifying candidates irrespective of race and ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.9119","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T11:00:57Z","timestamp":1747047657000},"page":"e259119","source":"Crossref","is-referenced-by-count":12,"title":["Somatic Tumor Next-Generation Sequencing in US Veterans With Metastatic Prostate Cancer"],"prefix":"10.1001","volume":"8","author":[{"given":"Luca F.","family":"Valle","sequence":"first","affiliation":[{"name":"Radiation Oncology Service, Veterans Affairs (VA) Greater Los Angeles Healthcare System, Los Angeles, California"},{"name":"Department of Radiation Oncology, UCLA (University of California, Los Angeles), Los Angeles"},{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. 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Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent S.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences, University of California, San Diego, School of Medicine, La Jolla"},{"name":"Veterans Health Administration San Diego Health Care System, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Rettig","sequence":"additional","affiliation":[{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California"},{"name":"Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California"},{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles"},{"name":"Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Nickols","sequence":"additional","affiliation":[{"name":"Radiation Oncology Service, Veterans Affairs (VA) Greater Los Angeles Healthcare System, Los Angeles, California"},{"name":"Department of Radiation Oncology, UCLA (University of California, Los Angeles), Los Angeles"},{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California"},{"name":"Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isla P.","family":"Garraway","sequence":"additional","affiliation":[{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California"},{"name":"Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles"},{"name":"Department of Surgical and Perioperative Care, VA Greater Los Angeles Healthcare System, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosj","family":"Yamoah","sequence":"additional","affiliation":[{"name":"Radiation Oncology Service, James Haley VA Medical Center, Tampa, Florida"},{"name":"Department of Radiation Oncology, H. 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