{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:57:44Z","timestamp":1784185064355,"version":"3.55.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-22-1-0602"],"award-info":[{"award-number":["W81XWH-22-1-0602"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Prostate Cancer Foundation Igor Tulchinsky"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor suppressor gene (TSG) alterations prognosticate inferior survival in metastatic hormone-sensitive prostate cancer (mHSPC) and may affect response to therapy. We evaluated the association of TSG alterations with overall survival (OS) in mHSPC, stratified by initial treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified veterans with de novo mHSPC diagnosed from 2017 to 2023 within the Veterans Health Administration. TSG alterations included loss-of-function alterations in RB1, TP53, and PTEN identified by somatic sequencing through the National Precision Oncology Program. Treatments within 4\u2009months of diagnosis included androgen deprivation therapy (ADT), docetaxel, and androgen receptor pathway inhibitors (ARPIs). Kaplan\u2013Meier and Cox models evaluated relationships between TSG alterations, clinical factors, and OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1842 veterans who met criteria, 865 had sequencing within 6 months. TSG alterations were found in 935 veterans, with the most common alterations being TP53 (36.7%), PTEN (23.4%), and RB1 (4.5%). In veterans sequenced within 6\u2009months, RB1, TP53, and PTEN alterations were associated with mortality with a hazard ratio (95% CI) of 2.86 (1.94-4.21) (P\u2009&amp;lt;\u2009.001), 1.64 (1.30-2.05) (P\u2009&amp;lt;\u2009.001), and 1.52 (1.20-1.91) (P\u2009&amp;lt;\u2009.001), respectively. In the same cohort, median OS (95% CI) was 40.7\u2009months (37.5-NR) with no alterations, 34.1\u2009months (30.3-37.3) with 1, and 19.7\u2009months (16.5-25.5) with \u22652 TSG alterations. In veterans with \u22651 alteration and sequencing within 6 months, combination therapy with ARPIs was associated with decreased mortality, aHR (95% CI) of 0.65 (0.48-0.88, P\u2009=\u2009.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TSG alterations were associated with inferior OS in veterans with mHSPC. In this real-world observational study, ARPI-based combination therapy in veterans with TSG alterations was associated with the longest survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag033","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:33:34Z","timestamp":1770122014000},"source":"Crossref","is-referenced-by-count":1,"title":["Tumor suppressor genes, treatments, and survival in US veterans with prostate cancer"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-0356","authenticated-orcid":false,"given":"Krishny","family":"Karunanandaa","sequence":"first","affiliation":[{"name":"Saint Louis University School of Medicine Department of Medicine, , St. Louis, MO 63104,","place":["United States"]},{"name":"Veterans Affairs Saint Louis Medical Center Research Service, , St. Louis, MO, St. Louis, MO 63110,","place":["United 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Seattle, WA 98109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eaton","sequence":"additional","affiliation":[{"name":"Veterans Affairs Saint Louis Medical Center Research Service, , St. Louis, MO, St. Louis, MO 63110,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1129-4636","authenticated-orcid":false,"given":"Isla P","family":"Garraway","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System Research Service, , Los Angeles, CA 90073,","place":["United States"]},{"name":"David Geffen School of Medicine at UCLA Jonsson Comprehensive Cancer Center, , Los Angeles, CA 90095,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B","family":"Rettig","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System Research 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