{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:30:29Z","timestamp":1789421429651,"version":"build-2803163510"},"reference-count":33,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Emerging evidence suggests that\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              inactivation may be a strong predictor of poor survival for men with prostate cancer (PC); however, large-scale validation is lacking.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              We analyzed whether\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alterations are associated with inferior survival in advanced PC and evaluated the impact of co-occurring genomic alterations on outcomes using retrospective data from the Veteran's Health Administration and Veterans Affairs Multi-Omics Analysis Platform for Prostate Cancer from 2016 to 2023.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              The primary outcome was overall survival (OS) from onset of metastatic castration-resistant prostate cancer (mCRPC), as well as OS from initiation of life-prolonging therapy other than androgen deprivation therapy, and time to development of mCRPC. Eighty-seven (3.5%) of the 2,512 included patients had an\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alteration detected. The median age at diagnosis in the\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              -altered group was 71 (IQR, 65-76) years, and 68 (IQR, 62-73) years in the\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              wild-type group. The median overall survival from diagnosis of mCRPC was 1.31 years (95% CI, 0.89 to 1.84) in those with an\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alteration compared with 2.99 years (95% CI, 2.79 to 3.23).\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alteration alone conferred similar poor prognosis when compared with patients who had combined\n              <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              alterations. A dose effect was seen with increasing numbers of tumor suppressor genes (TSGs\u2014\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n              ) conferring poorer outcomes. The median survival of patients from diagnosis of mCRPC with zero, one, two, and three TSGs was 3.74, 2.61, 1.61, and 0.87 years, respectively.\n              <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n              alterations were not associated with significantly worse outcomes unless accompanied by\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alteration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              In this large, real-world cohort of men with mCRPC,\n              <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n              alterations emerged as a strong indicator of poor prognosis and can be used to stratify studies alone or in conjunction with other TSG alterations.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-25-00341","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T19:59:08Z","timestamp":1758311948000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Prognostic Significance of\n            <i>RB1<\/i>\n            Alterations on Outcomes in Metastatic Prostate Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-4954","authenticated-orcid":true,"given":"Ruben","family":"Raychaudhuri","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, University of Washington, VA Puget Sound HCS, Seattle, WA"},{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isla P.","family":"Garraway","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, CA"},{"name":"VA Greater Los Angeles Healthcare System, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara N.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Rettig","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, CA"},{"name":"VA Greater Los Angeles Healthcare System, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6388-5553","authenticated-orcid":true,"given":"Martin W.","family":"Schoen","sequence":"additional","affiliation":[{"name":"Saint Louis Veterans Affairs Medical Center, Saint Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Washington, VA Puget Sound HCS, Seattle, WA"},{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-2226","authenticated-orcid":true,"given":"Himisha","family":"Beltran","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5451-5726","authenticated-orcid":true,"given":"Peter S.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Washington, VA Puget Sound HCS, Seattle, WA"},{"name":"Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4459-0295","authenticated-orcid":true,"given":"Bruce","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Washington, VA Puget Sound HCS, Seattle, WA"},{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, 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