{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:11:54Z","timestamp":1790914314820,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      In the PROpel study (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03732820\">NCT03732820<\/jats:ext-link>\n                      ), olaparib plus abiraterone demonstrated statistically significant radiographic progression-free survival benefit versus placebo plus abiraterone in a first-line metastatic castration-resistant prostate cancer (mCRPC) population unselected by homologous recombination repair gene mutation (HRRm) status. From PROpel, we report exploratory biomarker analyses assessing HRRm and\n                      <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                      and\/or\n                      <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n                      (BRCAm) status using tumor tissue and plasma-derived circulating tumor (ct) DNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients received (1:1) either olaparib (300 mg twice a day) or placebo in combination with abiraterone (1,000 mg once daily) plus prednisone\/prednisolone (5 mg twice a day). Tumor tissue and ctDNA samples were analyzed using FoundationOne CDx and FoundationOne Liquid CDx tests, respectively. Biomarker results are presented by individual tests and as an aggregate analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>HRRm status was obtained for 778 of 796 (98%) patients randomly assigned. Aggregating tumor tissue and ctDNA results, 226 patients were identified as having HRRm (including 85 BRCAm). In matched tumor tissue and ctDNA samples (n = 491), and using the tumor tissue result as the reference, high concordance was observed for HRRm (overall percent agreement, 85.1%; negative predictive value, 93.7%) and BRCAm status (overall percent agreement, 93.9%; negative predictive value, 97.3%), with low ctDNA fraction being a limiting factor in rare cases where discordance was observed. Based on the observed agreement, there was a potential incidence of 1% unidentified BRCAm in aggregated non-BRCAm patients (n = 693).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Aggregating tumor tissue and ctDNA analyses maximized the number of patients (98%) with known biomarker status in PROpel while limiting the number of potential false negatives. This represents the most comprehensive means for identifying biomarker-positive and biomarker-negative subgroups and demonstrates the complementary utility of ctDNA testing in mCRPC, particularly when tissue testing is unable to provide a clinically useful result.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01109","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:59:11Z","timestamp":1778529551000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Detection of Homologous Recombination Repair Gene Mutations by Tumor Tissue and Circulating Tumor DNA Testing in Prostate Cancer in the Phase III PROpel Trial"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-1754","authenticated-orcid":true,"given":"Andrew J.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-5617","authenticated-orcid":true,"given":"Fred","family":"Saad","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al\/CRCHUM, Universit\u00e9 de Montreal, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mototsugu","family":"Oya","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-0548","authenticated-orcid":true,"given":"Neal","family":"Shore","sequence":"additional","affiliation":[{"name":"Carolina Urologic Research Center, Myrtle Beach, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-7432","authenticated-orcid":true,"given":"Cagatay","family":"Arslan","sequence":"additional","affiliation":[{"name":"Izmir Economy University Medical Park Hospital, Karsiyaka, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-1831","authenticated-orcid":true,"given":"Niven","family":"Mehra","sequence":"additional","affiliation":[{"name":"Radboud Universitair Medisch Centrum, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Brown","sequence":"additional","affiliation":[{"name":"University Hospital Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Joung","sequence":"additional","affiliation":[{"name":"National Cancer Center, Goyang-si, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-782X","authenticated-orcid":true,"given":"Mikio","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Kagawa University Hospital, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8417-8628","authenticated-orcid":true,"given":"Mustafa","family":"\u00d6zg\u00fcro\u011flu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, Cerrahpa\u015fa School of Medicine, Istanbul University-Cerrahpa\u015fa, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-4352","authenticated-orcid":true,"given":"Craig","family":"Gedye","sequence":"additional","affiliation":[{"name":"Calvary Mater Newcastle, Waratah, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-7343","authenticated-orcid":true,"given":"Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Tulane Medical School, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-3059","authenticated-orcid":true,"given":"Christian","family":"Poehlein","sequence":"additional","affiliation":[{"name":"Merck &amp; 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