{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:45:39Z","timestamp":1792183539410,"version":"4.4.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      mutation testing identifies patients with metastatic castration-resistant prostate cancer (mCRPC) eligible for poly(ADP-ribose) polymerase inhibitors; however, clinical outcomes remain heterogeneous within these genotypes. We evaluated whether plasma-derived genomic instability status (GIS) was associated with outcomes beyond\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PALB2<\/jats:italic>\n                      mutation status in the phase II TRITON2 study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective biomarker analysis included TRITON2 patients with available baseline plasma profiled using Guardant360 Liquid. GIS is a probabilistic measure of homologous recombination deficiency (HRD) inferred from genome-wide copy number variants and somatic mutational signatures. Analyses were restricted to patients with baseline tumor fraction (TF) \u2265 25%. Radiographic progression-free survival (rPFS) was analyzed using Kaplan-Meier methods and Cox models adjusted for age and baseline TF. Secondary end points included objective response rate (ORR), serum prostate-specific antigen (PSA50) declines, and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 104 patients with TF \u2265 25%, 43 (41%) had GIS detected. Compared with GIS detected, absence of GIS was associated with shorter rPFS (hazard ratio [HR], 2.81 [95% CI, 1.61 to 4.93];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;.001). Joint stratification demonstrated patients with both GIS detected and\n                      <jats:italic toggle=\"yes\">BRCA\/PALB2<\/jats:italic>\n                      mutation experienced the longest rPFS, whereas absence of GIS was associated with shorter rPFS regardless of\n                      <jats:italic toggle=\"yes\">BRCA\/PALB2<\/jats:italic>\n                      mutation status. In\n                      <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n                      -mutated patients, rPFS trended being longer in those with GIS detected (compared with those without GIS detected; HR, 2.02 [95% CI, 0.95 to 4.29];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .069), with numerically higher ORR (25.7%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      14.3%) and PSA50 response rate (65.7%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      42.9%). No statistically significant differences in OS were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma-derived GIS was associated with improved rPFS and higher response rates in rucaparib-treated patients and further stratified outcomes within mutation-defined populations. These findings support genomic instability assessment as a complementary biomarker to mutation testing and warrant prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00390","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:59:09Z","timestamp":1792180749000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Plasma-Derived Genomic Instability Status and Rucaparib Outcomes in Metastatic Castration-Resistant Prostate Cancer: TRITON2"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9006-7043","authenticated-orcid":true,"given":"Wassim","family":"Abida","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-3895","authenticated-orcid":true,"given":"Alan H.","family":"Bryce","sequence":"additional","affiliation":[{"name":"City of Hope, Goodyear, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-0208","authenticated-orcid":true,"given":"Akash","family":"Patnaik","sequence":"additional","affiliation":[{"name":"University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4223-2905","authenticated-orcid":true,"given":"Brooke","family":"Overstreet","sequence":"additional","affiliation":[{"name":"Guardant Health, Redwood City, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9998-7543","authenticated-orcid":true,"given":"Matthew","family":"Margolis","sequence":"additional","affiliation":[{"name":"Guardant Health, Redwood City, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7852-5893","authenticated-orcid":true,"given":"Pegah","family":"Safabakhsh","sequence":"additional","affiliation":[{"name":"Guardant Health, Redwood City, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-9474","authenticated-orcid":true,"given":"Karim","family":"Fizazi","sequence":"additional","affiliation":[{"name":"Oscar Lambret Centre, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.01.015"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.09.017"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603144"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.6760"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.08.004"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01035"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.05.021"},{"key":"e_1_3_10_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13585"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0394"},{"key":"e_1_3_10_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911440"},{"key":"e_1_3_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.02.002"},{"key":"e_1_3_10_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2135"},{"key":"e_1_3_10_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-00731-4"},{"key":"e_1_3_10_15_2","article-title":"Genomic features and response to poly (ADP-ribose) polymerase inhibition in metastatic castration-resistant prostate cancer","author":"Chang JCW","unstructured":"Chang JCW, Nandakumar S, Stopsack KH, et al: Genomic features and response to poly (ADP-ribose) polymerase inhibition in metastatic castration-resistant prostate cancer. JCO Precis Oncol 10.1200\/PO-25-00934","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_10_16_2","doi-asserted-by":"crossref","unstructured":"Safabakhsh P Tolkunov D Lai J et al: HRD status prediction in patients with advanced breast prostate ovarian and pancreatic cancers using a liquid biopsy assay. Presented at: 2025 ASCO Annual Meeting; Chicago IL. Abstract 3047","DOI":"10.1200\/JCO.2025.43.16_suppl.3074"},{"key":"e_1_3_10_17_2","doi-asserted-by":"crossref","unstructured":"Jiang T Wu I Kim Y et al: Analytical validation of a robust integrated genomic and epigenomic liquid biopsy for biomarker discovery therapy selection and response monitoring. 2023. Presented at: AACR Annual Meeting; Abstract 6601","DOI":"10.1158\/1538-7445.AM2023-6601"},{"key":"e_1_3_10_18_2","unstructured":"Greenwald WY Gross A Jiang T et al: Accurate epigenomic estimates of circulating tumor fraction in large-scale clinical data. 2022. Presented at: AACR Annual Meeting; Abstract 5189"},{"key":"e_1_3_10_19_2","doi-asserted-by":"crossref","unstructured":"Gross A Zhao J Quinn K et al: Landscape of epigenomic tumor fraction in large pan-cancer cfDNA cohort. 2025. Presented at: AACR Annual Meeting; Abstract 5936","DOI":"10.1158\/1538-7445.AM2025-5936"},{"key":"e_1_3_10_20_2","doi-asserted-by":"crossref","unstructured":"Fiaux PC Cai M Safabakhsh P et al: Analytical validation of a new plasma-only bioinformatics classifier to identify variants from clonal hematopoiesis in cfDNA liquid biopsy assays. 2025. Presented at: AACR Annual Meeting; Abstract 6603","DOI":"10.1158\/1538-7445.AM2025-6603"},{"key":"e_1_3_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1943-3"},{"key":"e_1_3_10_22_2","doi-asserted-by":"crossref","unstructured":"Liang SI Quandt Z Wienke S et al: Methylation-based ctDNA tumor fraction changes predict long-term clinical benefit from immune checkpoint inhibitors in RADIOHEAD a Real-World Pan-Cancer Study. Cancer Res Commun 5:1384-1395 2025","DOI":"10.1158\/2767-9764.CRC-25-0151"},{"key":"e_1_3_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlb.2025.100442"},{"key":"e_1_3_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00382-0"},{"key":"e_1_3_10_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00683-X"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-26-00390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:59:15Z","timestamp":1792180755000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-26-00390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1200\/PO-26-00390"],"URL":"https:\/\/doi.org\/10.1200\/po-26-00390","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2600390"}}