{
  "abstract": "Purpose\n\nBRCA1/2 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 BRCA1/2 and PALB2 mutation status in the phase II TRITON2 study.Methods\n\nThis 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) ≥ 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).Results\n\nAmong 104 patients with TF ≥ 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]; P <.001). Joint stratification demonstrated patients with both GIS detected and BRCA/PALB2 mutation experienced the longest rPFS, whereas absence of GIS was associated with shorter rPFS regardless of BRCA/PALB2 mutation status. In BRCA2-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]; P = .069), with numerically higher ORR (25.7% v 14.3%) and PSA50 response rate (65.7% v 42.9%). No statistically significant differences in OS were observed.Conclusion\n\nPlasma-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.",
  "abstract_shown": true,
  "affiliations": [
    "Memorial Sloan Kettering Cancer Center, New York, NY.",
    "City of Hope, Goodyear, AZ.",
    "Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.",
    "University of Chicago, Chicago, IL.",
    "Guardant Health, Redwood City, CA.",
    "Oscar Lambret Centre, Lille, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wassim Abida",
      "orcid": "0000-0002-9006-7043"
    },
    {
      "affs": [
        1
      ],
      "name": "Alan H Bryce",
      "orcid": "0000-0002-0206-3895"
    },
    {
      "affs": [
        2
      ],
      "name": "Simon Chowdhury"
    },
    {
      "affs": [
        3
      ],
      "name": "Akash Patnaik",
      "orcid": "0000-0001-5306-0208"
    },
    {
      "affs": [
        4
      ],
      "name": "Brooke Overstreet",
      "orcid": "0009-0001-4223-2905"
    },
    {
      "affs": [
        4
      ],
      "name": "Matthew Margolis",
      "orcid": "0000-0001-9998-7543"
    },
    {
      "affs": [
        4
      ],
      "name": "Pegah Safabakhsh",
      "orcid": "0009-0007-7852-5893"
    },
    {
      "affs": [
        5
      ],
      "name": "Karim Fizazi",
      "orcid": "0000-0002-6068-9474"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsgqqag1fj58g.bib",
  "cited_by": 0,
  "doi": "10.1200/po-26-00390",
  "fulltext_url": "https://europepmc.org/articles/PMC13704698",
  "id": "dsgqqag1fj58g",
  "issns": [
    "2473-4284"
  ],
  "landing_url": "https://europepmc.org/article/MED/42886888",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|PARP inhibition in cancer therapy"
    ]
  ],
  "openalex": "W7222753895",
  "pdf_url": "https://europepmc.org/articles/PMC13704698?pdf=render",
  "pmcid": "PMC13704698",
  "pmid": "42886888",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dsgqqag1fj58g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42886888",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42886888"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|PARP inhibition in cancer therapy",
      "subfield": "oncology"
    }
  ],
  "title": "Plasma-Derived Genomic Instability Status and Rucaparib Outcomes in Metastatic Castration-Resistant Prostate Cancer: TRITON2.",
  "title_text": "Plasma-Derived Genomic Instability Status and Rucaparib Outcomes in Metastatic Castration-Resistant Prostate Cancer: TRITON2.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/dsgqqag1fj58g",
  "venue": "JCO precision oncology",
  "versions": []
}