{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:27:46Z","timestamp":1787956066897,"version":"build-2784847793"},"reference-count":79,"publisher":"Harborside Press, LLC","issue":"2D","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic <jats:italic>BRCA<\/jats:italic> testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria\/family history (FH)\u2013based germline <jats:italic>BRCA<\/jats:italic> testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. <jats:bold>Methods:<\/jats:bold> Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic <jats:italic>BRCA<\/jats:italic> testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria\/FH-based germline <jats:italic>BRCA<\/jats:italic> testing (strategy B). Unaffected relatives with germline <jats:italic>BRCA1\/BRCA2\/RAD51C\/RAD51D\/BRIP1<\/jats:italic> PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer\/societal perspectives, along with probabilistic\/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with \u00a330,000\/QALY (UK) and $100,000\/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. <jats:bold>Results:<\/jats:bold> Compared with clinical criteria\/FH-based <jats:italic>BRCA<\/jats:italic> testing, <jats:italic>BRCA1\/BRCA2\/RAD51C\/RAD51D\/BRIP1<\/jats:italic> germline testing and <jats:italic>BRCA1\/BRCA2<\/jats:italic> somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of \u00a351,175\/QALY (payer perspective) and \u00a350,202\/QALY (societal perspective) and a US ICER of $175,232\/QALY (payer perspective) and $174,667\/QALY (societal perspective), above UK\/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of \u00a311,291\/QALY or $68,808\/QALY and societal-perspective ICERs of \u00a36,923\/QALY or $65,786\/QALY. One year\u2019s testing could prevent 209 UK BC\/OC cases and 192 deaths, and 560 US BC\/OC cases and 460 deaths. <jats:bold>Conclusions:<\/jats:bold> Unselected panel germline and somatic <jats:italic>BRCA<\/jats:italic> testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace <jats:italic>BRCA<\/jats:italic> testing alone.<\/jats:p>","DOI":"10.6004\/jnccn.2023.7331","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T15:12:45Z","timestamp":1713453165000},"source":"Crossref","is-referenced-by-count":6,"title":["Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer"],"prefix":"10.6004","volume":"22","author":[{"given":"Ranjit","family":"Manchanda","sequence":"first","affiliation":[{"name":"Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK"},{"name":"Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK"},{"name":"Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK"},{"name":"MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, London, UK"},{"name":"Department of Gynecology, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK"},{"name":"Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Sobocan","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK"},{"name":"Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK"},{"name":"Division of Gynecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel V.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wei","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK"},{"name":"Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin","family":"Kalra","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK"},{"name":"Department of Gynecological Oncology, Barts Health NHS Trust, Royal London 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Sciences, University of Glasgow, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanthini M.","family":"Crusz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lockley","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveena","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Barts Health NHS Trust, London, 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Mills-Baldock","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"El-Khouly","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wallace","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Division of Evolution, Infection, and Genomic Sciences, University of Manchester, Manchester, 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