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dc.contributor.authorCallender, Ten_US
dc.contributor.authorEmberton, Men_US
dc.contributor.authorMorris, Sen_US
dc.contributor.authorEeles, Ren_US
dc.contributor.authorEeles, Ren_US
dc.contributor.authorKote-Jarai, Zen_US
dc.contributor.authorPharoah, PDPen_US
dc.contributor.authorPashayan, Nen_US
dc.identifier.citationPLoS medicine, 2019, 16 (12), pp. e1002998 - ?en_US
dc.description.abstract<h4>Background</h4>The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening.<h4>Methods and findings</h4>A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose.<h4>Conclusions</h4>Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness.en_US
dc.format.extente1002998 - ?en_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectProstate-Specific Antigenen_US
dc.subjectMass Screeningen_US
dc.subjectLife Tablesen_US
dc.subjectRisk Assessmenten_US
dc.subjectQuality-Adjusted Life Yearsen_US
dc.subjectMiddle Ageden_US
dc.subjectCost-Benefit Analysisen_US
dc.subjectEarly Detection of Canceren_US
dc.titlePolygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPLoS medicineen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorKote-Jarai, Zsofiaen_US
dc.contributor.icrauthorEeles, Rosalinden_US

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