Abstract 2415: Polygenic risk-tailored screening for prostate cancer: A cost-effectiveness analysis
Authors: Callender Thomas , Emberton Mark , Morris Steve , Eeles Ros , Kote-Jarai Zsofia , Pharoah Paul , Pashayan Nora 
Published: August 2019

Abstract
Background Screening for prostate cancer with prostate specific antigen (PSA) remains controversial. Risk-tailoring based on age and polygenic profile might conserve the benefits of PSA screening whilst reducing overdiagnosis. This study evaluates the cost-effectiveness and benefit-to-harm balance of polygenic risk-tailored screening for prostate cancer.
Methods A life-table approach was used. A hypothetical cohort of 4.48 million men in England between the ages of 55 and 70 was followed to the age of 90. Three scenarios were compared: no screening, age-based screening (PSA testing every four years from 55 to 70), and risk-tailored screening based on age and polygenic risk profile (men above the risk threshold receive PSA testing four-yearly from the age they reach the risk threshold to 70). The number of prostate cancer cases, deaths from prostate cancer, overdiagnosed cases, life-years and quality-adjusted life-years (QALYs), incremental cost per QALY, and net monetary benefit were calculated. Sensitivity analyses investigated the impact of parameter uncertainty, and the impact of varying the risk threshold, on outcomes. Costs were estimated from the perspective of the UK National Health Service; both costs and benefits were discounted at 3.5%.
Results The incremental cost per additional QALY for age-based screening compared to no screening was £58,254 ($75,899), with 27% simulations having an incremental cost-effectiveness ratio of less than £20,000 ($26,058), the threshold set by the UK National Institute for Health and Care Excellence for an intervention to be considered cost-effective. In risk-tailored screening, as the 10-year absolute risk-threshold was progressively increased from 2.6%, equivalent to the 10-year absolute risk of a 55-year old man, to 7.1%, the corresponding risk of a 69-year old man, the cost per additional QALY gained reduced from £36,065 ($46,989) to £26,210 ($34,149), when compared to no screening. By comparison with age-based screening, risk-tailored screening with a threshold between 2.6% and 7.1% led to 8 (2.5%) and 45 (13%) fewer deaths prevented from prostate cancer per 10,000 men, with a 0.1% rise and 10% reduction in costs, respectively. Raising the risk threshold from 2.6% to 7.1% led to fewer men being screened (cumulative total of 35% of men screened by comparison with 83%), 53% fewer overdiagnosed cases, 22% fewer biopsies and 10% lower costs, at the expense of 10% fewer prostate cancer deaths averted.
Conclusion Risk-tailored screening reduces the harms of screening for prostate cancer whilst preserving much of the mortality benefit. This study raises the prospect of risk-tailored population-based screening for prostate cancer; the precise risk-thresholds selected will depend on societal judgements regarding the appropriate trade-offs between harms and benefits.
Citation Format: Thomas Callender, Mark Emberton, Steve Morris, Ros Eeles, Zsofia Kote-Jarai, Paul Pharoah, Nora Pashayan. Polygenic risk-tailored screening for prostate cancer: A cost-effectiveness analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2415.