Abstract
Purpose:This study aimed to quantify the probability of overdiagnosis of prostate cancer by polygenic risk.Genet Med 17 10, 789–795.Methods:We calculated the polygenic risk score based on 66 known prostate cancer susceptibility variants for 17,012 men aged 50–69 years (9,404 men identified with prostate cancer and 7,608 with no cancer) derived from three UK-based ongoing studies. We derived the probabilities of overdiagnosis by quartiles of polygenic risk considering that the observed prevalence of screen-detected prostate cancer is a combination of underlying incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis.Genet Med 17 10, 789–795.Results:Polygenic risk quartiles 1 to 4 comprised 9, 18, 25, and 48% of the cases, respectively. For a prostate-specific antigen test sensitivity of 80% and MST of 9 years, 43, 30, 25, and 19% of the prevalent screen-detected cancers in quartiles 1 to 4, respectively, were likely to be overdiagnosed cancers. Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between the lowest and the highest polygenic risk quartiles.Genet Med 17 10, 789–795.Conclusion:Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer.Genet Med 17 10, 789–795.
Highlights
The recently updated US Preventive Services Task Force guidelines recommended against serum prostate-specific antigen (PSA)-based screening for prostate cancer on the grounds that the expected harms of screening outweigh the potential benefits.[1]
Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between the lowest and the highest polygenic risk quartiles
Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer
Summary
The recently updated US Preventive Services Task Force guidelines recommended against serum prostate-specific antigen (PSA)-based screening for prostate cancer on the grounds that the expected harms of screening (false-positive findings, overdiagnosis, and overtreatment) outweigh the potential benefits.[1]. This study shows that there is no prostate cancer–related mortality benefit of organized annual screening compared with opportunistic screening.[2] By contrast, the European Randomized Study of Screening for Prostate Cancer involved 182,000 men aged 50 to 74 years randomized to the screening arm and offered PSA testing, on average, every 4 years, or to the control arm with no intervention offered. To prevent one death from prostate cancer, 781 men would need to be invited for screening and 27 additional cancers would need to be detected.[3] These findings indicate that population screening for prostate cancer using PSA can prevent death from the cancer for a subset of men, but at a cost of overdiagnosis and subsequent overtreatment This raises the question of whether targeted screening for prostate cancer can improve the benefit-to-harm ratio of screening
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