Abstract 4681: Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish arm of the European randomised study of screening for prostate cancer (ERSPC)

Abstract

Abstract Background The US Preventive Services Task Force (USPSTF) recommends against serum prostate specific antigen (PSA) based screening for prostate cancer, on the grounds that the expected harms of screening (mainly overdiagnosis and subsequent overtreatment) outweigh the potential benefits (mainly reduction in cancer-specific mortality). This study aims to estimate the mean sojourn time (MST) and sensitivity and then use these estimates to derive the probability of overdiagnosis by polygenic risk group. Methods We calculated the polygenic risk score based on genotypes of 66 known prostate cancer susceptibility variants for 4,967 men from the Finnish arm of the European randomised study of screening for prostate cancer (ERSPC). We stratified the 80,179 Finnish trial participants into two risk groups below and above 50th percentile risk. Using a maximum likelihood method based on interval cancers, we estimated the MST and episode sensitivity. We calculated the expected number of non-overdiagnosed screen-detected cancers over three rounds of screening. We estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers. We derived overall and separate estimates of overdiagnosis by polygenic risk group. Result Men in the above average genetic risk group accounted for 74 percent of the prostate cancers cases. The episode sensitivity was 0.55 (95% CI 0.45 to 0.65) and MST 6.3 (95% CI 4.2 to 8.3) years. The overall overdiagnosis was 42% (95% CI 37 to 52) with 58% (95% CI 54 to 65) in the lower risk group and 37% (95% CI 31 to 47) in the higher risk group. Targeting screening to men in the higher polygenic risk group would reduce screening episodes by half while detecting 80% of the non-overdiagnosed cancers and preventing 38% of the overdiagnosed cancers at a cost of missing 20% of the non-overdiagnosed cancers. Conclusion Polygenic risk-stratified screening for prostate cancer is a promising approach to decrease overdiagnosis. Further research is needed to study the effect of targeted screening on cancer-specific mortality. Citation Format: Nora Pashayan, Paul D.P. Pharoah, Johanna Schleutker, Kirsi Talala, Teuvo LJ Tammela, Liisa Määttänen, Patricia Harrington, Jonathan Tyrer, Rosalind Eeles, Stephen W. Duffy, Anssi Auvinen. Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish arm of the European randomised study of screening for prostate cancer (ERSPC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4681. doi:10.1158/1538-7445.AM2015-4681