Personalizing prostate cancer screening may improve the accuracy of detection
The accuracy of prostate-specific antigen (PSA) screening for prostate cancer can be improved by accounting for genetic factors that cause changes in PSA levels that are not associated with cancer, according to a multi-center study led by UC San Francisco and Stanford University.
In a study published June 1, 2023 in Nature Medicine, UCSF researchers and their collaborators conducted a large genome-wide association study of PSA in more than 95,000 men without diagnosed prostate cancer, which identified over 80 novel PSA-associated variants. They set out to discover whether accounting for genetic factors that cause variations in the levels of PSA that are not attributable to cancer could help improve PSA screening.
The researchers leveraged these new data to build a genome-wide polygenic score for PSA, measuring an individual’s genetic predisposition based on genetic variations.
To examine whether the polygenic score could improve the detection of clinically significant disease and reduce overdiagnosis, the researchers applied the polygenic score correction factor to a real-world Kaiser Permanente cohort and estimated the effects of this adjustment on the PSA thresholds used for biopsy referrals.
Applying a correction to PSA levels improved the accuracy of biopsy referral decisions. Roughly 30% of men could have avoided biopsy, though adjusted PSA levels would have missed approximately 9% of positive biopsies. Most of the latter cancers were low-grade disease that did not require treatment, but there remains room to improve the polygenic score.
