Assessment of a Polygenic Risk Score in Screening for Prostate Cancer
Screening using PSA has a high false-positive rate. Genome-wide association studies have identified common germline genetic variants that can be used to calculate a polygenic risk score (PRS) associated with prostate cancer risk. To test the usefulness of a PRS over PSA-based screening, researchers undertook the BARCODE1 study of men aged 55 to 69 years through their primary care clinicians in the UK. PRS were derived from 130 variants in germline DNA extracted from saliva (Dr. Catalona notes that the latest and greatest PRS includes more than 450 genetic variants). Participants with a PRS above the 90th centile were invited for screening using multiparametric MRI scans and transperineal biopsy, irrespective of their PSA result.
Of 40,292 men invited to participate, 8,953 (22.2%) expressed interest and 6,393 had their PRS calculated, of whom 745 (11.7%) had a PRS above 90th centile and were invited for screening. Of these, 468 underwent MRI scanning and prostate biopsy; prostate cancer was detected in 187 (40.0%). Their median age was 64 years. 55.1% were of intermediate or high risk and so required treatment; 70.9% of these cancers would not have been detected using the usual UK prostate cancer diagnostic pathway. Thus PRS can improve the efficiency of prostate cancer screening.
N Engl J Med. 2025 April 10; 392(14): 1406–1417
