Multicenter study of use of a polygenic risk score in screening for prostate cancer

Screening for prostate cancer with a PSA assay has a high rate for false-positive results. Genomewide association studies have identified common germline variants in prostate cancer patients, which can be used to calculate a polygenic risk score (PRS) associated with risk of prostate cancer. The multicenter BARCODE1 trial in the UK derived PRSs from 130 variants in germline DNA extracted from saliva. Participants with a PRS in the 90^th percentile or higher were invited to undergo prostate cancer screening with MRI and transperineal biopsy, irrespective op PSA level. Among 6393 participants, 745 had a PRS in the 90^th percentile or higher, of whom 468 underwent MRI and biopsy; prostate cancer was detected in 187 participants (40.0%). Among these, 103 (55.1%) had intermediate or higher risk requiring treatment; cancer would not have been detected in 74 (71.8%) of these participants according to the current diagnostic pathway in the UK. The authors conclude that in a prostate cancer screening program involving participants in the top decile risk as determined by a PRS, the percentage found to have clinically significant disease was higher than the percentage that would have been identified with the use of PSA or MRI.