N Engl J Med

Polygenic risk score enhances prostate cancer screening accuracy

April 15, 2025

Incorporating a polygenic risk score (PRS) into screening protocols significantly improves the detection of clinically significant prostate cancer compared with PSA or MRI alone, potentially leading to better-targeted interventions and improved patient outcomes.

Study details: In the BARCODE1 trial (NCT03857477), researchers recruited men aged 55 to 69 from U.K. primary care centers using saliva-derived germline DNA to calculate polygenic risk scores (PRS) from 130 variants associated with prostate cancer. Participants in the 90th percentile or higher PRS underwent screening with MRI and transperineal biopsy, regardless of PSA levels.

Results: Out of 40,292 invited, 6,393 had their PRS calculated, and 745 were in the top decile. Among these, 468 underwent MRI and biopsy, detecting prostate cancer in 187 (40%). Of those diagnosed, 103 (55.1%) had intermediate or higher risk cancer per NCCN criteria, and 74 (71.8%) wouldn't have been detected using current U.K. pathways. Additionally, 40 (21.4%) had unfavorable intermediate to very high-risk cancer.

Source:

McHugh JK; BARCODE1 Steering Committee and Collaborators; et al. (2025, April 10). N Engl J Med. Assessment of a Polygenic Risk Score in Screening for Prostate Cancer. https://pubmed.ncbi.nlm.nih.gov/40214032/