Prostate Cancer Polygenic Risk Score Associated with Upgrading in Patients on Active Surveillance

Abstract

Active surveillance (AS) is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa). However, AS requires frequent and costly healthcare visits. In a prospective cohort study of 1,220 PCa patients on AS in the Canary Prostate Active Surveillance Study (PASS), we investigated whether polygenic risk scores (PRS) could identify patients who may benefit from intensive vs passive surveillance to reduce these burdens. We constructed a PRS of 451 PCa risk variants (PRS451) in PASS, along with a PRS of 400 variants, excluding 51 prostate-specific antigen (PSA)-associated variants (PRS400) and tested PRS associations with upgrading and extreme upgrading at follow up and prostate volume, PSA, percent of biopsy cores with cancer, and Gleason grade at diagnosis. In AS patients, high PRS was associated with risk of upgrading and possibly tumor multifocality. Excluding PSA variants from the PRS enhanced these associations and revealed an association with smaller prostate size, which has been previously associated with more aggressive tumors. Our findings suggest that PRS may inform intensity of surveillance.