Polygenic Risk Score and Tumor Upgrading in Patients Receiving Active Surveillance

Dr. Catalona and his collaborators studied the associations between the patient’s germline genomic polygenic risk score (PRS) and prostate cancer tumor upgrading and tumor features in men enrolled in an active surveillance program.1 They used the new PRS consisting of 451 prostate cancer inherited genomic risk variants and a PRS-400 after excluding 50 of the variants that are associated with a man’s normal PSA levels in the absence of prostate cancer. They found that a high PRS was associated with an increased risk of tumor upgrading and other features of the tumor’s biological aggressiveness. Excluding 50 of the PSA variants that determine the man’s “normal” (i.e., not prostrate cancer-produced PSA) from the PRS increased the correlation with tumor aggressiveness. This study shows that a PRS obtained from a saliva or blood sample may be a useful biomarker for patients considering their management with active treatment versus active surveillance and the appropriate intensiveness of the surveillance regimen if they choose surveillance.
Goss LB, et al. JAMA Oncol. 2025; 11(2); 168-171. PMID: 39666350.