PROSTest, a Multigene Liquid Biopsy Signature, Effectively Stratifies Patients With High PSA for Prostate Biopsy.

backgroundProstate-specific antigen (PSA) remains the standard biomarker for prostate cancer (PCa) detection, but its limited specificity-particularly in the 3-10 ng/mL range-leads to overdiagnosis and unnecessary biopsies. Including multiparameteric MRI (mpMRI) helps to reduce the number of PSA-false-positive biopsies, but there is still a need for noninvasive diagnostics that improve risk stratification and reduce unnecessary interventions.

methodsPROSTest is a peripheral blood-based assay that quantifies a 27-gene signature in the androgen receptor (AR) signaling pathway in addition to 3 housekeeping genes (HKGs). PCR results are fed into a proprietary machine learning (ML) algorithm to produce a numerical score on a scale of 0-100 with a clinically validated cutoff of 50 for a final binary readout; positive or negative for likelihood of cancer on biopsy. In this report, the diagnostic performance of PROSTest was evaluated in 1,894 male subjects including 970 individuals with actionable results (PSA ≥ 3.0 ng/mL). We focused on two PSA-graded intended-use populations: subjects aged ≥ 45 years with PSA 3-10 ng/mL (n = 467), and those with PSA > 10 ng/mL (n = 503). PSA and PROSTest were conducted on all subjects.

resultsIn the 970 cohort, adding the PROSTest achieved an AUC of 0.96 and was significantly more accurate than PSA alone for differentiating PCa from benign prostatic disease (Chi

conclusionsPROSTest demonstrates improved stratification value relative to PSA and could significantly reduce PSA-driven false positive biopsies. Out of 259 non-PCa subjects biopsied based on high PSA levels, applying PROSTest could potentially eliminate 227 biopsies (87.6%). PROSTest superior NPV was not confounded as a tradeoff for the PPV as PROSTest exhibited a sensitivity of ~95% (675/711 PCa detected).