Clinical Validation of the Prostate Health Index for Detecting Clinically Significant Prostate Cancer in a Population‐Based Screening Program

Objectives To evaluate the diagnostic performance of the Prostate Health Index (phi) in detecting clinically significant prostate cancer (csPC) among men within the PSA gray zone (2.01–10.00 ng/mL), compared with total PSA and the free‐to‐total PSA ratio (F/T ratio), using a population‐based screening database in Kanazawa city, Japan. Methods Between 2019 and 2023 (excluding 2022), 14 840 men participated in a biennial population‐based prostate cancer screening program in Kanazawa city, Japan. Among them, 2776 men with PSA levels of 2.01–10.00 ng/mL were identified, and 571 men who underwent prostate biopsy were included in the final analysis. The diagnostic accuracy for detecting csPC was compared among PSA, the F/T ratio, and phi using receiver operating characteristic (ROC) and decision curve analyses (DCA). Results The area under the ROC curve (AUC) for detecting csPC was 0.691 for PSA, 0.673 for F/T ratio, and 0.761 for phi. The AUC for phi was significantly higher than that for F/T ratio ( p < 0.05). The DCA demonstrated that phi provided the greatest net benefit across threshold probabilities between 0.2 and 0.6, indicating improved clinical utility for csPC detection in the gray zone. Conclusions In population‐based screening, adding phi to PSA and F/T ratio improved discrimination for csPC and may reduce unnecessary referrals and improve screening efficiency among men in the PSA gray zone.