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.