Volume-adjusted p2PSA-derived indices for predicting prostate cancer: the PROPHET study

This study aimed to assess the diagnostic value of prostate and transition zone (TZ) volume-adjusted p2PSA-derived indices for detecting any and clinically significant prostate cancer (PCa) in the prospective multicenter PROPHET study.

Among 363 men (median age 68 years, PSA 5.96 ng/mL), total PSA, free PSA, and p2PSA were measured to calculate %p2PSA, p2PSA/%fPSA, and the Prostate Health Index (PHI). Each index was adjusted by prostate or TZ volume. Diagnostic accuracy for any PCa and clinically significant PCa (csPCa) was evaluated using the area under the receiver operating characteristic curve (AUC), partial AUC (> 90% sensitivity), specificity, positive predictive value, negative predictive value, and false-positive rate.

PCa was detected in 179 men (49.3%). For predicting any PCa, PHI density and TZ volume-adjusted PHI showed AUCs of 0.797 and 0.788 with false-positive rates of 50.5%. For csPCa defined as > 2 positive cores or Gleason Grade Group ≥ 2-3, AUCs were 0.807-0.823 and false-positive rates 42.0-47.5%. Both indices enabled biopsy avoidance in 49-58% of men without csPCa while maintaining 90% sensitivity. The diagnostic performance of PHI density and TZ volume-adjusted PHI was statistically superior to PSA density and TZ volume-adjusted PSA, demonstrating improved discriminative ability at key clinical thresholds.

Volume-adjusted p2PSA-derived indices demonstrated improved diagnostic performance and may reduce unnecessary biopsies. Their validation in a PHI-independent prospective design supports robust clinical applicability.