The Percentage of [−2]Pro–Prostate-Specific Antigen and the Prostate Health Index Outperform Prostate-Specific Antigen and the Percentage of Free Prostate-Specific Antigen in the Detection of Clinically Significant Prostate Cancer and Can Be Used as Reflex Tests

Abstract

Context.— There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.— To evaluate the clinical utility of [−2]pro–prostate-specific antigen ([−2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.— Two hundred thirty-seven men (PSA: 2–10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic (ROC) curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.— Both [−2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [−2]proPSA (%[−2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[−2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[−2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCa's. The same results could have been achieved by using [−2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[−2]proPSA and PHI, respectively). Conclusions.— The [−2]proPSA derivatives improve the diagnostic accuracy of csPCa, when the PSA value is between 2 and 10 ng/mL, allowing to spare unnecessary biopsies and to select patients for active surveillance. [−2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.