Prostate Cancer Gene 3 and Multiparametric Magnetic Resonance Can Reduce Unnecessary Biopsies: Decision Curve Analysis to Evaluate Predictive Models Reply

In the past, free PSA (fPSA) and the free/total PSA ratio (%fPSA) were introduced in an attempt to discriminate between benign prostatic hyperplasia and PC, in particular in those men with a total PSA (tPSA) value of 4-10 ng/mL. It is, nonetheless, important to underline that the use of fPSA and %fPSA has some limitations owing to fPSA instability, variable assay characteristics, and large prostate size (dilution effect).2 Stephan et al,3 analyzing the influence of prostate volume on the ratio of fPSA with tPSA in patients with PC and benign prostatic hyperplasia, concluded that %fPSA will yield significant results only in men with a normal prostate volume. A statistically significant difference (P <.01) will be found in the %fPSA value between patients affected by benign prostatic hyperplasia or PC only when the prostate volume is <40 cm3.3 In a recent multicenter study, conducted on a large cohort of 1026 patients (PROMEtheuS project), the investigators analyzed the ability of PSA to predict PC during biopsy. Considering PSA as a predictor of PC, the results were disappointing, with an AUC of tPSA, fPSA, and %fPSA of 0.549, 0.489, and 0.600, respectively.4