Preoperative prostate-specific antigen isoform p2PSA ≤ 22.5 pg/ml predicts advanced prostate cancer in patients undergoing radical prostatectomy

Background: The prediction value of prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA) for detecting advanced prostate cancer (PCa) remains unclear. Our objective was to evaluate the additional clinical utility of p2PSA compared with total PSA (tPSA), free PSA (fPSA), and preoperative Gleason score (Gls) in predicting locally advanced PCa (pT3/T4) with high-accuracy discrimination. The aim was to develop a novel classification based on p2PSA and preoperative Gls for predicting advanced PCa.

Materials and methods: In 208 consecutive men diagnosed with clinically localized PCa who underwent radical prostatectomy, we determined the predictive and discriminatory accuracy of serum tPSA, fPSA, percentage of fPSA to tPSA, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and the Prostate Health Index. The cutoff level of p2PSA with best accuracy was estimated. The novel classification was developed by analyzing the interaction between p2PSA and Gls in predicting pathologic outcomes using a chi-square automatic interaction detection analysis. Decision curve analysis was applied to test the clinical consequences of using the novel classification.

Results: On univariate analyses, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and Prostate Health Index were accurate but were not independent predictors by multivariate analysis. The p2PSA cutoff level of 22.5 pg/ml showed the best accuracy level for predicting and discriminating advanced diseases (area under the curve [AUC] = 0.725, sensitivity = 51.4%, specificity = 81.8%). By chi-square automatic interaction detection, univariate and multivariate analysis, a p2PSA level > 22.5 pg/ml was significantly associated with an increased frequency and risk of advanced disease. In patients with a p2PSA level ≤ 22.5 pg/ml, 91.8% of Gleason sum 6 PCa was organ confined. The combination of p2PSA and Gls enhanced slightly but significantly the predictive and discriminatory accuracy for advanced disease (0.6%-3.6%).

Conclusions: The p2PSA cutoff level of 22.5 pg/ml can accurately discriminate between organ-confined and advanced PCa. The additional use of p2PSA enhanced slightly the predictive accuracy for advanced PCa (pT3/pT4) and has limited additional predictive value in identifying aggressive PCa (Gls > 7a).