Improving the Prediction of Pathologic Outcomes in Patients Undergoing Radical Prostatectomy: The Value of Prostate Cancer Antigen 3 (PCA3), Prostate Health Index (Phi) and Sarcosine

Background: Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over- treatment. To this aim, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been shown as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume institution. Materials and Methods: The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. Results: We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV) ≥0.5 ml, pathologic Gleason sum (GS) ≥7 and pT3 disease (all p-values ≤0.01). ROC curve analysis showed that phi is an accurate predictor of high stage (AUC 0.85 (0.77-0.93)), high grade (AUC 0.83 (0.73-0.93)) and high volume disease (AUC 0.94 (0.88-0.99)). Sarcosine showed a comparable AUC (0.85 (0.76-0.94)) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). Conclusion: PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Prostate-specific antigen (PSA) screening lead to an increasing number of men identified with low-stage and low-grade disease in the setting of prostate cancer (PCa). These subjects are good candidates for treatments other than radical prostatectomy (RP), such as active surveillance (AS) or focal therapy (1). The best treatment chosen should maximize oncologic and functional outcomes. Circulating and urinary biomarkers represent a promising approach to identify men with apparently low-risk biopsy pathology but who harbor potentially aggressive tumors unsuitable for active surveillance. Recent studies have shown that the Prostate Health Index (phi; (preoperative prostate-specific antigen isoform (p2PSA)/free PSA) x √ total PSA (tPSA)) improve the accuracy of tPSA and percentage of free PSA (%fPSA) in predicting the presence of PCa at prostate biopsy and it is also related to PCa aggressiveness at biopsy (2-7) and at RP (8, 9). Conflicting results have been reported for predicting the pathologic PCa characteristics of prostate cancer antigen 3 (PCA3) (9-11).