The free/total prostate-specific antigen ratio (%fPSA) is the best predictor of tumor involvement in the radical prostatectomy specimen among men with an elevated PSA

Background: The relationship between the free-to-total prostate-specific antigen ratio (%fPSA) and prostate cancer (CaP) pathology remains controversial. Previous reports have shown a direct correlation between %fPSA and prostate volume as well as an indirect correlation between %fPSA and unfavorable CaP pathology, particularly among men with an elevated PSA. We evaluated the use of %fPSA to predict CaP pathology including percent of tumor involvement in the radical prostatectomy (RP) specimen. Methods: We prospectively analyzed 124 consecutive patients with CaP who underwent RP. In all patients, preoperative frozen serum was analyzed for assessment of %fPSA (Abbott Axsym). Pathologic review was performed using whole mount sections and total tumor volume was determined by planimetry. Statistical comparison between %fPSA and pathology was performed using log transformation. Results: Percent fPSA was indirectly correlated with prostate volume in both the entire group (N=124) and among those patients (N=87) with a total PSA >4 ng/mL (P<0.001). Overall, both %fPSA and total PSA also correlated with total tumor volume (P=0.03 and P=0.01, respectively) and Gleason sum (P<0.001 and P<0.01). When we evaluated the percent of tumor involvement (tumor density) defined as the volume of tumor per gland divided by total gland volume, for the entire population, both total PSA and %fPSA were predictive with equal significance (P<0.001). However, among the subset of patients with a PSA>4.0 ng/mL, there was only a significant correlation between tumor density and %fPSA as compared to total PSA (P<0.001 vs. P=0.06, respectively). Conclusions: Independent of prostate volume, %fPSA is reflective of CaP pathology. Specifically, %fPSA was inversely correlated with tumor volume, Gleason sum and ECE. Among patients with modest PSA elevations, %fPSA was better than PSA in predicting percent of tumor involvement (tumor density) in the RP specimen.