Serum (-5, -7) proPSA for Distinguishing Stage and Grade of Prostate Cancer

Background: ProPSA has been suggested for the detection of preferentially aggressive prostate cancer (PCa). We report on the use of proPSA and free PSA to enhance preoperative staging and grading. Patients and Methods: Serum samples from 376 PCa patients within the PSA range 1-25 Ig/l who underwent radical prostatectomy were analysed for PSA, free PSA (fPSA) and (-5, -7) proPSA. Results: ProPSA was only significantly different between pT2 and pT3 PCa (p=0.02) in the subgroup of patients with %fPSA<10%. The ratio proPSA/%fPSA differed between G2 and G3 (p=0.004), Gleason <7 and Gleason ≥7 (p=0.001), and pT2 and pT3 tumors (p<0.0001) at PSA 1-25 Ig/l. However, %fPSA improved differentiation only between Gleason <7 and Gleason ≥7 tumors, not between pT2 and pT3 or G2 and G3 tumors. Conclusion: ProPSA as a single parameter did not improve the detection of non-organ confined or aggressive PCa whereas proPSA/%fPSA further improved staging and grading within all analysed PSA ranges. Low diagnostic specificity is a major drawback of the marker prostate specific antigen (PSA) (1). The use of molecular forms of PSA such as free PSA and its ratio to total PSA (f/tPSA or %fPSA) have been proposed to enhance the specificity for the detection of prostate cancer (PCa) (2). Recently, serum free PSA was found to be a mixture of different subforms including proPSA, a precursor form of PSA, "benign" PSA (BPSA), a cleaved form of PSA (cleavages at Lys145 and Lys182), and "intact" (iPSA) an inactive form of free PSA (3).