Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: Which is clinically effective and when?

Objectives. To ascertain when the serum determination of the free prostate- specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, an d whether the identification of PSA or prostate-specific membrane antigen ( PSM) mRNA in circulating cells has diagnostic advantages over the determina tion of their protein product. Methods. fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH), mR NA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identifie d in these samples by means of reverse transcriptase-polymerase chain react ion. Results. Overall, at a fixed specificity of 95%, the sensitivity of tPSA wa s 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BP H. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with sati sfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 3 8 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. Conclusions. The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utili ty of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no cl inical interest. UROLOGY 55: 710-715, 2000. (C) 2000, Elsevier Science Inc.