Contemporary use of complexed PSA and calculated percent free PSA for early detection of prostate cancer: Impact of changing disease demographics

Objectives. To assess the diagnostic performance of complexed prostate-spec ific antigen (cPSA), total PSA (tPSA), and calculated free/total PSA (f/t P SA) ratios in the differentiation of benign disease from prostate cancer (C aP) using a contemporary patient cohort. Methods. The cPSA, tPSA, and calculated fPSA values were determined using t he Bayer Immuno-I system. To validate our calculated fit PSA ratio, we also retrospectively measured fPSA using the Abbott AxSYM immunoassay system in archival pretreatment sera obtained between 1990 and 1997 from 362 men wit h clinically and biopsy-confirmed benign prostatic hyperplasia (n = 179) or CaP (n = 183). The diagnostic utility of tPSA, cPSA, and the calculated fi t PSA ratio was assessed using a contemporary test population consisting of sera prospectively collected between June 1999 and June 2000 from 3006 men who had recently undergone a systematic biopsy by urologists in clinical p ractices throughout the United States. This contemporary patient sample had biopsy diagnoses of either no evidence of malignancy (n = 1857) or CaP (n = 1149). All serum samples had tPSA values between 2.0 and 20.0 ng/mL. Results. The measured versus calculated fit PSA ratios had a Pearson's corr elation coefficient of 0.9130 in the retrospectively studied population of 352 men. The areas under the receiver operating characteristic curves (ROC- AUCs) for the measured and calculated f/t PSA ratios were indistinguishable (69.6% versus 69.2%, respectively). In the contemporary population In = 30 06), the ROC-AUC for tPSA, cPSA, and the calculated f/t PSA ratio was 52.2% , 53.9%, and 58.4%, respectively. We also compared the diagnostic performan ce using published cutoffs for tPSA (greater than 4.0 ng/mL), cPSA (greater than 3.8 ng/mL), and the f/t PSA ratio (greater than 15% and greater than 25%) in tPSA reflex ranges of 2 to 20 ng/mL and 2 to 10 ng/mL. We found tha t both cPSA and the Wt PSA ratio (greater than 25% cutoff) outperformed tPS A and yielded similar results in terms of biopsies spared and cancers misse d. Conclusions. The calculated Wt PSA ratio and cPSA perform equally well in t erms of the improvement of specificity in the discrimination of benign dise ase and CaP. The Wt PSA ratio and cPSA provide clinical benefits over the u se of tPSA alone, such as an increased sparing of unnecessary biopsies perf ormed with a manageable degree of risk of delayed cancer detection. UROLOGY 57: 1105-1111, 2001. (C) 2001, Elsevier Science Inc.