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-specific antigen (cPSA), total PSA (tPSA), and calculated free/total PSA (f/t PSA) ratios in the differentiation of benign disease from prostate cancer (CaP) using a contemporary patient cohort. Methods. The cPSA, tPSA, and calculated fPSA values were determined using the 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 with clinically and biopsy-confirmed benign prostatic hyperplasia (n = 179) or CaP (n = 183). The diagnostic utility of tPSA, cPSA, and the calculated fit 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 practices 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 correlation 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 = 3006), 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 performance 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 that both cPSA and the Wt PSA ratio (greater than 25% cutoff) outperformed tPSA and yielded similar results in terms of biopsies spared and cancers missed. Conclusions. The calculated Wt PSA ratio and cPSA perform equally well in terms of the improvement of specificity in the discrimination of benign disease and CaP. The Wt PSA ratio and cPSA provide clinical benefits over the use of tPSA alone, such as an increased sparing of unnecessary biopsies performed with a manageable degree of risk of delayed cancer detection. UROLOGY 57: 1105-1111, 2001. (C) 2001, Elsevier Science Inc.