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

• Published in: Urology (Ridgewood, N.J.) N.J.), 2001-06, Vol.57 (6), p.1105-1111
• Main Authors: Miller, M.Craig, O’Dowd, Gerard J, Partin, Alan W, Veltri, Robert W
• Format: Article
• Language: English
• Subjects: Area Under Curve; Biological and medical sciences; Diagnosis, Differential; Humans; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Prostate-Specific Antigen - blood; Prostatic Hyperplasia - blood; Prostatic Hyperplasia - diagnosis; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Reference Values; Regression Analysis; Retrospective Studies; Sensitivity and Specificity; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(01)00953-0

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-1 system. To validate our calculated f/t 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 f/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 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 f/t PSA ratios had a Pearson’s correlation coefficient of 0.9130 in the retrospectively studied population of 362 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 (n = 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 f/t PSA ratio (greater than 25% cutoff) outperformed tPSA and yielded similar results in terms of biopsies spared and cancers missed. Conclusions. The calculated f/t PSA ratio and cPSA perform equally well in terms of the improvement of specificity in the discrimination of benign disease and CaP. The f/t 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.