Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial

PURPOSE: Complexed (c) prostate specific antigen (PSA) has been shown to enhance specificity for prostate cancer (CaP) detection over total PSA (tPSA), although a large multi-institutional prospective evaluation was required to confirm these findings. We compared the clinical performance of cPSA with tPSA as a first line test for CaP detection and secondarily to determine if PSA ratios, namely percent free PSA (fPSA) and percent cPSA, can provide further enhancement in diagnostic performance over cPSA or tPSA. MATERIALS AND METHODS: Consecutive men scheduled for initial biopsy of the prostate were enrolled prospectively at each of 7 university centers and community based urology practices. Serum was collected and tested with the Immuno 1 (Bayer Diagnostics, Tarrytown, New York), tPSA and cPSA, and Access (Beckman, Inc., San Diego, California) fPSA and tPSA methods. RESULTS: A total of 831 patients were evaluated, of whom 313 (37.5%) were diagnosed with CaP. ROC curve analysis performed from the results of all samples and those within the clinically relevant cPSA ranges of 1.5 to 3.2, 1.5 to 5.1, 1.5 to 8.3 and 3.2 to 8.3 ng/ml (tPSA 2 to 4, 2 to 6, 2 to 10 and 4 to 10 ng/ml, respectively) indicated a significant improvement in the AUC ROC curve for cPSA compared with tPSA (p < or =0.001). Using cutoff points that provide a sensitivity of 80% to 95% for CaP detection within the 1.5 to 8.3 ng/ml cPSA range cPSA provided a statistically significant enhancement in specificity over tPSA of 6.2% to 7.9%. Within the cPSA range of 1.5 to 3.2 ng/ml using a cutoff point of 2.5 ng/ml for tPSA and 2.2 ng/ml for cPSA provided a specificity of 21.2% and 35%, respectively, and 85% sensitivity for CaP detection. PSA ratios provided no further enhancement in specificity over cPSA within these ranges. CONCLUSIONS: The use of cPSA as a single test provided improved specificity over tPSA. Percent fPSA and percent cPSA offered little to no additional benefit in the differentiation of benign and malignant disease at clinically relevant cPSA concentrations.