Evaluation of the clinical performance of equimolar- and skewed-response total prostate-specific antigen assays versus complexed and free PSA assays and their ratios in discriminating between benign prostatic hyperplasia and prostate cancer

Abstract

Background: Prostate-specific antigen (PSA) exists in human serum in two principal forms, free PSA (fPSA) and protein-complexed PSA, predominantly PSA-ACT (α 1-antichymotrypsin). Equimolar response (EMR) total PSA (tPSA) immunoassays measure each of these forms equally while skewed-response (SKR) assays overestimate or underestimate the tPSA concentration. The advantages of EMR over SKR tPSA assays are controversial. Methods: We used five nonhuman serum-based samples each containing a different proportion of fSPA:PSA-ACT (0:100 to 100:0, %:%) and patients' serum samples from men with histologically confirmed benign prostatic hyperplasia (BPH) ( n=94) or PCA ( n=30) and a wide range of fPSA concentrations to investigate the molar response status of six tPSA assays. Receiver–operator characteristic (ROC) curve analysis was used to compare the discriminatory power of these assays in distinguishing men with BPH from those with PCA. Results: The Bayer Immuno-1 tPSA (BtPSA) assay demonstrated EMR characteristics and diagnostic accuracy similar to the Hybritech Tandem-E and Tandem-R tPSA assays. At 90% sensitivity, EMR tPSA assays had higher specificity than SKR tPSA assays. Conclusions: The BtPSA assay is an EMR tPSA assay and EMR assays provide improved diagnostic specificity over SKR tPSA assays.