Impact of free prostate-specific antigen on discordant measurement results of assays for total prostate-specific antigen

Objectives, To determine why various assays for total PSA (t-PSA) produce discordant results in identical serum samples. Methods. A total of 84 sera from 40 patients with histologically confirmed benign prostatic hyperplasia and from 44 patients with untreated prostate cancer were analyzed with seven assays for t-PSA and the Hybritech research assay for free prostate-specific antigen (f-PSA). Comparison between assays was performed by linear regression of the t-PSA concentrations as well as between the t-PSA concentrations and the Wt-PSA ratios. Results. The coefficients of correlation for the investigated assays versus Hybritech Tandem-E range from 0.96 to 0.99. Nevertheless average PSA concentrations differed significantly from the Tandem-E assay in all assays. Despite a good correlation, some assays showed a regression line with a slope notably different from 1. In these assays, elevated concentrations were observed in sera with a high proportion of f-PSA. Conclusions. The study illustrates a significant and clinically relevant discordance between reported t-PSA concentrations for identical samples, depending on the assay used and on the contents of f-PSA in the sample. The interpretation of t-PSA concentrations requires awareness of the applied assay as well as the establishment of an assay-specific reference range in order to avoid inappropriate clinical consequences, such as unnecessary biopsies. Respective details must be contained in the laboratory reports. A change of assays without specifically reassessing previously valid reference ranges or the uncritical use of a customarily applied limit of <4 ng/mL will otherwise be harmful to the patient. Copyright 1996 by Elsevier Science Inc.