Discordant total and free prostate-specific antigen (PSA) assays: does calibration with WHO reference materials diminish the problem?

Prostate-specific antigen (PSA) assay-dependent variations could result in misinterpretation of individual PSA values. Therefore, the situation for clinical interpretation of PSA or percent free PSA (%fPSA) results is complicated. This review summarizes the differences in various total PSA (tPSA) and free PSA (fPSA) assays, and results obtained using the new World Health Organization (WHO) calibrated Access assays from various studies. Method comparisons between the traditionally calibrated Hybritech PSA and fPSA assays and the new "standardized" WHO calibrated assays yield results that are approximately 25% lower for PSA and fPSA. A PSA cut-off of 3 or 3.1 microg/L should be considered for WHO calibrated assays in order to achieve the same sensitivity/specificity profile as with a cut-off of 4 microg/L in traditionally calibrated assays. The %fPSA cut-offs could be retained.