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 ∼25% lower for PSA and fPSA. A PSA cut-off of 3 or 3.1 μg/L should be considered for WHO calibrated assays in order to achieve the same sensitivity/specificity profile as with a cut-off of 4 μg/L in traditionally calibrated assays. The %fPSA cut-offs could be retained.
Background: The metrological traceability of prostate-specific antigen (PSA) assay calibration to WHO standards is desirable to potentially improve the comparability between PSA assays. A method comparison was performed between the traditionally standardized Beckman Coulter Hybritech Access PSA and free PSA (fPSA) assays and a new alternate calibration of assays aligned to the WHO standards 96/670 and 96/668, respectively.
Methods: Sera from 641 men with and without prostate cancer, various control materials and mixtures of different proportions of the WHO standards were measured with both assay calibrations.
Results: Excellent comparability between the corresponding assay calibrations was observed, with correlation coefficients of at least 0.996. The Passing-Bablok slopes were 0.747 for total PSA (tPSA), 0.776 for fPSA and 1.02 for the percentage ratio of fPSA to tPSA (%fPSA), while the corresponding percentages of the new WHO-aligned assay results related to the traditional assays were 76.2%, 77% and 102.2%. Receiver operating characteristics revealed no differences between the two PSA assay calibrations.
Conclusions: The WHO calibration yields results approximately 25% lower for tPSA and fPSA values when compared with the conventional Hybritech calibration. Using the WHO-aligned PSA assay, a tPSA cut-off of 3 μg/L should be considered in clinical practice, while %fPSA cut-offs could be retained.