Variability of assay methods for total and free PSA after WHO standardization

Area of Science:

• Clinical Chemistry
• Biomarker Assay Standardization
• Prostate Cancer Diagnostics

Background:

• Variability in total PSA (tPSA) and free PSA (fPSA) commercial assays may be reduced by World Health Organization (WHO) calibration.
• Understanding this variability's impact on critical clinical cutoffs is essential.

Purpose of the Study:

• To evaluate the current variability of tPSA and fPSA commercial assays.
• To assess the impact of WHO calibration on assay performance.
• To determine if standardization has reduced inter-assay discrepancies in clinical practice.

Main Methods:

• Tested 167 samples (0-20 μg/L tPSA) using seven tPSA and six fPSA commercial assays.
• Utilized Access assay with both Hybritech and WHO calibrators for tPSA and fPSA.
• Performed Passing-Bablok analysis for PSA and percentage fPSA.

Main Results:

• Significant relative differences (>10%) in tPSA observed for ARCHITECT i2000, ADVIA Centaur XP, and WHO-calibrated Access at critical concentrations.
• IMMULITE 2000 assay exceeded the 10% relative difference limit for percent fPSA at critical concentrations (10%, 20%, 25%).
• Notable discordances between assays were found despite recent standardization efforts.

Conclusions:

• Significant discordances exist among commercial PSA assays, even after standardization.
• WHO calibration shows potential but does not fully resolve inter-assay variability.
• Further harmonization is crucial to achieve complete clinical concordance for PSA testing.