Serum Prostate-Specific Antigen Testing for Early Detection of Prostate Cancer: Managing the Gap between Clinical and Laboratory Practice.

BACKGROUND: Current clinical practice guidelines (CPGs) for early detection of prostate cancer recommend for clinical decision-making a personalized prostate-specific antigen (PSA)-based management to improve the risk-benefit ratio of the screening strategy. Some important critical issues regarding the PSA determination in the clinical framework are, however, still neglected in current guidelines and a major focus of recommendations on those aspects would be needed to improve their effectiveness. CONTENT: Evidence sources in the available literature concerning the interchangeability of total PSA results measured with different commercial methods were critically appraised. We discuss how the heterogeneity of the measurand, the intermethod bias, and the design and selectivity of immunoassays may affect the diagnostic accuracy of selected PSA thresholds, and how knowledge of the analytical characteristics of assays in service, such as the recognized PSA circulating forms and the cross-reactivity with PSA homologs, is basic for improving both clinical decision-making in cancer screening and the reliability of the clinical interpretation of results at the individual level.
SUMMARY: Current CPGs ignore the poor interchangeability of PSA results obtained from different assays and the substantial role of laboratory issues in clinical performance of PSA testing. Involved stakeholders should contribute to fill the existing gap by: (a) preparing commutable reference materials for immunoassay calibration; (b) providing analytical characteristics that may explain the different performance of assays; (c) deriving outcome-based analytical performance specifications for PSA measurement; and (d) giving more focus on laboratory items when CPGs are prepared. © American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.