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.
We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.
Background Previous studies have shown that the harmonization of prostate-specific antigen (PSA) assays remained limited even after the introduction of WHO International Standards. This information needs updating for current measuring systems (MS) and reevaluation according to established analytical performance specifications (APS) and the characteristics of antibodies used. Methods Total (tPSA) and free (fPSA) PSA were measured in 135 and 137 native serum samples, respectively, by Abbott Alinity i, Beckman Access Dxl, Roche Cobas e801, and Siemens Atellica IM MSs. Passing–Bablok regression and difference plots were used to compare results from each MS to the all-method median values. Agreement among methods was evaluated against APS for bias derived from biological variation of the 2 measurands. Results The median interassay CV for tPSA MSs (11.5%; 25–75th percentiles, 9.2–13.4) fulfilled the minimum APS goal for intermethod bias (15.9%), while the interassay CV for fPSA did not [20.4% (25–75th percentiles, 18.4–22.7) vs goal 17.6%]. Considering the all-method median value of each sample as reference, all tPSA MSs exhibited a mean percentage bias within the minimum goal. On the other hand, Alinity (+21.3%) and Access (−24.2%) were out of the minimum bias goal for fPSA, the disagreement explained only in minimal part by the heterogeneity of employed antibodies. Conclusions The harmonization among tPSA MSs is acceptable only when minimum APS are applied and necessitates further improvement. The marked disagreement among fPSA MSs questions the use of fPSA as a second-level test for biopsy referral.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.