{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T08:30:37Z","timestamp":1794299437072,"version":"4.9.0"},"reference-count":57,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumour Biol."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate-specific antigen (PSA) remains the most widely used biomarker for prostate cancer screening, diagnosis, and monitoring. However, despite decades of standardization efforts, significant inter-assay variability persists, with important consequences for clinical interpretation and decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review aims to evaluate the impact of PSA calibration and harmonization on reference intervals, clinical thresholds, and population-based screening strategies in contemporary clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature-based analysis was conducted, examining studies on PSA assay standardization, analytical variability, and evidence from population screening trials, including considerations from a Health Technology Assessment perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The introduction of the World Health Organization (WHO) International Standard 96\/670 improved comparability among PSA assays, yet clinically relevant differences between platforms remain. This variability is driven by differences in calibration, antibody specificity, epitope recognition, and assay design. As a result, PSA values are not directly interchangeable across assays, and assay-specific cut-offs may be necessary to maintain diagnostic performance. Historically established thresholds, such as the 4\u00a0\u03bcg\/L cut-off and the \u201cgray zone,\u201d were derived using specific assay systems and are influenced by methodological limitations. PSA-derived metrics, including PSA density, improve specificity but are still affected by inter-assay variability. Evidence from large randomized trials supports a PSA cut-off of 3.0\u00a0\u03bcg\/L for population screening, showing a reduction in prostate cancer mortality when implemented within structured programs; however, this threshold is intrinsically linked to the analytical characteristics of the assays used. PSA also shows relevant intra-individual biological variability beyond analytical variation, with within-subject variation of 6\u201313%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PSA standardization remains incomplete, and inter-assay variability and biological variability continues to influence clinical interpretation. The implementation of PSA-based screening programs must explicitly consider the assay-specific nature of evidence-derived thresholds, including the 3.0\u00a0\u03bcg\/L cut-off, to ensure consistent, effective, and safe clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/14230380261466593","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:46:07Z","timestamp":1783921567000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Standardization of prostate-specific antigen assays: Impact on reference intervals and clinical decision thresholds"],"prefix":"10.1177","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5201-4162","authenticated-orcid":false,"given":"Xavier","family":"Filella","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics (CDB), Hospital Clinic,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2351"},{"key":"e_1_3_4_3_2","volume-title":"Proposal for a council recommendation on strengthening prevention through early detection: a new EU approach on cancer screening replacing council recommendation 2003\/878\/EC","author":"European Commission","year":"2022","unstructured":"European Commission. 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