{"entity":{"id":"paper-catalona-psa-screening-test-nejm-1991","kind":"paper","name":"Measurement of prostate-specific antigen in serum as a screening test for prostate cancer","aka":["Catalona 1991","PSA screening 1991","PSA 4.0 threshold"],"tldr":"This is where the number 4.0 came from. Screening 1,653 healthy men over 50 with a blood test and biopsying those above that level found cancers that a finger examination would have missed, and the threshold entered practice worldwide.","summary":"William Catalona and colleagues measured serum prostate-specific antigen in 1,653 healthy men aged 50 or over, sent those at or above 4.0 micrograms per litre for rectal examination and ultrasonography, and biopsied those with abnormal findings. They compared the results against 300 men biopsied because of symptoms or an abnormal examination.\n\nThe paper is short, clear and enormously consequential. It established the 4.0 threshold, showed that the blood test detected cancers that digital rectal examination alone would have missed, and concluded that the combination of the antigen and examination detected prostate cancer better than examination alone. Within a decade prostate-specific antigen testing had spread through United States primary care without a randomised trial of whether it saved lives, which is why the two trials that followed, ERSPC and PLCO, matter so much and why they disagreed so badly.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1991","url":"https://doi.org/10.1056/nejm199104253241702"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1707140/"}],"tags":["prostate-evidence"],"related":["paper-stamey-psa-serum-marker-nejm-1987","paper-schroder-erspc-screening-mortality-nejm-2009","paper-andriole-plco-prostate-screening-nejm-2009","early-detection-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","number-needed-to-screen","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1991,"doi":"10.1056/nejm199104253241702","pmid":"1707140","authors":"Catalona WJ, Smith DS, Ratliff TL, et al.","paperType":"observational","findings":["Serum prostate-specific antigen was 4.0 to 9.9 micrograms per litre in 107 of the 1,653 men (6.5 percent); of the 85 in that group who had biopsies, 19 (22 percent) had prostate cancer.","Levels were 10.0 micrograms per litre or higher in 30 men (1.8 percent); of the 27 in that group who had biopsies, 18 (67 percent) had cancer.","Rectal examination alone would have missed 12 of the 37 cancers (32 percent); ultrasonography alone would have missed 16 of 37 (43 percent).","Prostate-specific antigen measurement had the lowest error rate of the individual tests, and antigen measurement plus rectal examination the lowest of the two-test combinations.","The authors concluded that antigen measurement plus rectal examination, with ultrasonography in men with abnormal findings, detects prostate cancer better than rectal examination alone."],"whatItMeans":"The paper that made opportunistic prostate-specific antigen testing routine, and the source of the threshold still printed on laboratory reports. Everything in the overdiagnosis literature is, in effect, an audit of what this recommendation did when it was applied to whole populations.","caveats":["A detection study: it measured how many cancers were found, not how many deaths were prevented, and the mortality question needed randomised trials.","The 4.0 micrograms per litre threshold is a convention from this cohort, not a biological boundary; cancer occurs below it and benign enlargement raises it.","1,653 self-selected volunteers aged 50 or over at one United States centre; the yield in other populations differs."],"changedPractice":true,"participants":1653},"route":"/key-papers/paper-catalona-psa-screening-test-nejm-1991/","neighbours":{"paper":[{"id":"paper-damico-risk-groups-jama-1998","kind":"paper","name":"D'Amico risk groups: biochemical outcome after radical prostatectomy, external beam radiotherapy or brachytherapy","route":"/key-papers/paper-damico-risk-groups-jama-1998/"},{"id":"paper-schroder-erspc-screening-mortality-nejm-2009","kind":"paper","name":"ERSPC: screening and prostate cancer mortality in a randomised European study","route":"/key-papers/paper-schroder-erspc-screening-mortality-nejm-2009/"},{"id":"paper-andriole-plco-prostate-screening-nejm-2009","kind":"paper","name":"PLCO: mortality results from a randomised prostate cancer screening trial","route":"/key-papers/paper-andriole-plco-prostate-screening-nejm-2009/"},{"id":"paper-stamey-psa-serum-marker-nejm-1987","kind":"paper","name":"Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate","route":"/key-papers/paper-stamey-psa-serum-marker-nejm-1987/"}],"roadmap":[{"id":"early-detection-roadmap","kind":"roadmap","name":"Early detection roadmap: organ screening → blood tests for many cancers","route":"/roadmaps/early-detection-roadmap/"},{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"cancer":[{"id":"prostate-intermediate-risk","kind":"cancer","name":"Localised prostate cancer, intermediate risk","route":"/cancers/prostate-intermediate-risk/"},{"id":"prostate-low-risk","kind":"cancer","name":"Localised prostate cancer, very low and low risk","route":"/cancers/prostate-low-risk/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"term":[{"id":"lead-time-bias","kind":"term","name":"Lead time, and lead-time bias","route":"/terms/lead-time-bias/"},{"id":"number-needed-to-screen","kind":"term","name":"Number needed to screen (and number needed to diagnose)","route":"/terms/number-needed-to-screen/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"screening","kind":"term","name":"Screening","route":"/terms/screening/"}],"bottleneck":[{"id":"b-overdiagnosis","kind":"bottleneck","name":"Overdiagnosis and false alarms","route":"/bottlenecks/b-overdiagnosis/"},{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}