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We applied a \u201ccumulative\/dynamic\u201d time-varying area under the curve (tAUC) for cumulative incidence of lethal prostate cancer (metastases\/cancer-specific death). In two prospective prostate cancer patient cohorts followed for lethal outcomes after radical prostatectomy, genitourinary pathologists undertook a histopathologic review of tumor specimens to assign Gleason grade groups 1-5, a known strong short-term prognostic factor. Among 1490 patients, 144 lethal events occurred during 35\u00a0years of follow-up (median, 18). The 10-year risk of lethal disease was 2% (95% CI, 1-3) for grade group 2 and 21% (95% CI, 16-28) for grade group 5 cancers. By 25\u00a0years, risks were 5% (95% CI, 3-8) and 32% (95% CI, 26-41), respectively. Prediction accuracy was strongest over the first 10\u00a0years (tAUC 0.83 [95% CI, 0.79-0.86]) but remained informative for 25\u00a0years (tAUC 0.76 [95% CI, 0.70-0.81]), including among long-term metastasis-free survivors. Risk-based AUCs instead of hazard-based \u201cincident\/dynamic\u201d AUCs allowed for interpretable characterization of prognostic accuracy over well-defined time periods. Lethal progression of high-grade prostate cancer occurred predominantly early, while that of lower grade tumors accumulated over decades after surgery.<\/jats:p>","DOI":"10.1093\/aje\/kwaf080","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T07:48:57Z","timestamp":1745567337000},"page":"919-926","source":"Crossref","is-referenced-by-count":0,"title":["Long-term performance of the Gleason score in predicting metastatic and fatal prostate cancer"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3549-9688","authenticated-orcid":false,"given":"Zhike","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. 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Chan School of Public Health , Boston, MA ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-8907","authenticated-orcid":false,"given":"Travis","family":"Gerke","sequence":"additional","affiliation":[{"name":"Prostate Cancer Clinical Trials Consortium , New York, NY ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-045X","authenticated-orcid":false,"given":"Andreas","family":"Pettersson","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-4563","authenticated-orcid":false,"given":"Richard","family":"Flavin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-792X","authenticated-orcid":false,"given":"Sinead","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA ,","place":["United States"]},{"name":"Department of Pathology, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7275-0597","authenticated-orcid":false,"given":"Philip W","family":"Kantoff","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY ,","place":["United States"]},{"name":"Convergent Therapeutics , Boston, MA ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-9067","authenticated-orcid":false,"given":"Tamara L","family":"Lotan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University , Baltimore, MD ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A","family":"Preston","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8628-5814","authenticated-orcid":false,"given":"Stephen P","family":"Finn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9674-8379","authenticated-orcid":false,"given":"Massimo","family":"Loda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Weill Cornell , New York, NY ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2815-3450","authenticated-orcid":false,"given":"Kathryn L","family":"Penney","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. 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