Long-term performance of the Gleason score in predicting metastatic and fatal prostate cancer

The time-dependence in the performance of prognostic factors for cancer survivorship is typically incompletely understood, including in prostate cancer. We applied a "cumulative/dynamic" 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 1,490 patients, 144 lethal events occurred during 35 years 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 years, risks were 5% (95% CI 3, 8) and 32% (95% CI 26, 41), respectively. Prediction accuracy was strongest over the first 10 years (tAUC 0.83, 95% CI 0.79, 0.86) but remained informative for 25 years (tAUC 0.76, 95% CI 0.70, 0.81), including among long-term metastasis-free survivors. Risk-based AUCs instead of hazard-based "incident/dynamic" 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.

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Publication Details

Journal
American Journal of Epidemiology
Published
2025-04-25
DOI
https://doi.org/10.1093/aje/kwaf080
Primary Topic
Prostate Cancer Diagnosis and Treatment
Type
article
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article

Long-term performance of the Gleason score in predicting metastatic and fatal prostate cancer

Tamara L. Lotan, Stephen P. Finn, Richard Flavin, Michelangelo Fiorentino et al.
American Journal of Epidemiology
Prostate Cancer Diagnosis and Treatment
article

Long-term performance of the Gleason score in predicting metastatic and fatal prostate cancer

Tamara L. Lotan, Stephen P. Finn, Richard Flavin, Michelangelo Fiorentino, Jane B. Vaselkiv, Sinéad Flanagan, Lorelei Ann Mucci, Kathryn L. Penney, Konrad Hermann Stopsack, Philip W. Kantoff, Travis Gerke, Massimo F. Loda, Andreas Pettersson, Zhike Lin, Mark A. Preston
article en

Abstract

The time-dependence in the performance of prognostic factors for cancer survivorship is typically incompletely understood, including in prostate cancer. We applied a "cumulative/dynamic" 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 1,490 patients, 144 lethal events occurred during 35 years 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 years, risks were 5% (95% CI 3, 8) and 32% (95% CI 26, 41), respectively. Prediction accuracy was strongest over the first 10 years (tAUC 0.83, 95% CI 0.79, 0.86) but remained informative for 25 years (tAUC 0.76, 95% CI 0.70, 0.81), including among long-term metastasis-free survivors. Risk-based AUCs instead of hazard-based "incident/dynamic" 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.

American Journal of Epidemiology
Brigham and Women's Hospital (US), American Cancer Society (US), Memorial Sloan Kettering Cancer Center (US), Harvard University (US), Johns Hopkins University (US), Trinity College Dublin (IE), Cornell University (US), Johns Hopkins Medicine (US), Karolinska Institutet (SE), Massachusetts General Hospital (US), Prostate Cancer Research (GB), Convergent Science (United States) (US), Cancer Clinic (US), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 86%
Prostate Cancer Diagnosis and Treatment
DOISourceOpenAlex
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