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

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.