Study Type - Prognosis cohort series (multi-centre) Level of Evidence 4 What's known on the subject? and What does the study add? Men with high-risk prostate cancer experience recurrence, metastases and death at a higher rate in the prostate cancer population. This study adds greater than 20-year data regarding the continued evolution of high-risk prostate cancer toward high-Gleason disease as the sole determinant of high-risk status prior to radical prostatectomy. It validates the accumulation of multiple-risk factors as a poor prognostic indicator in a radical prostatectomy population and demonstrates long-term cancer specific outcomes, extending the findings demonstrated by previous publications. Objective: To investigate the outcomes and potential effect of improved longitudinal screening in men presenting with high-risk (advanced clinical stage [> T2b], Gleason score 8-10 or prostate-specific antigen [PSA] level > 20ng/mL) prostate cancer (PC). Patients and Methods: The Institutional Review Board approved, Institutional Radical Prostatectomy Database (1992-2010) was queried for men with high-risk PC based on D'Amico criteria. Year of surgery was divided into two cohorts: the Early PSA Era (EPE, 1992-2000) and the Contemporary PSA Era (CPE, 2001-2010). PC features and outcomes were evaluated using appropriate comparative tests. Results: In total, 667 men had high-risk PC in the EPE and 764 in the CPE. In the EPE, 598 (89.7%) men presented with one high-risk feature; 173 (29.0%) men had a Gleason score of 8-10 on biopsy. In the CPE, 717 (93.9%) men presented with one high-risk feature (P = 0.004) and 494 (68.9%) men had a Gleason score of 8-10. At 10 years, biochemical-free survival (BFS) was 44.1% and 36.4% in the EPE and CPE, respectively (P = 0.04); metastases-free survival (MFS) was 77.1% and 85.1% (P = 0.6); and PC-specific survival (CSS) was 83.3% and 96.2% (P = 0.5). BFS, MFS and CSS were worse for men with more than one high-risk feature in both eras. Conclusions: Over the PSA era, an increasing percentage of men with high-risk PC were categorized by a biopsy Gleason score of 8-10. The accumulation of multiple high-risk features increases the risk of biochemical recurrence, the development of metastases and death from PC. BFS, MFS and CSS are stable over the PSA era for these men. The balance between a greater proportion of men having high Gleason disease and a greater proportion with small, less advanced tumours may explain the stability in MFS and CSS over time.
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