Evolution of the clinical presentation of men undergoing radical prostatectomy for high-risk prostate cancer


Phillip M. Pierorazio, Johns Hopkins University – Urology, 600 N Wolfe Street, Baltimore, MD 21287, USA. e-mail: philpierorazio@jhmi.edu


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.


  • • 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 >20 ng/mL) prostate cancer (PC).


  • • 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.


  • • 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.


  • • 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.