Heterogeneity in Definitions of High-risk Prostate Cancer and Varying Impact on Mortality Rates after Radical Prostatectomy

Multiple definitions of high-risk prostate cancer (PC) exist in clinical practice. Prior studies have primarily evaluated the variability in prediction of biochemical recurrence. To examine the impact of different definitions on mortality after radical prostatectomy (RP). Retrospective study of 6477 men with clinically localized disease undergoing RP at Barnes-Jewish Hospital (St. Louis, MO, USA) and Cleveland Clinic (Cleveland, OH, USA) between 1995 and 2007. Seven pretreatment definitions of high-risk PC (prostate-specific antigen [PSA] ≥20 ng/ml, biopsy Gleason score 8–10, clinical stage ≥T2c, cT3, D’Amico definition, National Comprehensive Cancer Network definition, Kattan nomogram) were evaluated. The Kaplan-Meier method was used to generate unadjusted survival estimates. Multivariable Cox proportional hazard regression models (controlling for age) were used to estimate the hazard ratio (HR) for PC-specific mortality (PCSM) and overall mortality (OM) in the high-risk group compared to men with lower risk not meeting that definition. 6477 men were treated with RP from 1995 to 2007 and were followed for a median of 67 mo. Depending on the definition, patients with high-risk PC comprised between 0.7% (when using cT3 as the criterion) and 8.2% (when using the D’Amico criterion) of the population. The 10-yr PC survival estimates varied from 89.7% (PSA ≥20 ng/ml) to 69.7% (cT3) and overall survival ranged from 83.4% to 58.1%. On multivariable analysis, all high-risk definitions were associated with a higher risk of PCSM compared to lower risk (HR ranging from 4.38 for PSA ≥20 ng/ml to 19.97 for cT3; all p < 0.001). All definitions of high risk except for preoperative PSA ≥20 ng/ml were associated with a higher risk of OM (HR 1.72 for D’Amico to 3.31 for cT3; all p < 0.01). Heterogeneity in outcomes existed, depending on the pretreatment definition of high-risk PC. Clinical stage T3 and Gleason score 8–10 were most strongly associated with PCSM and OM. There is variability in prostate cancer outcomes after surgery, depending on the definition of pretreatment high-risk disease used. Clinical stage T3 and high Gleason score were most strongly associated with prostate cancer–specific mortality and overall mortality.