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

Background: Multiple definitions of high-risk prostate cancer (PC) exist in clinical practice. Prior studies have primarily evaluated the variability in prediction of biochemical recurrence.

Objective: To examine the impact of different definitions on mortality after radical prostatectomy (RP).

Design, Setting, And Participants: 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.

Outcome Measurements And Statistical Analysis: Seven pretreatment definitions of high-risk PC (prostate-specific antigen [PSA] ≥20ng/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.

Results And Limitations: 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 ≥20ng/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 ≥20ng/ml to 19.97 for cT3; all p<0.001). All definitions of high risk except for preoperative PSA ≥20ng/ml were associated with a higher risk of OM (HR 1.72 for D'Amico to 3.31 for cT3; all p<0.01).

Conclusions: 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.

Patient Summary: 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.