Introduction

Among men with localized high-risk prostate cancer (PCa), patients who met very-high-risk (VHR) criteria were shown to experience inferior outcomes after radical prostatectomy (RP) in a previous single institution study. Using a multi-institutional dataset, here we compared pathologic and oncologic outcomes between men with high-risk and VHR PCa who underwent RP between 2005-2015.

Methods

High-risk PCa was defined as biopsy Gleason pattern 8-10, PSA >20 ng/ml, or clinical stage T3-4. VHR PCa was defined according to pre-treatment criteria: primary Gleason pattern 5 on biopsy; or ? 5 cores containing Gleason sum 8-10; or multiple high-risk features. Pathologic outcomes by risk classification were compared using Chi-squared testing, and oncologic outcomes (biochemical recurrence - BCR, metastasis - METS, cancer specific mortality - CSM, and overall mortality - OM) were assessed using Cox proportional hazards models. Multivariable models included age, race, institution, and neoadjuvant androgen deprivation therapy as covariates.

Results

Among 1776 high-risk patients, 547 (30.8%) met VHR criteria. As compared to the high-risk cohort, VHR men had inferior pathologic outcomes. Positive margins: 38% vs 25%. Stage pT3b-4: 46% vs 17%. Stage pN1: 41% vs 15%. (P<0.001 for all comparisons). Over a median follow-up of 3 years, VHR PCa patients also had higher adjusted hazard ratios for BCR (2.32), METS (3.87), CSM (4.14), and OM (2.66). (P<0.001 for all comparisons).

Conclusions

In a multi-institutional experience of 1776 men who underwent treatment for high-risk PCa over a 10-year period, VHR cancer was strongly associated with adverse pathologic and oncologic outcomes as compared to high-risk disease. These findings serve to validate the prognostic significance of VHR PCa as a distinct entity from high-risk PCa, suggesting that VHR criteria should be considered during patient counseling and as a potential risk stratification tool in clinical trials.

Funding

none