Very high risk localized prostate cancer: definition and outcomes

PURPOSE: Outcomes in men with NCCN high-risk prostate cancer (PCa) can vary substantially--some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. MATERIALS AND METHODS: We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8–10, PSA >20 ng/ml, or clinical stage ≥T3). 28 alternate permutations of adverse grade, stage, and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. RESULTS: The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8–10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared to other high-risk men, VHR men were at significantly higher risk for metastasis (H.R. 2.75) and cancer-specific mortality (H.R. 3.44) (p <0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). CONCLUSIONS: Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncologic outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.