Very-high-risk localized prostate cancer: definition and outcomes

Area of Science:

• Oncology
• Urology
• Cancer Research

Background:

• Outcomes for men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) vary significantly.
• Current risk stratification tools do not adequately differentiate within the high-risk group.
• A need exists for a more precise definition of very-high-risk (VHR) PCa.

Purpose of the Study:

• To derive a binary definition for very-high-risk (VHR) localized PCa.
• To improve risk stratification at diagnosis for high-risk PCa patients.
• To aid in the selection of optimal therapies for distinct PCa subgroups.

Main Methods:

• Analysis of 753 men with NCCN high-risk PCa from the Johns Hopkins radical prostatectomy database.
• Evaluation of 28 permutations of grade, stage, and cancer volume for metastasis and mortality risk.
• Multivariable analyses to validate VHR criteria and assess their clinical relevance.

Main Results:

• The VHR cohort was defined by primary pattern 5, ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features.
• VHR criteria identified 15.1% of the high-risk PCa cohort.
• VHR men faced significantly higher risks of metastasis (HR 2.75) and cancer-specific mortality (HR 3.44) compared to other high-risk men.
• 10-year metastasis-free survival was 37% for VHR vs. 78% for other high-risk men; cancer-specific survival was 62% vs. 90%.

Conclusions:

• Men meeting VHR criteria represent a subgroup with exceptionally poor oncological outcomes within the NCCN high-risk classification.
• Distinguishing VHR localized PCa can enhance patient counseling.
• This definition may optimize the selection of candidates for multimodal treatments or clinical trials.