Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential

Area of Science:

• Uro-oncology
• Molecular pathology
• Prostate cancer research

Background:

• Gleason 3 + 3 = 6 prostate cancer is typically considered indolent.
• Accurate risk stratification is crucial for treatment decisions and active surveillance protocols.

Purpose of the Study:

• To determine the frequency of metastatic potential molecular characteristics in Gleason 3 + 3 = 6 prostate tumors.
• To assess the utility of the Decipher metastasis signature in this patient cohort.

Main Methods:

• Analysis of prostatectomy tissue from 337 patients with Gleason 3 + 3 disease.
• Independent pathological review using 2005 ISUP Gleason grading criteria.
• Calculation of the Decipher metastasis signature on each specimen.

Main Results:

• 80% of Gleason 3 + 3 tumors had low Decipher scores; 20% had intermediate or high scores.
• Higher Decipher scores correlated significantly with adverse pathological features (p < 0.001).
• Patients with pT3 disease or positive margins had higher median Decipher scores (0.30) vs. pT2 disease (0.23).

Conclusions:

• A notable proportion of Gleason 6 tumors possess molecular features associated with aggressive disease.
• Molecular profiling at diagnosis could improve patient selection for active surveillance and guide timely intervention.
• This highlights the importance of integrating molecular data with traditional pathology for enhanced prostate cancer management.