Genomic Classifier Performance in Intermediate-Risk Prostate Cancer: Results From NRG Oncology/RTOG 0126 Randomized...

Area of Science:

• Oncology
• Genomics
• Prostate Cancer Research

Background:

• Intermediate-risk prostate cancer presents diverse treatment challenges.
• The 22-gene Decipher genomic classifier (GC) has shown promise in improving risk stratification.
• Validation in a randomized trial setting is crucial for clinical adoption.

Purpose of the Study:

• To assess the prognostic and predictive performance of the 22-gene GC in intermediate-risk prostate cancer patients.
• To validate the GC's ability to refine risk stratification in a real-world clinical trial setting.
• To evaluate the GC's impact on treatment decision-making.

Main Methods:

• Biopsy samples from 215 patients in the NRG Oncology/RTOG 01-26 phase 3 trial were analyzed.
• RNA was extracted to generate the 22-gene GC score.
• Multivariable Cox models were used to assess prognostic value for disease progression and individual endpoints.

Main Results:

• The 22-gene GC independently predicted disease progression (sHR=1.12), biochemical failure (sHR=1.22), distant metastasis (sHR=1.28), and prostate cancer-specific mortality (sHR=1.45).
• Ten-year distant metastasis rates were 4% for GC low-risk vs. 16% for GC high-risk patients.
• The GC demonstrated predictive value, showing differential treatment effects based on risk stratification (P-interaction=.04).

Conclusions:

• This study provides the first validation of a biopsy-based gene expression classifier in a randomized phase 3 trial for intermediate-risk prostate cancer.
• The 22-gene Decipher GC significantly improves risk stratification for patients with intermediate-risk disease.
• The Decipher GC can aid clinicians in making more informed treatment decisions.