October 25, 2021—Chicago, Illinois—A meta-analysis has found that a genetic biomarker test accurately predicts recurrence and survival outcomes of high-risk prostate cancer. This outcome of a meta-analysis of pretreatment archival tissue from the randomized Radiation Therapy Oncology Group 9202, 9413, and 9902 trials was reported at the American Society for Radiation Oncology (ASTRO) Annual Meeting, from October 24 – 27.
Paul L. Nguyen, MD, of Harvard Medical School and Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, said in an ASTRO press release, "When a man is diagnosed with high-risk prostate cancer, we don't have a widely accepted way to subclassify their cancer and truly personalize their therapy, but we think we will in the near future."
Dr. Nguyen and colleagues used the Decipher biopsy test, which analyzes the activity of 22 genes in prostate tumors, to produce a score reflective of tumor aggressivity.
"We are optimistic that this score can tell us which men should have their treatment de-intensified, and which men should have their therapy intensified, meaning they will receive additional, second-generation hormone therapy," said Dr. Nguyen.
He added, "With this genetic marker, we hope to personalize therapy for men with high-risk prostate cancer rather than having a one-size-fits-all approach."
Decipher scores were calculated using RNA extracted from archival biopsy samples collected in the three major trials:
- N=90 Radiation Therapy Oncology Group 9202
- N=172 Radiation Therapy Oncology Group 9413
- N=123 Radiation Therapy Oncology Group 9902
They correlated Decipher scores with with long-term outcomes.
The genetic signature predicted which patients were more likely to:
- Develop distant metastases: hazard ratio 1.24, 95% confidence interval 1.11 - 1.39
- Die of their prostate cancer: azard ratio 1.27, 95% confidence interval 1.13 - 1.43
- Die of any cause: hazard ratio 1.12, 95% confidence interval 1.05 - 1.20)
The rate of distant cancer metastasis at 10 years was 29% when the score indicated more aggressive cancer vs 13% when the score signaled lower risk.
"This study was the first to validate a genetic biomarker for high-risk prostate cancer using pretreatment archival tissue from large, prospective, randomized trials," said Dr. Nguyen.
"Using archival tissue samples from a wide range of centers and patients—hundreds of cancer centers across the country—showed that this test can be helpful for many men with high-risk disease," he noted.
"A strength of using this tissue is that we have the complete follow-up for 20 to 30 years on these patients," said Dr. Nguyen.
Dr. Nguyen emphasized that the test needs further validation before it can become widely adopted. The results indicate that physicians may potentially use genetic test scores to personalize treatment for the most aggressive form of prostate cancer. To that end, he and A. Oliver Sartor, MD, of Tulane University, New Orleans, Louisiana, are leading the prospective, NRG-GU009/PREDICT-RT trial. The trial is evaluating Decipher's predictive validity in patients with high-risk prostate cancer.
"For a man with high-risk prostate cancer, this genetic score can be a very powerful prognostic tool that can tell us whether he is likely to be cured with treatment or to see his cancer return," said Dr. Nguyen. "I see this as a great opportunity to change the standard of care for patients by using genomics to personalize therapy."