Diagnostics company Veracyte announced today that data from a study of its Decipher Prostate Genomic Classifier, published today in the International Journal of Radiation Oncology, Biology, Physics has demonstrated it can improve risk stratification of patients with clinically high-risk prostate cancer. The data, the company said, is the first validation of a gene-expression biomarker using pre-treatment biopsy samples from prospective randomized clinical trials.
The intent of the Decipher test is to provide a more individualized approach to treating the roughly 30% of newly diagnosed men with prostate cancer that is classified as high risk. High-risk disease means there is an increased risk these patients will experience disease recurrence, metastasis, and death, compared with those men with low-risk disease. Unfortunately, knowing exactly how to treat each patient identified with high-risk disease is a challenge, as previously studies have shown that among this group, more than 70% who receive standard-of-care definitive radiotherapy and long-term androgen deprivation therapy (ADT) will not develop metastases.
“High-risk prostate cancer is heterogenous and standard prognostic tools do a poor job of discriminating which men are likely to develop distant metastases and may benefit from more aggressive therapy, and who will do well when treated with standard radiotherapy and ADT,” said Paul L. Nguyen, MD, vice-chair for Clinical Research in the Department of Radiation Oncology at The Dana Farber/Brigham Cancer Center and the study’s lead author.
“Because of this, clinicians are forced to use a one-size-fits-all approach that inherently leads to under- and over-treatment of many men. The data published today validate the role of the Decipher Prostate test in more accurately prognosticating patient outcomes, even within a high-risk group, to better personalize care.”
For this latest study, Nguyen, who is also a professor at Harvard Medical School, and his team used biopsy samples of 265 men with prostate cancer designated as high-risk by the National Comprehensive Cancer Network (NCCN) classification to derive risk scores. All of the samples came from patients who participated in one of three randomized Phase III trials conducted by NRG Oncology. With a median follow-up of 11 years, the researchers evaluated the association between Decipher scores and participants’ time to distant metastases (DM), prostate cancer-specific mortality (PCSM) and overall survival (OS).
Data showed that the Decipher Prostate was independently prognostic for DM, PCSM, and OS, with those identified as high risk by the tests experiencing worse outcomes than those who were classified as low-risk across all three endpoints. After adjusting for age, PSA, Gleason score, cT-stage, trial, and randomized treatment arm, the analysis found that the Decipher test scores were independently associated with DM (HR 1.22, 95%CI 1.09-1.36), PCSM (sHR 1.23, 95%CI 1.09-1.39), and OS (HR 1.12, 95%CI 1.05-1.20).
The team noted that the Decipher test showed similar prognostic results in patients receiving both short-term (four months) or long-term ADT, though those improved outcomes varied by risk. For example, at 10 years, the DM estimates were 31% for short-term vs 20% for long-term ADT in those with higher Decipher Prostate risk scores (an absolute benefit of 11%) but were 7% vs 4% in those with lower Decipher Prostate risk scores (an absolute benefit of 3%).
“This comprehensive analysis of three high-quality, randomized Phase III studies demonstrates that the Decipher Prostate Genomic Classifier provides information that can meaningfully impact clinical care for men with prostate cancer,” said Elai Davicioni, PhD, Veracyte’s medical director for Urology. “We believe the new data generated by Dr. Nguyen and colleagues could help physicians considering various treatment options for men with high-risk disease and who desire to tailor the duration and intensity of hormonal therapy for their patients on an individual basis.”
Hoping to build on these results, Decipher Prostate is now being researched in a prospective study called PREDICT-RT, which comprises two parallel randomized Phase III trials sponsored by the National Cancer Institute and conducted by NRG Oncology.