Data from an ancillary analysis of the trial show the 22-gene classifier provides predictive evidence to guide treatment selection in intermediate-risk prostate cancer.
A retrospective ancillary analysis of the randomized phase III NRG/RTOG 0815 trial demonstrates that Veracyte’s Decipher Prostate Genomic Classifier can predict which intermediate-risk prostate cancer patients will benefit from adding short-term androgen deprivation therapy (ADT) to dose-escalated radiation.
The findings, presented at the 2026 American Society for Radiation Oncology Annual Meeting, provide Level 1B1 prognostic and predictive evidence for the test, expanding its clinical application from assessing disease progression risk to actively guiding therapy selection.
In the analysis, patients with higher Decipher scores experienced improved outcomes with the addition of short-term ADT to radiation. Conversely, patients with low Decipher scores derived minimal benefit from the addition of hormone therapy.
“For men with intermediate-risk prostate cancer, the question is not simply whether hormone therapy works—it is who truly needs it,” says Angela Jia, MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, in a release. “This analysis suggests tumor biology can distinguish patients who may achieve a substantial reduction in the risk of distant metastasis from those who may see little added benefit. That could help clinicians and patients make a more individualized decision about intensifying treatment.”
Refining Intermediate-Risk Stratification
While ADT can reduce the risk of cancer recurrence and distant spread, the treatment is associated with metabolic and quality-of-life complications. Because intermediate-risk prostate cancer is biologically heterogeneous, conventional clinical parameters such as Gleason grade, clinical stage, and prostate-specific antigen (PSA) levels often fail to identify which patients require intensified therapy.
The Decipher test refined patient prognosis independently of standard clinical variables. Higher genomic classifier scores were independently associated with an increased risk of biochemical failure, distant metastasis, and prostate-specific mortality.
“For men with intermediate-risk prostate cancer, these findings provide predictive evidence that treatment decisions can be guided by the biology of each patient’s tumor, not simply a broad clinical risk category,” says Daniel E Spratt, MD, chair of the department of radiation oncology at University Hospitals Cleveland Medical Center and professor at Case Western Reserve University School of Medicine, in a release. “Decipher may help identify who is likely to gain meaningful protection from metastasis by adding hormone therapy and who may face its health and quality-of-life effects with little added benefit. That is the kind of precision that patients and physicians need when deciding how aggressively to treat the cancer.”
NRG/RTOG 0815 Ancillary Analysis Details
The National Cancer Institute-approved ancillary study evaluated archived diagnostic biopsy specimens from 395 patients enrolled in NRG/RTOG 0815 using the locked, clinical-grade 22-gene Decipher Genomic Classifier. The biomarker cohort had a median follow-up of 10.2 years, remained balanced between treatment arms, and was representative of the trial’s overall 1,492-patient enrollment.
The primary endpoint of the study was distant metastasis, with secondary endpoints evaluating biochemical failure, metastasis-free survival, prostate cancer-specific mortality, and overall survival. The Decipher score was established as both prognostic for clinical outcomes and predictive of ADT benefit for distant metastasis and prostate cancer-specific mortality endpoints.
“These findings provide the first evidence that Decipher can predict which men with intermediate-risk prostate cancer are most likely to benefit from adding hormone therapy to radiation,” says Elai Davicioni, PhD, medical director of urology at Veracyte, in a release. “This extends the Decipher test’s prognostic use toward answering a more consequential question: Will this treatment make a meaningful difference for this patient? By revealing the biology beneath a broad clinical risk category, Decipher may help physicians intensify treatment for patients most likely to benefit while potentially sparing others from side effects with little added benefit.”
Further validation is underway in the prospective, biomarker-driven phase III NRG-GU010 (GUIDANCE) trial, which completed patient enrollment earlier this year to evaluate Decipher-guided treatment intensification and de-intensification strategies.
