September 16 2025
September is Prostate Cancer Awareness Month, and the theme of this year’s campaign is “awareness needs action.” NRG Oncology has fueled that action by accruing to multiple active studies in the prostate cancer space. These trials include varying objectives to assess everything from tailoring treatment based on the patient, shorten the duration of treatment, and different treatment approaches towards tackling multiple types of prostate cancers. Below, we provide an overview of each trial available through NRG Oncology (NRG-GU008, NRG-GU010, NRG-GU011, and NRG-GU013):
“INNOVATE” - INtensifying treatment for NOde positive prostate cancer by VArying the hormonal ThErapy (NRG-GU008): Randomized Phase III Trial Incorporating Apalutamide and Advanced Imaging into Salvage Treatment for Patients with Node-Positive Prostate Cancer After Radical Prostatectomy
The INNOVATE (NRG-GU008) trial is examining whether the addition of the hormone therapy drug apalutamide to the current standard of care improves metastasis-free survival (MFS) in patients with node-positive prostate cancer who have detectable prostate-specific antigens (PSAs) following a radical prostatectomy. The trial is now actively accruing patients in this population. Eligible patients are those who have had a radical prostatectomy and have a detectable (any non-zero) PSA after surgery, and are node-positive either on surgical pathology and/or have nodal recurrence on imaging. Patients will be randomly assigned to receive either salvage radiotherapy and a GnRH agonist/antagonist (the current standard of care) or to receive radiotherapy and a GnRH agonist/antagonist plus apalutamide (a more aggressive treatment).
“In prostate cancer research and treatment, the emphasis is shifting away from patients with early, low-risk disease. Node-positive patients represent those at the other end of the spectrum who are clearly among the most likely to benefit from a large-scale randomized trial, and specifically from exploring more aggressive treatment options. And yet, given the lack of clinical trial data, the optimal treatment for this subset of patients remains unknown, and there are currently no active trials seeking to fill this knowledge gap. NRG-GU008, building on the promise of recent trials, will examine the addition of apalutamide to the current treatment regimen with the goal of redefining—or rather, more accurately, defining—the standard of care for prostate patients with node-positive disease,” stated Ronald Chen, MD, MPH, of the University of Kansas Medical Center, the Principal Investigator of the NRG-GU008 trial.
“GUIDANCE” - Parallel Phase III Randomized Trials Of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification And Intensification Clinical Trial Evaluation (NRG-GU010)
The GUIDANCE (NRG-GU010) trial is examining, in patients with unfavorable intermediate risk prostate cancer, both whether patients with a lower Decipher genomic risk score could be treated as effectively with a less intensive treatment than the current standard of careand whether patients with a higher Decipher genomic risk score would have improved metastasis-free survival with a more intensive treatment than the current standard of care. Patients will undergo the Decipher genomic risk test and then be stratified based on whether they have high or low genomic risk. Patients with low genomic risk will be randomized to receive either the standard of care (radiotherapy plus six months of ADT) or radiotherapy alone. Patients with high genomic risk will be randomized to receive either the standard of care or the standard of care plus 6 months of the hormone therapy drug darolutamide. The intensification cohort of this study met accrual and is now closed. The trial’s de-intensification cohort is still currently accruing.
“Recently there has been recognition that patients with intermediate risk prostate cancer have markedly different outcomes when treated with the current standard of care, particularly when adding androgen deprivation therapy to radiotherapy. Although these patients have been stratified using traditional clinicopathologic criteria, treatment could very likely be optimized by further stratifying based on each patient’s tumor genome. NRG-GU010 will therefore use the genomic Decipher assay, which has been validated to predict for patients with better and worse prognoses, to stratify patients into higher- and lower-risk populations and assess whether lower-risk patients could be given less aggressive treatment with equal efficacy while avoiding significant adverse effects and higher-risk patients could be given more aggressive treatment to improve metastasis-free survival. In particular, de-intensification in lower-risk patients could spare hundreds of thousands of men worldwide from developing significant ADT-related side effects,” stated Neil Desai, MD, MHS, of the University of Texas Southwestern Medical Center and Alejandro Berlin, MD, MSc, of the Princess Margaret Cancer Centre University Health Network, the Co-Principal Investigators of the NRG-GU010 trial.
“PROMETHEAN” - A Phase II Double-Blinded, Placebo Controlled Trial of Prostate Oligometastatic Radiotherapy with or without Androgen Deprivation Therapy in Oligometastatic Prostate Cancer (NRG-GU011)
The PROMETHEAN (NRG-GU011) trial is examining whether the addition of hormone therapy to radiotherapy will reduce the development of new metastases in patients who have previously been treated for prostate cancer with either surgery or radiation and now have oligometastatic disease as detected by a PET scan. The study is actively accruing patients in this population. Patients on the study will be randomized to receive either radiotherapy plus a placebo or radiotherapy plus androgen deprivation therapy (ADT) in the form of the hormonal therapy drug relugolix.
“Because patients with prostate cancer who are diagnosed with PET-detected oligometastatic disease comprise a new patient population, there is much value in a study evaluating the benefits and detriments of combination therapy in this subset of patients. NRG-GU011, building on studies of prostate cancer at an earlier stage which showed that combining radiation and hormonal therapy has improved outcomes over either therapy alone, is seeking to determine whether the same holds true for patients with oligometastatic prostate cancer. NRG-GU011 will provide critical information on treatment efficacy and toxicity in order to educate patients with oligometastatic prostate cancer better on how to optimize their treatment outcomes while minimizing the impact on quality of life,” stated Bridget Koontz, MD, of AdventHealth, the Principal Investigator of the NRG-GU011 trial.
The Phase III “High-Five Trial” (NRG-GU013): Five Fraction Radiation For High-Risk Prostate Cancer
The Phase III “High-Five Trial” (NRG-GU013) is examining whether a shorter course of radiation at a higher dose (delivered in 5 treatments over 2 weeks) is equally as effective in preventing the recurrence of cancer in patients with high-risk prostate cancer as the standard course of radiation, which is delivered at a lower dose over a longer timeframe (20 to 45 treatments over 4 to 9 weeks). The trial is now actively accruing patients in this population. Patients will be randomized to receive either conventional or moderate hypofractionation (the standard of care) or ultrahypofractionation (SBRT).
“There is great societal and patient interest in reducing the duration of radiation for high-risk prostate cancer. However, there are no randomized trials comparing a five-fraction ultrahypofractionation approach to moderate or conventional hypofractionation for men with high-risk prostate cancer. NRG-GU013, if it establishes the efficacy and safety of a shorter-duration, five treatment ultrahypofractionation (SBRT) regimen, could improve the quality of life of prostate cancer patients by establishing a more convenient and less burdensome treatment as the standard of care,” stated Karen Hoffman, MD, of the University of Texas MD Anderson Cancer Center and Paul Nguyen, MD, of the Dana-Farber Cancer Institute, the Co-Principal Investigators of the NRG-GU013 trial.