June 15 2023
Results from the NRG Oncology NRG-RTOG 0232 clinical trial adding external beam radiotherapy (EBRT) to brachytherapy (BT) in men with intermediate-risk prostate cancer indicate that there was no improvement in freedom from progression (FFP) rates for patients. Late adverse events were significantly increased (> 6 months from treatment start) in genitourinary (GU)/gastrointestinal (GI) and analyzed as grade 2+ and as grade 3+ for patients on the trial who received the combination of EBRT and BT (COMBO arm) compared to patients who received BT alone (BT arm). These results, which were recently published in the Journal of Clinical Oncology, suggest that BT should remain the standard of care for this population.
“Many variations and intensifications of both EBRT and brachytherapy have been tested mainly in the higher and lower risk tiers of prostate cancer patients. Intermediate-risk prostate cancer patients represent a vast and heterogeneous grouping, which can make it difficult to find a specific therapy combination that appropriately treats their disease and the variety of risks that are possible within this population while avoiding added toxicity,” stated Jeff Michalski, MD, of the Washington University Siteman Cancer Center and the lead author of the NRG-RTOG 0232 manuscript.
NRG-RTOG 0232 randomly assigned588 men with intermediate-risk prostate cancer to either the COMBO or the BT treatment arm and 579 were eligible/analyzed. The COMBO arm consisted of 287 patients versus 292 on the BT arm. The primary objective of the trial was to determine whether the combination of EBRT and BT improved 5-year FFP using the ASTRO definition. Secondary objectives of the trial included FFP using the Phoenix definition, biochemical failure (per ASTRO and Phoenix), disease-specific mortality, local progression, distant metastases, survival, and toxicity.
There was not a significant improvement with the COMBO treatment for 5-year FFP rates by both ASTRO and Phoenix definitions. The 5-year FFP-ASTRO rate (95% CI) was 86% (81-90) on the COMBO arm versus 83% (78-87) with on the BT arm. The 5-year FFP-Phoenix rate was 88% (84-92) on the COMBO arm versus 86% (81-90) on the BT arm. There were no differences between treatment arms for acute GU and GI toxicities; however, 5-year cumulative incidence of late grade 2 or higher GU/GI toxicities was 43% (37-49) in the COMBO arm and 26% (21-31) in the BT arm (p<0.0001). 5-year cumulative incidence for late grade 3 or higher GU/GI toxicities was 8% (5-12) in the COMBO arm and 4% (2-6) in the BT arm (p=0.006). There were no grade 5 GU/GI toxicities.
“Although these results favor brachytherapy alone as a standard of care, it is important to note that more research is needed to explore local treatment options for selected intermediate-risk patients that safely improves outcomes,” added Dr. Michalski.
Further analysis is occurring for the quality-of-life secondary endpoint of the NRG-RTOG 0232 study. These data will be reported separately.
Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Operations), U24CA180803 (IROC), and U10CA180822 (SDMC) from the National Cancer Institute (NCI).
Michalski JM, Winter KA, Prestidge BR, Sanda MG, Amin M, Bice WS, Gay HA, Ibbott GS, Crook JM, Catton CN, Raben A, Bosch W, Beyer DC, Frank SJ, Papagikos MA, Rosenthal SA, Barthold HJ, Roach M 3rd, Moughan J, Sandler HM. Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial. J Clin Oncol. 2023 Jun 14:JCO2201856. doi: 10.1200/JCO.22.01856. Epub ahead of print. PMID: 37315297.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.