In an analysis of long-term data from NRG Oncology’s RTOG 9408 trial reported in JAMA Network Open, Zumsteg et al found that patients with favorable vs unfavorable intermediate-risk prostate cancer had improved overall survival, and that androgen-deprivation therapy (ADT) vs no ADT was associated with improved outcomes in unfavorable intermediate-risk—but not favorable intermediate-risk—patients.
RTOG 9408 was a randomized trial of radiotherapy with or without 4 months of ADT.
In this secondary analysis, 890 patients were categorized as having favorable intermediate-risk (n = 377) or unfavorable intermediate-risk (n = 513) on the basis of primary Gleason score, percentage of positive biopsy cores, and number of intermediate-risk factors.
Median follow-up was 17.8 years.
Compared with favorable intermediate-risk patients, unfavorable intermediate-risk patients had greater risks for distant metastasis (hazard ratio [HR] = 2.36, P = .001), prostate cancer–specific mortality (HR = 1.84, P = .001), and all-cause mortality (HR = 1.19, P = .03).
Among favorable intermediate-risk patients, use of ADT vs no ADT was not associated with improved risks for distant metastasis (HR = 1.55, P = .33), prostate cancer–specific mortality (HR = 0.63, P = .13), or all-cause mortality (HR = 1.02, P = .90). Among unfavorable intermediate-risk patients, ADT vs no ADT was associated with reduced risks for distant metastasis (HR = 0.48, P = .008) and prostate cancer–specific mortality (HR = 0.40, P < .001), but not all-cause mortality (HR = 0.84, P = .09).
The 15-year restricted mean survival time was prolonged with ADT vs no ADT among unfavorable intermediate-risk patients (10.5 vs 9.8 years, difference = 0.7 years, 95% confidence interval [CI] = 0.001–1.6 years, P = .0497). No significant prolongation with ADT vs no ADT was observed among favorable intermediate-risk patients (11.0 vs 10.7 years, difference = 0.3 years, 95% CI = −0.6–1.2 years, P = .50).
The investigators concluded, “To our knowledge, these results are the highest quality to date supporting a dichotomization of intermediate-risk prostate cancer into favorable and unfavorable subgroups, and support National Comprehensive Cancer Network recommendations to limit ADT use for patients with unfavorable intermediate-risk disease. Future studies exploring genomic classifiers to further personalize therapy in intermediate-risk prostate cancer should be performed.”
Zachary S. Zumsteg, MD, of the Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.