Long-Term Impact of ADT in Favorable vs Unfavorable Intermediate-Risk Prostate Cancer

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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.

Study Details

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.

Key Findings

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

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