As reported in the Journal of Clinical Oncology by Daniel J. Krauss, MD, and colleagues, the phase III NRG Oncology/RTOG 0815 study showed no significant improvement in overall survival with the addition of short-term androgen-deprivation therapy (ADT) to dose-escalated radiotherapy in patients with intermediate-risk prostate cancer. Benefits were observed in rates of metastases, prostate cancer–specific mortality, and prostate-specific antigen (PSA) failure.

Daniel J. Krauss, MD

Study Details

In the multicenter trial, 1,492 patients with stage T2b-T2c, Gleason score 7, or PSA > 10 and ≤ 20 ng/mL were randomly assigned between September 2009 and March 2016 to receive dose-escalated radiotherapy with (n = 742) or without short-term ADT (n = 750). Short-term ADT consisted of 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus an antiandrogen. Radiotherapy modalities used were either external-beam radiotherapy alone to 79.2 Gy or external-beam radiotherapy to 45 Gy with a brachytherapy boost. The primary endpoint was overall survival.

Overall Survival and Other Outcomes

Median follow-up among surviving patients was 6.4 years (range = 0.01–10.2 years) in the radiotherapy plus short-term ADT group vs 6.3 years (range = 0.0–10.3 years) in the radiotherapy group. Overall survival rates at 5 and 8 years in the radiotherapy plus short-term ADT group vs radiotherapy alone group were 91% vs 90% and 84% vs 79%, respectively (hazard ratio [HR] = 0.85, 95% CI = 0.65–1.11, P = .22).

Death from prostate cancer occurred in 1 patient in the radiotherapy plus short-term ADT group vs 10 in the radiotherapy alone group (HR = 0.10, P = .007). Cumulative incidence of distant metastasis at 5 and 8 years was 0.6% vs 3.1% and 1.0% vs 4.3% (HR = 0.25, P < .001). Local recurrence rates at 5 and 8 years were 0.6% vs 2.6% and 2.0% vs 3.9% (HR = 0.44, P = .021). PSA failure rates at 5 and 8 years were 8% vs 14% and 10% vs 21% (HR = 0.52, P < .001). Rates of receipt of salvage ADT at 5 and 8 years were 4.2% vs 6.1% and 5.8% vs 9.8% (HR = 0.62, P = .025). Combined rates of clinical or biochemical failure at 5 and 8 years were 7.9% vs 14.8% and 11.4% vs 22.5% (HR = 0.52, P = .001). No significant difference in non–prostate cancer mortality was observed (HR = 0.92, 95% CI = 0.70–1.21, P = .56).

Adverse Events

Adverse events of any grade occurred in 69% of the radiotherapy plus short-term ADT group vs 21% of the radiotherapy alone group (odds ratio [OR] = 8.70, P < .001); significant differences were observed in multiple domains, including endocrine symptoms (38% vs 0.5%), sexual/reproductive function (17% vs 3.4%), constitutional symptoms (29% vs 7.6%), gastrointestinal toxicity (21% vs 8.5%), and renal/genitourinary toxicity (44% vs 16%). Grade ≥ 3 acute adverse events occurred in 12% vs 2% of patients (OR = 5.67, P < .001). Acute grade ≥ 3 general cardiac events occurred in six patients vs one patient (P = .068). The cumulative incidence of late grade ≥ 3 adverse events was 15% vs 14% (P = .29).

The investigators concluded, “[Short-term ADT] did not improve overall survival rates for men with intermediate-risk prostate cancer treated with dose-escalated radiotherapy. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of [short-term ADT] on quality of life.”

Dr. Krauss, of Oakland University William Beaumont School of Medicine, Royal Oak, MI, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The trial was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.