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The use of androgen-deprivation therapy (ADT) as an adjunct to radiotherapy (RT) has been shown to improve disease-free and overall survival in men with high-risk localized prostate cancer or locally advanced disease. To determine whether this therapy also has survival benefits in patients with earlier-stage disease, researchers conducted a phase III trial, involving 1979 men with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and prostate-specific antigen (PSA) levels ≤20. The median age of participants was 71; 35% had low-risk disease, 54% had intermediate-risk disease, and 11% had high-risk disease.
Patients were randomized to undergo external beam RT (total dose, 66.6 Gy) with or without 4 months of ADT. During a median follow-up of approximately 9 years, the combined-therapy group had significantly better 10-year outcomes than the RT-alone group, including a higher rate of overall survival (62% vs. 57%; P=0.03), a lower rate of prostate cancer–specific mortality (4% vs. 8%; P=0.001), and a lower rate of biochemical failure (26% vs. 41%; P<0.001).
In an unplanned subgroup analysis, the mortality benefits of combined therapy were limited to men with intermediate-risk disease. Overall, radiation-induced adverse effects, both acute and late, were similar between the treatment groups.
Jones CU et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011 Jul 14; 365:107.
D'Amico AV. Risk-based management of prostate cancer. N Engl J Med 2011 Jul 14; 365:169.
Comment
Although the subgroup analysis was not prespecified, it provides good evidence that adding ADT to external beam RT is not beneficial in men with low-risk disease. An editorialist states that, on the basis of these data and emerging evidence of potentially significant toxicity with ADT, one can reasonably conclude that hormonal therapy is not indicated for low-risk patients. The editorialist and the study authors note that, for high-risk patients, the duration of ADT used was probably not sufficient to see the expected benefit. For intermediate-risk patients, adding ADT to RT improved survival, but is the hormonal therapy necessary now that patients can safely receive higher doses of radiation? This question is currently being addressed in the RTOG 0815 trial, which compares dose-escalated RT alone to dose-escalated RT plus 6 months of ADT in intermediate-risk patients.