The authors of this study report the results of a phase 3 study comparing androgen deprivation therapy (ADT) alone with androgen deprivation therapy plus radiation therapy (RT) for locally advanced prostate cancer. There is uncertainty over whether adding RT improves overall survival in this area of practice and this study presents a planned interim analysis for when two-thirds of the events for the final analysis were recorded.

The unmasked, randomised study recruited patients (between 1995 to 2005) with locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25). Patients were randomly allocated (centrally by computer randomisation) to lifelong treatment with ADT only (n =602), or ADT and RT (n=603; 65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). Patients were stratified by institution, PSA concentration at diagnosis, type of ADT (orchiectomy or luteinising hormone-releasing hormone [LHRH] agonist), neoadjuvant ADT, lymph node staging, and Gleason score. The primary endpoint measure considered in the study was overall survival (defined as survival from time of randomisation to date of death from any cause or censored at the date of last follow-up). All efficacy analyses were conducted on an intention to treat and were based on data from all patients. Median follow-up was 6.0 years [IQR 4.4-8.0). The findings show:

• At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70-78 vs. 66%, 60-70; hazard ratio [HR] 0.77, 95% CI 0.61.0.98, p=0.033).

• Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0.5%) in the ADT only group, two (0.3%) in the ADT and RT group; diarrhoea grade >3, four patients (0.7%) vs eight (1.3%); urinary toxicity grade >3, 14 patients (2.3%) in both groups).

The authors conclude, “Our findings suggest that the benefits of the combination of ADT and RT should be discussed with all patients considering a curative treatment approach.”

The author of a related Comment article discusses the results of this study and writes, “Warde and colleagues have provided the strongest evidence to date that androgen deprivation therapy alone for men with high-risk prostate cancer is not adequate. These patients require an aggressive, multimodal approach incorporating prostate-directed local therapy. However, the crucial question—whether the optimum initial strategy should include radiation combined with androgen deprivation therapy, or surgery followed by selective radiation on the basis of pathological findings and early biochemical outcomes—is still open. The definitive answer will only come through trials of men with high-risk disease randomly assigned to receive surgery or radiation as an initial treatment.”