This phase 3 clinical trial evaluated whether the addition of short-term ADT to radiotherapy improved outcomes in patients who had early, localized prostate cancer and a PSA level of 20 ng per milliliter or less — the subgroup of patients with prostate cancer who were known to have the most favorable prognosis at the time the study was initiated. Because of the indolent nature of the disease, a median follow-up period of more than 9 years for surviving patients and vigilant PSA monitoring were required to obtain meaningful results in a patient cohort in which most deaths were due to other causes.

The study showed that the addition of shortterm ADT to radiotherapy conferred a modest but significant increase in the 10-year rate of overall survival, from 57 to 62%. This increase was accompanied by a significant reduction in 10-year disease-specific mortality from 8% to 4% as well as reductions in the secondary end points of biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years. The Gleason score was the only independent prognostic predictor for all end points measured. The lack of surgical staging for regional lymph nodes did not predict poor outcomes, validating the current practice of clinical staging in patients receiving radiotherapy. The efficacy gains were achieved with minimal temporary acute hepatic toxic effects and some decreased erectile function at 1 year, but with no increased risk of death from intercurrent disease, serious cardiovascular toxic effects, or acute or long-term gastrointestinal or genitourinary complications of radiotherapy. The rate of erectile dysfunction observed in this study is similar to that reported in previous studies that involved the use of similar doses of radiotherapy.

Reanalysis of the data according to risk subgroups showed that the gains in overall survival and reductions in disease-specific mortality were mainly limited to men in the intermediate-risk subgroup, with a number needed to treat of 14 based on the difference in overall survival seen at 10 years. Although the addition of short-term ADT to radiotherapy also appeared to be beneficial in the high-risk patients, the persistent significant increase in 10-year disease-specific mortality provides support for observations from other clinical trials showing that more than 4 months of ADT is required for maximum benefit.

Among men with low-risk disease, the addition of short-term ADT did not significantly increase the 10-year rate of overall survival or decrease the 10-year rate of disease-specific mortality but did significantly lower the incidence of biochemical failure and positive findings on repeat prostate biopsy at 2 years. It is conceivable that in patients with indolent disease, longer follow-up is required to show a benefit with respect to the diseasespecific mortality and overall survival rates.