BACKGROUND
It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma.

METHODS
From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years.

RESULTS
The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P = 0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P = 0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiationinduced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate- risk patients, with no significant reductions among low-risk patients.

CONCLUSIONS
Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men.

In the 1980s, advances in both surgery and radiotherapy for clinically localized prostate cancer led to their acceptance as successful treatments, with considerable reductions in harmful side effects as compared with earlier treatments. In the 1990s, reversible androgen suppression with the use of luteinizing hormone–releasing hormone analogues and oral antiandrogen agents was shown to induce apoptotic regression in androgen- responsive cancers, potentially improving the prospects of local control and the duration of survival free of metastatic disease. Among patients with locally advanced disease, phase 3 clinical trials showed that when added to radiotherapy, long-term treatment with these agents (≥2 years) improved overall survival but also increased toxic effects, including erectile dysfunction and myocardial infarction.5 Short-term androgendeprivation therapy (ADT) could potentially mitigate these toxic effects. A Radiation Therapy Oncology Group (RTOG) phase 3 clinical trial, reported in 1994, showed that short-term ADT administered for 4 months before and during radiation therapy significantly improved local control and disease-free survival among patients with bulky stage T2c to T4 tumors. Other trials have also shown benefits from this approach.