Short vs. long-term androgen deprivation therapy: The jury is still out

January 1, 2008

Further analysis of completed studies, along with the completion of ongoing trials, will hopefully clarify the optimal length of adjuvant ADT

Anthony D'Amico, MD, and colleagues present a very important and timely study comparing different treatment courses of ADT in conjunction with radiation therapy (see, "Ideal length of androgen ablation still debated," page 1). They analyzed data from three randomized, controlled trials to evaluate the effectiveness of 6 months versus 3 years of ADT following radiation therapy for locally advanced or high-grade prostate cancer. After adjusting for known prognostic factors, the age-adjusted survival rates 5 years following randomization were 83% for those receiving 6 months versus 78% for those receiving 3 years of ADT plus radiation therapy.

A recent secondary analysis of data from RTOG 85-31 argues against this approach, suggesting a longer duration of ADT may be appropriate (see, "Adjuvant hormonal therapy: Longer duration is better," Urology Times, Oct. 1, 2007, page 1). This trial enrolled 977 men, and the re-analysis consisted of 377 patients who were treated with ADT for either 6 years or less or for longer than 6 years. The authors reported statistically significant differences favoring men treated for greater than 6 years relative to those treated for a shorter period on the basis of disease-specific and overall survival. However, this study was not powered for such an analysis, and these patients were clinically staged T3 or pN+, whereas the D'Amico trial enrolled only patients with clinically localized, non-node-positive disease.

The jury is still out on the optimal length of adjuvant ADT after radiation therapy in men with high-risk prostate cancer. Dr. D'Amico states that in older men with node-negative disease, short-term ADT is likely all that is needed, even in patients with Gleason 8 to 10 disease. However, for younger or node-positive men, this may be inadequate. Further analysis of the data is required before a short course of ADT is used. Although men would prefer a shorter course and urologists would agree to reduce the drugs' potential side effects, we must proceed with caution given the uncertainties noted among these studies. Further analysis of completed studies, along with the completion of ongoing trials, will hopefully clarify the optimal length of adjuvant ADT.

J. Brantley Thrasher, MD