Short-Term vs. Long-Term Hormone Therapy for Prostate Cancer

Given emerging data about the potential harms of androgen-deprivation therapy (ADT), the need is growing to define the optimal duration of ADT plus external beam radiotherapy for patients with locally advanced prostate cancer. Although level 1 evidence suggests that radiotherapy plus short-term (6 months) ADT attenuates disease mortality in patients with clinically localized prostate cancer, no current data support this approach in patients with higher-risk disease.

To examine this issue, European investigators assessed 970 men with locally advanced prostate cancer. Patients received external beam radiotherapy (70 Gy) plus ADT for 6 months. Those with no evidence of disease progression were then randomized to receive either no additional ADT (short-term group) or 2.5 years of additional ADT (long-term group). Quality of life was assessed using a validated questionnaire. The primary endpoint was overall survival assessed with a modified log-rank test for noninferiority.

During median follow-up of 6.4 years, 132 deaths (47 from prostate cancer) occurred in the short-term group, and 98 deaths (29 from prostate cancer) occurred in the long-term group. Five-year overall mortality was 19.0% in the short-term group and 15.2% in the long-term group; these results did not fit with the hypothesis that the outcomes would be similar between the short-term and long-term groups. The investigators noted no serious long-term genitourinary or gastrointestinal toxicity from radiotherapy and no elevated risk for fatal cardiovascular events. Insomnia, hot flushes, and diminished sexual interest and activity were more common in the long-term group. However, no between-group differences in overall quality of life were seen. The authors concluded that the combination of radiotherapy plus 6 months of ADT is inferior to radiotherapy plus 3 years of ADT.