NEJM: ADT lowers prostate cancer mortality
With the induction of prostate-specific antigen (PSA) testing, the volume of early-stage prostate adenocarcinoma diagnoses has increased, accompanied by growing use of short-term ADT in patients undergoing radiotherapy. Although early results appear promising, knowledge of the efficacy and adverse toxic effects of ADT before and during radiotherapy is incomplete, indicated Christopher U. Jones, MD, from Radiological Associates of Sacramento in California, and co-authors.
As part of the Radiation Therapy Oncology Group (RTOG) trial 94-08, Jones and colleagues enrolled 1,979 patients with prostate adenocarcinomas at stage T1b, T1c, T2a or T2b. Only patients with PSA levels at or below 20 ng per mL were included in the study.
Nine hundred ninety-two patients were treated with radiotherapy only (66.6 Gy), while 987 patients received radiotherapy (also 66.6 Gy) plus short-term ADT. Therapy consisted of 250 mg of flutamide three times daily and monthly injections of either goserelin or leuprolide. Median follow-up was approximately 9.1 years.
Patients treated with radiotherapy and ADT showed significant benefits. The 10-year overall survival rate was 57 percent in the radiotherapy-alone group and 62 percent in the radiotherapy plus ADT group, while disease-specific mortality was 8 percent in the radiotherapy-alone group and 4 percent in the combined-therapy group.
ADT likewise appeared to lower the risk of recurrence, with biochemical failure rates of 41 percent in the radiotherapy-alone group and 26 percent in the ADT plus radiotherapy group. Ten-year cumulative incidence of distant metastases was 2 percent lower in the combined-therapy group (8 vs. 6 percent).
Sub-group analysis also revealed that blacks and whites benefited equally from the addition of ADT. Patients with intermediate-risk disease had the most dramatic improvements from ADT, with 10-year overall survival increasing from 54 percent in the radiotherapy-along group to 61 percent with the addition of ADT for intermediate-risk patients. Ten-year disease-specific mortality fell from 10 to 3 percent in this group as well.
Low-risk patients did not experience a significant improvement in survival or disease-specific mortality from ADT. High-risk patients appeared to receive some benefit from ADT, though the authors hypothesized—based on findings from other trials—that ADT might need to be extended for longer than four months for patients to experience the therapy’s maximum effect.
ADT did appear to result in small, temporary increases in hepatic toxicity and decreased erectile function at one year. No increase in the risk of inter-current disease, serious cardiovascular toxic effects or acute long-term gastrointestinal or genitourinary complications were observed.
“The results of our trial show that the addition of short-term ADT provides a survival benefit for men with intermediate-risk prostate cancer who receive conventional doses of radiotherapy. In addition, our findings suggest a biologic interaction between short-term ADT and radiotherapy, in contrast to several randomized trials of surgery combined with short-term ADT, which did not show a benefit with respect to outcome,” Jones and colleagues concluded.
They added, though, that the more recent adoption of higher-dose but safe radiotherapy techniques, such as intensity-modulated radiotherapy, intensity-guided radiotherapy and brachytherapy, could alter the positive effects conferred by ADT. An additional RTOG study has been opened, the authors said, to investigate this possibility.