The addition of short-term androgen deprivation therapy to radiotherapy for men with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng/mL or less “conferred a modest but significant increase in the 10-year rate of overall survival, from 57 to 62%,” investigators reported. “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 endpoints of biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years,” they added.
Radiation Therapy Oncology Group (RTOG) trial 94-08, summarized in an article in The New England Journal of Medicine, randomly assigned 992 patients to radiotherapy alone and 987 patients to radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy. The total radiation dose was 66.6 Gy to the isocenter. Androgen deprivation therapy consisted of flutamide at 250 mg orally three times a day and either monthly subcutaneous goserelin (Zoladex) at 3.6 mg or intramuscular leuprolide at 7.5 mg for 4 months. Flutamide was discontinued if alanine aminotransferase increased to more than twice the upper limit of the normal range.
Risk-Benefit Considerations
“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,” the authors noted. “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,” they added.
“Although combined therapy appears to be indicated in men with intermediate-risk disease, whether a radiation dose of more than 66.6 Gy or longer durations of hormonal therapy can reduce mortality further is unknown,” Anthony V. D’Amico, MD, PhD, commented in an accompanying editorial. “Whether 4 or 6 months of hormonal therapy for intermediate-risk disease is best requires further study.”
Jones CU, et al: N Engl J Med 365:107-118, 2011.
D’Amico AV: N Engl J Med 365:169-171, 2011
