Adding short-term androgen-deprivation therapy to radiotherapy “conferred a modest but significant increase in the 10-year rate of overall survival, from 57% to 62%,” in men with localized prostate cancer enrolled in Radiation Therapy Oncology Group (RTOG) trial 94-08. “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, the RTOG investigators reported in The New England Journal of Medicine.
The study involved 1,979 men with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level ≤ 20 ng/mL who were randomly assigned to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (987 patients). 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. Trial participants had not received any previous chemotherapy, radiation or hormonal therapy, cryosurgery, or definitive treatment for prostate cancer.
The RTOG investigators found that “the greatest clinical benefit” was to men in the intermediate-risk subgroup.” Men in this group had a baseline Gleason score of 7 or ≤ 6 with a PSA level > 10 and ≤ 20 ng/mL or clinical stage T2b.
“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 authors reported. “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 that newer radiotherapy techniques permit “safer delivery of higher does of radiation than was possible when this study was conducted” and are associated with improved efficacy. A new study (RTOG 081-15) is looking at adding the value of short-term androgen-deprivation therapy in men with intermediate-risk cancers treated with these current irradiation methods.
Jones CU, et al: N Engl J Med 365:107-118, 2011.