1. The addition of biclutamide (antiandrogen) to radiation therapy for recurrent prostate cancer improved overall survival compared to radiation alone.
2. Radiation therapy and biclutamide resulted in lower incidences of metastatic, and death from, prostate cancer.
Evidence Rating Level: 1 (Excellent)
Study Rundown: For patients with localized prostate cancer a recurrence greater than 30% has been anticipated after a radical prostatectomy. Despite salvage radiation therapy, half of these men will have disease progression. Prior studies have shown androgen deprivation or anti-androgen therapy, in addition to radiation, can prolong metastasis free survival and overall survival in men with recurrent prostate cancer. Though gonadotropin releasing hormone (GnRH) agonists are currently used more often, the long-term follow-up on therapy using anti-androgens is the subject of this trial. This double-blind, randomized controlled trial compared salvage radiation therapy and biclutamide (androgen receptor blocker) for 24 months versus radiation plus placebo in men with recurrent prostate cancer. The trial arm showed a significant improvement in overall survival at 12-years post treatment. In addition, there were lower rates of metastatic and death from prostate cancer at the 12-year mark. An important strength of this trial was the design of the research trial, large study numbers and long-term follow-up data. The main limitation is that biclutamide has been superseded by the use of GnRH agonists in current practice.
In-Depth [randomized controlled trial]: This was a double-blind, placebo-controlled trial completed between 1988 and 2003 involving 840 eligible men who underwent radical prostatectomy and lymphadenectomy. The participants were stage T2 (disease confined to the prostate, with positive surgical margin), or T3 (prostatic extension) with no nodal involvement. All patients had radiation therapy (64.8 Gy in 36 daily fractions, five sessions per week), and either received 24 months of biclutamide (150mg daily) or daily placebo. The primary endpoint was the rate of overall survival.
A total of 760 participants were eligible for the study. The median follow-up of surviving patients was 13 years. A total of 21 patients died from prostate cancer in the biclutamide group, compared to 46 in the placebo group. The actuarial rate of survival was 76.3% in the biclutamide group at 12 years, and 71.3% in the placebo group (HR for death, 0.77; 95% CI 0.59-0.99, p = 0.04). The 12-year incidence of death from prostate cancer in the biclutamide group was 5.8% compared to 13.4% in the placebo group (HR 0.49; 95% 0.32-0.74, p < 0.001). The cumulative incidence of distant metastases was 14.5% in the biclutamide group at 12 years compared to 23% in the placebo group (HR 0.63; 95% CI 0.46-0.87; p = 0.005).
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