A long-term study found that adding 24 months of antiandrogen therapy with bicalutamide to salvage radiation therapy (RT) increased overall survival and prostate cancer–specific survival compared with placebo in men who underwent radical prostatectomy.
Previous work has shown that salvage RT can help prevent recurrence after radical prostatectomy, but 50% of patients who receive this therapy will still have further disease progression.
“The combination of RT and either androgen-deprivation therapy or antiandrogen therapy prolongs survival among some men with an intact prostate,” wrote study authors led by William U. Shipley, MD, of Massachusetts General Hospital in Boston. “Thus, this combination treatment represents a rational approach to prolong metastasis-free survival and overall survival among men with a postoperative recurrence.”
The new study was a double-blind, randomized trial conducted between 1998 and 2003. A total of 760 patients who had undergone prostatectomy with lymphadenectomy and had disease, no nodal involvement, and a detectable prostate-specific antigen (PSA) level of 0.2 to 4.0 ng/mL were randomized to either 2 years of antiandrogen therapy with daily bicalutamide (384 patients) or to placebo (376 patients). The results of the study were published online ahead of print in the New England Journal of Medicine.
The median age of patients was 65 years, and the median PSA level at study entry was 0.6 ng/mL. The median follow-up was 13 years. At the 12-year mark, 21 patients in the bicalutamide group had died due to prostate cancer, compared with 46 placebo patients. The actuarial rate of overall survival at 12 years was 76.3% with bicalutamide and 71.3% with placebo, for a hazard ratio (HR) of 0.77 (95% CI, 0.59–0.99; P = .04).
The 12-year prostate cancer-specific death rates were more strongly in favor of the antiandrogen therapy arm. That group had a 12-year rate of 5.8%, compared with 13.4% with placebo, for an HR of 0.49 (95% CI, 0.32–0.74; P < .001).
The cumulative incidence of distant metastases was also improved with the intervention, with a rate of 14.5% with bicalutamide and 23% with placebo, for an HR of 0.63 (95% CI, 0.46–0.87; P = .005). Incidence of second biochemical recurrence was also better with bicalutamide. A PSA level at baseline above 1.5 ng/mL was a significant negative prognostic factor for overall survival, as was a Gleason score of 8 to 10 at entry, a Karnofsky performance status score of 80 or 90, or age of 65 years or older. The rates of late adverse events were similar between the two groups, though gynecomastia was more common with bicalutamide.
The study authors noted that 20 years after this study was designed other drugs—GnRH agonists—have replaced bicalutamide as the first choice for hormonal therapy with RT, and thus these results are only a “proof of principle.” Another study is currently testing the concept with contemporary androgen-deprivation therapy.
In an accompanying editorial, Ian M. Thompson, Jr, MD, of the Christus Santa Rosa Health System in San Antonio, Texas, noted that despite guidelines calling for salvage RT at the time that PSA becomes detectable, it is often not administered or delayed. “The benefit of the conclusions of this trial can be accrued only if salvage RT is administered appropriately,” he wrote. “This is clearly an opportunity for national quality-improvement initiatives.”