Effect of nonsteroidal antiandrogen monotherapy versus castration therapy on neuroendocrine differentiation in prostate carcinoma

Objectives. To determine whether the ad ministration of the nonsteroidal antiandrogen bicalutamide reduces the risk of an increase in chromogranin A (CgA) levels in patients with prostate cancer who experienced biochemical failure after radical retropubic prostatectomy (RRP) compared with pharmacologic castration therapy. It has been hypothesized that continuous androgen suppression for the treatment of prostate cancer results in hyperactivation of neuroendocrine cells and an increase in CgA levels. Methods. Forty-eight patients with pT3pN0M0 prostate cancer and biochemical (prostate-specific antigen) progression after RRP were randomized to bicalutamide monotherapy or pharmacologic castration. The serum levels of CgA and prostate-specific antigen were measured at 1, 3, 6, 12, 18, and 24 months of therapy. The changes in serum CgA levels were compared for patients who successfully responded to the first 24 months of therapy. Results. In both treatment groups, a statistically significant trend was noted for CgA levels to increase from baseline to 24 months. This trend was lower in the bicalutamide group (slope = 0.60, 95% confidence interval 0.28 to 0.92; P = 0.004) than in the castration group (slope = 0.29, 95% confidence interval 0.08 to 0.50; P = 0.01). Conclusions. The results of this study provide the first evidence to show that in patients with prostate cancer undergoing hormonal therapy, nonsteroidal antiandrogen monotherapy produces a significantly lower increase in serum CgA compared with castration.