BERKELEY, CA (UroToday.com) - While high dose bicalutamide therapy (150 mg/day) has the theoretical advantage of hormonal blockade with less sexual side effects or physical complications than LHRH agonists, its use is controversial and currently not approved by the FDA in part because of its potential cardiovascular toxicity. Furthermore, nonsteroidal antiandrogen monotherapy is well known to result in gynecomastia and mastalgia. In the Early Prostate Cancer Program (EPC), the reported incidence of breast enlargement or pain was 68% and 73%, respectively. The traditional prevention strategy utilized has been prophylactic low-dose breast irradiation with an efficacy ranging between 50 and 75%. Recent reports have suggested that tamoxifen may also play a role in the prevention of gynecomastia in these patients.

In the December issue of the Journal of Urology, Di Lorenzo et al report data from a multi-institutional study comparing the efficacy of radiotherapy or tamoxifen for this purpose in patients treated with high dose bicalutamide after radical prostatectomy. Furthermore, the impact of these treatments on hormonal status, quality of life, sexual function, and biochemical recurrence was assessed.

A total of 102 patients who underwent radical prostatectomy treated with adjuvant high dose bicalutamide were randomized to 3 groups: (1) observation with delayed randomization to tamoxifen or RT with the development of gynecomastia, (2) tamoxifen 10 mg, or (3) prophylactic breast irradiation.

The incidence of gynecomastia was 67% in group 1, 8% in group 2, and 34% in group 3. Breast pain was more frequent in group 1 than in groups 2 and 3 (58% vs. 7% and 30%, respectively). The slight improvement seen in the tamoxifen group compared with the RT group was not statistically significant. However, of the 22 patients in group 1 who developed gynecomastia, tamoxifen was more effective than RT in reversing gynecomastia (91% vs. 46%) and breast pain (80% vs. 22%) (P < 0.05). There were no differences in quality of life or sexual function between groups 2 and 3. An equal number of patients recurred in the 3 groups after a median follow-up of 26 months.

This well designed study with a small sample size suggests that tamoxifen is at least as effective as prophylactic breast RT in preventing gynecomastia and breast pain induced by bicalutamide monotherapy. Most importantly, in patients who developed this complication, tamoxifen was more effective in reversing gynecomastia and breast pain when compared to RT. While these data are encouraging, longer follow-up from a larger cohort of patients is needed to ensure that tamoxifen does not adversely impact prostate cancer recurrence in these patients.

J Urol. 2005 Dec; 174(6):2197-203