Prophylaxis for Treatment-Induced Gynecomastia in Prostate Cancer Patients: A Network Meta-Analysis.

Abstract

Treatment-induced gynecomastia is a side-effect that can severely limit quality of life in prostate cancer patients. We performed a network meta-analysis (NMA) to comparing the effectiveness of multiple non-surgical prophylactic treatment for gynecomastia. A systematic review was performed through MEDLINE, Cochrane Central Register of Controlled Trials and meeting abstracts to identify randomized controlled trials comparing treatments for treatment-induced gynecomastia. Treatments included radiotherapy (RT), Anastrozole (ANZ), daily Tamoxifen (TMQD), and weekly Tamoxifen (TMQW), compared to no treatment/placebo (NoTx). The primary endpoint was events of gynecomastia development. Odds Ratio (OR) was the effect size of choice. An NMA was used to compare treatments with random-effects model was used. All tests were 2-sided with an alpha of 0.05. A total of 9 studies involving 1319 patients were identified with 5 distinct arms: RT (n = 358), ANZ (n = 90), TMQD (n = 321), TMQW (n = 39) and NoTx (n = 511). Gynecomastia occurred in 79.2% (405/511) of patients with NoTx, 65.5% (59/90) with ANZ, 37.7% (135/358) with RT, 19.6% (63/321) with TMQD and 74.4% (29/39) with TMQW. TMQD was significantly better than RT (OR 4.73 [1.53, 14.61]), ANZ (OR 7.21 [2.25,23.06]), TMQW (OR 6.25 [1.07, 36.43]) and NoTx (OR 26.30 [10.42,66.40]). RT were significantly better than NoTx (OR 5.56 [2.58,11.95]), but did not reach significance compared to ANZ (OR 1.52 [0.36, 6.43]) or TMQW (OR 1.32 [0.16, 10.70]). ANZ was significantly better than NoTx (OR 3.65 [1.03,12.93]). TMQW was not significantly better than NoTx. RT, TMQW and ANZ were significantly worse compared to TMQD in terms of preventing gynecomastia development. Daily Tamoxifen was the best prophylactic treatment choice, significantly better than RT, weekly Tamoxifen and Anastrozole. RT, weekly Tamoxifen and Anastrozole were significantly better than No Treatment/Placebo, but not daily Tamoxifen, in terms of prevention of treatment-induced gynecomastia in patients with prostate cancer.