Serum Testosterone Level to Predict the Efficacy of Sequential Use of Antiandrogens as Second-line Treatment Following Androgen Deprivation Monotherapy in Patients with Castration-resistant Prostate Cancer

Objective: We investigated whether serum testosterone after the failure of androgen deprivation monotherapy predicted the efficacy of antiandrogens added to androgen deprivation monotherapy as second-line treatments for patients with castration-resistant prostate cancer. Methods: We reviewed 30 patients with castration-resistant prostate cancer who received maximal androgen blockade with addition of an antiandrogen (delayed maximal androgen blockade) (bicalutamide 80 mg daily for 21 patients and flutamide 375 mg daily for 9 patients) as the second-line treatment. The patients were divided into two groups by serum testosterone before delayed maximal androgen blockade: 22 in the testosterone >= 5 ng/dl group and 8 in the testosterone < 5 ng/dl group. A prostate-specific antigen response was defined as a prostate-specific antigen decline of >= 50% from the pre-treatment level. Results: The response rate was significantly higher in the testosterone >= 5 ng/dl group than in the testosterone < 5 ng/dl group (77.3 vs. 37.5%, P = 0.04). During the median follow-up period of 52.5 months, 24 patients (80.0%) developed prostate-specific antigen progression. A serum testosterone level of < 5 ng/dl was an independent factor to predict prostate-specific antigen progression in a reduced and full model setting on multivariate analysis (hazard ratio 6.03, P = 0.003 and 5.99, P = 0.003, respectively). The 1-year prostate-specific antigen progression-free survival rate was significantly higher in the testosterone >= 5 ng/dl group than in the testosterone < 5 ng/dl group (52.9 vs. 0%, P = 0.002), as was cause-specific survival (5 years: 66.0 vs. 33.3%, P = 0.007). Conclusions: Serum testosterone could play an important role when delayed maximal androgen blockade is indicated as the second-line treatment in patients with castration-resistant prostate cancer. Delayed maximal androgen blockade might be more beneficial in patients with a serum testosterone level of >= 5 ng/dl.