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 ≥ 5ng/dl.