Effect of delayed maximal androgen blockade therapy for patients with advanced prostate cancer who fail to respond to initial androgen deprivation monotherapy.

Objectives: We analyzed the efficacy of additional antiandrogens as second- and third-line treatments after the failure of initial androgen deprivation monotherapy.
Methods: This retrospective study included 53 patients with advanced prostate cancer initially treated with androgen deprivation monotherapy alone. An antiandrogen was added to androgen deprivation monotherapy as the second-line treatment after the failure of the initial androgen deprivation monotherapy. Another antiandrogen, estrogen or steroid was given as the third-line treatment after the second-line treatment failed.
Results: The initial androgen deprivation monotherapy was effective in all 53 patients for a median of 9.6 months. Thirty-three (62.3%) patients showed a prostate-specific antigen response to the second-line treatment for a median of 10.7 months. Of the 46 patients who received the third-line treatment, 16 (34.8%) showed a prostate-specific antigen response for a median of 6.0 months. Patients who responded to the second-line treatment had a significantly higher cancer-specific survival rate than those without a response. In multivariate analysis, a nadir prostate-specific antigen of 4.0 ng/ml or greater during androgen deprivation monotherapy and prostate-specific antigen doubling time of less than 10 months after androgen deprivation monotherapy failure were independent risk factors for prostate cancer death after androgen deprivation monotherapy failure, with hazards ratios of 5.59 and 8.00, respectively. The 5-year cancer-specific survival rates were 100%, 65.0% and 15.5% in patients with 0, 1 and 2 risk factors, respectively (P = 0.047).
Conclusions: In this study, the second- and third-line treatments were effective for patients with advanced prostate cancer. Nadir prostate-specific antigen during androgen deprivation monotherapy and prostate-specific antigen doubling time just after the failure of androgen deprivation monotherapy are factors that can predict the prognosis.