Stepping-stones to the further advancement of androgen-deprivation therapy for prostate cancer

Androgen-deprivation therapy has remained the critical therapeutic option for patients with advanced prostate cancer for over 60 years. Patients with poorly differentiated prostate cancer have low dihydrotestosterone levels in the prostate. After androgen-deprivation therapy, dihydrotestosterone levels in the prostate remain at approximately 25% of the level measured before therapy. The addition of a nonsteroidal anti-androgen to luteinizing hormone-releasing hormone analog or surgical castration significantly reduces the risk of all causes of death by 8%, which translates into a small, but significant, improvement in the 5-year survival of 2.9% over castration alone. The biologically aggressive prostate cancer cells may have an androgen receptor with heightened sensitivity to low dihydrotestosterone levels from the early stage of androgen-dependent disease. It is necessary to consider the androgen environment and the status of the androgen receptor in the prostate in order to improve the clinical efficacy of androgen-deprivation therapy and the quality of life of patients.