Intermittent Androgen Suppression Therapy for Prostate Cancer Patients: A Choice for Improved Quality of Life?

Prostate cancer is among the most common types of malignancies and causes of cancerrelated deaths in men worldwide (Fitzpatrick, et al., 2009). Primary tumor involvement outside the prostatic capsule or relapse following radical prostatectomy results generally in incurability (Lassi & Dawson, 2009). Androgen deprivation therapy has progressed since attempts in 1941, when surgical castration had been shown to improve outcomes for the first time. Palliative treatment consists of hormonal manipulation to deprive the cancer cells of androgenic stimulation by orchidectomy or use of LHRH analogs and steroidal or nonsteroidal antiandrogens (Kollmeier & Zelefsky, 2008). Although continuous androgen suppression therapy (CAS) has been a cornerstone of the management of prostate cancer for more than 50 years, controversy remains regarding its optimum application. Generally, androgen suppression (AS) is performed as continuous treatment, resulting in apoptotic regression of the tumor cells in a high percentage of cases. However, surgical or medical castration results in median progression-free survival of only 2–3 years, with no other effective treatment left (Mellado, et al., 2009). Responses to cytotoxic therapy are low and only recently several studies revealed a possible benefit of incorporating chemotherapeutic agents in treatment regimen for prostate cancer (Chang & Kibel, 2009). Taxanes like docetaxel and cabazitaxel, therapeutic cancer vaccines and newly developed agents targeting androgen receptor signaling are expected to improve therapy (Madan et al., 2011). Following experimental research using animal models, intermittent androgen suppression (IAS) was introduced as new clinical concept, assuming that during limited regrowth in the treatment cessation periods tumorigenic cells are residing in an androgen-responsive state (Goldenberg, et al., 1995). Since induction of androgen independence may occur early after treatment initiation, cessation of antiandrogen therapy prior to this switch is expected to maintain the apoptotic potential of the tumor cells and keep them sensitive to retreatment. Providing an easy method for selection of the type of treatment and early assessment of tumor growth during the off-periods serial serum PSA determinations made IAS feasible. In detail, IAS consists of an initial androgen suppression period of up to nine months combining LHRH antagonists and antiandrogens, which is followed by treatment cessation