Alternative Antiandrogen Therapy for CRPC

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Androgen deprivation therapy continues to be a mainstream treatment for prostate cancer. Failure after initial hormonal treatment including combined androgen blockade (CAB)/maximum androgen blockade (MAB) does not necessarily imply treatment-refractory disease progression. Antiandrogen withdrawal syndrome (AWS) is a manifestation of a prostate-specific antigen (PSA) decrease with or without subjective or objective symptomatic improvement on discontinuation of the antiandrogen. In general, the incidence of this effect has been reported to be 10–30%, and it lasts for 3–5 months. Some patients with progressive disease who have undergone initial CAB/MAB therapy respond to second- and third-line hormonal therapy after AWS is recognized. Mutations in the androgen receptor (AR) gene are thought to account for this phenomenon by enabling the previous antiandrogens to act as receptor agonists. Alternative antiandrogens probably have different functional interactions with the AR. Alternative antiandrogen therapy has been shown to improve symptoms and decrease pain in patients with prior antiandrogen therapy. A 50% PSA decrease has been reported after second-line treatment with nonsteroidal antiandrogens in 35–50% of cases. Responders to second-line hormonal treatment are expected to survive significantly longer than nonresponders. Responsiveness to second-line regimens is the most important prognostic factor for increased cause-specific and overall survival.