Castration-resistant prostate cancer: many treatments, many options, many challenges ahead

Although the long natural history of prostate cancer presents challenges in the development of novel therapeutics, major contributions have been observed recently. A better understanding of the long-term complications of androgen deprivation has changed the initial approach to most patients with advanced disease. Specifically, recognition of the limitations of prostate-specific antigen has driven the pursuit of new tools capable of becoming true surrogates for disease outcome. Understanding the molecular biology of castration-resistant prostate cancer (CRPC) has led to a dramatic paradigm shift in the treatment of patients with metastatic disease where the androgen receptor becomes a central therapeutic target. Specific adrenal inhibitors and engineered super androgen receptor inhibitors have become the most promising agents in the disease. Novel immune therapies have been shown to improve survival in selected patients with castration-resistant disease despite the inability to impact traditional markers of response. Similarly, agents such as cabazitaxel and abiraterone acetate have demonstrated clinical benefit are now a standard of care in docetaxel-refractory metastatic CRPC patients. All these changes have occurred in a relatively short period and are likely to change the prostate cancer treatment paradigm. This review summarizes the current management of CRPC and discusses potential future directions.