Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab). Given that docetaxel was the standard first line treatment for metastatic CRPC, the newer oral agents that affect the androgen axis were initially approved in the post-docetaxel setting. However, subsequent randomized trials have led to their approval in the pre-chemotherapy setting as well. Patients with CRPC are clinically heterogeneous, ranging from patients who are asymptomatic and do not have metastases to those with substantial symptoms and both bony and visceral metastases. CRPC is a clinically challenging disease entity, therefore, with a wide array of treatment options and multiple possible sequencing combinations depending on the individual patient. This review will summarize the findings of the randomized trials that led to the approval of the therapies for CRPC. It will also discuss recent guidelines and provide suggestions for sequencing of drugs based on the best available evidence.
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