Evolving therapeutic paradigms for advanced prostate cancer.

Improving survival in metastatic castration-resistant prostate cancer (CRPC) is no longer an elusive goal. With the expansion of knowledge regarding the biology of the disease, we are witnessing a plethora of novel therapeutics that are undergoing testing in clinical trials. Since the approval of docetaxel for metastatic CRPC in 2004, three additional agents have demonstrated improvements in overall survival in randomized phase III trials: two agents (cabazitaxel and sipuleucel-T) were approved by the FDA in 2010, and a third (abiraterone) was approved in April of 2011. A threshold has clearly been crossed in the management of advanced prostate cancer; however, the impact on survival has been relatively modest, and efforts at personalized therapy have lagged behind those for other solid tumors. Further meaningful advances are needed, and the foundation for future clinical trials must be high-quality, high-impact translational science that focuses on disease biology, the defining of relevant pathways and validated predictive biomarkers, and adequate preclinical characterization of agents and combinations that will facilitate more personalized therapy.