Challenges in treating advanced disease.

Castration-resistant prostate cancer (CRPC) has historically presented significant challenges to both clinicians and patients in regard to disease progression and consequent management. The first advances in the treatment of this state of prostate cancer with docetaxel chemotherapy demonstrated a survival benefit over the palliative standard of care, mitoxantrone combined with prednisone. The recognition that these patients still maintained active androgen receptor access identified new therapeutic agents for CRPC that aimed to further deplete testosterone levels or directly interact with the androgen receptor (ie, enzalutamide). Other therapeutic targets that have established efficacy in randomized phase 3 trials include bone metastases (ie, radium 223 dichloride), the immune system (ie, sipuleucel-T), and tubulin (ie, cabazitaxel). These new and evolving agents are positioned to substantially alter the therapeutic environment for CRPC and to improve patient outcomes and quality of life.