Novel therapeutics for the management of castration-resistant prostate cancer (CRPC).

ABSTRACT

Androgen-deprivation therapy is the initial treatment for metastatic prostate cancer. Although highly effective, all men who live long enough will eventually experience disease progression and develop castration resistance. Patients who have castration-resistant prostate cancer (CRPC) have a median survival of ≈1-3 years. When evaluating novel therapies for CRPC, one must consider the endpoints measured for determination of response. We will discuss PSA, circulating tumour cells, progression-free survival, overall survival, and other endpoints used in clinical trials. Docetaxel and sipuleucel-T are currently the preferred first-line treatment options for patients with CRPC; cabazitaxel is a new option for patients after docetaxel failure. Patients with CRPC historically have very poor survival, underscoring the unmet need for novel therapeutics. Although many agents appear promising, well-designed randomized phase III trials are necessary to establish their impact on survival and health-related quality of life. Promising new therapies include hormonal agents, such as abiraterone and MDV3100, as well as other novel immunotherapeutics and anti-prostate-specific membrane antigen therapies. In the future, we anticipate therapies tailored to individual patients' malignancies using various molecular analyses.