The changing landscape of advanced and castration resistant prostate cancer: latest science and revised definitions.

INTRODUCTION One fifth of men with newly diagnosed prostate cancer present with locally advanced or metastatic disease. Androgen deprivation therapy (ADT) is the standard systemic therapy in these patients. Despite initial response, essentially all patients will develop castration resistant prostate cancer (CRPC). In this review, we will discuss the revised definitions of CRPC and the latest understanding of the biology of the androgen/androgen receptor axis in the development of advanced prostate cancer. MATERIALS AND METHODS A systematic literature review was conducted via electronic database articles based on title, abstract, study format, and content. The majority of selected articles were published between 1992 and 2013. Older studies were included selectively if historically relevant. RESULTS Prostate cancer becomes castration resistant through numerous pathways, including androgen and androgen receptor (AR) dependent mechanisms as well as ligand and AR independent pathways. Therefore the terms androgen-insensitive and hormone-refractory should be avoided and replaced by the term castration resistant. Recent advances in understanding molecular mechanisms of castration resistance have led to development of novel CRPC therapeutics. CONCLUSIONS CRPC remains an incurable disease. Further understanding of the pathways involved in castration resistance will set the basis for development of therapies to increase survival in these patients.