Advances in the treatment of metastatic prostate cancer

Prostate cancer is the most common cancer in men in the UK. It accounts for nearly a quarter of all male cancer diagnoses and is the second most common cause of male cancer death. Despite a large increase in prostate cancer incidence, mortality rates have remained relatively constant through improvements in survival. Most patients present with localised disease, but there are still many who present with metastatic disease. Prostate cancers are driven by androgens, such as testosterone. Androgen deprivation therapy (ADT), which is still the mainstay of systemic treatment, effectively reduces intraprostatic androgen levels resulting in reduced androgen receptor (AR) stimulation and increased apoptosis. Medical castration using LHRH analogues has become the gold standard in managing both locally advanced prostate cancer, in ombination with radiotherapy, and metastatic disease. Eventually most men with advanced prostate cancer become resistant to ADT. This is now called castrate refractory prostate cancer (CRPC), and is associated with a poor prognosis. There is now hope for patients who progress after chemotherapy with the emergence of several new agents that have been shown to benefit patients. The first AR-targeted drug to show a definite clinical benefit is abiraterone. It markedly decreases levels of androgens in CRPC and initial trials showed promising activity. Enzalutamide has a high affinity and selectivity for AR binding, blocks nuclear translocation and reduces recruitment of co-activators. Abiraterone, enzalutamide and other AR-targeted drugs are being studied in clinical trials for patients earlier in their disease, e.g. in addition to ADT at first presentation of metastatic disease, where it is likely that greater benefits will be seen.