Therapy selection for metastasized castration-resistant prostate cancer

Various therapeutic options with different mechanisms of action are available for the treatment of castration-resistant prostate cancer (CRPC). This article gives an overview of the different therapeutic strategies for the treatment of CRPC. Summary of landmark trials with supplementary information for the approved medications, potential therapeutic sequences as well as pipeline medication from Medline and abstracts of international congresses (e.g. ASCO and ASCO GU). Enzalutamide and abiraterone both act via the androgen receptor signal transduction pathway and can be applied before and after docetaxel; however, the approval before chemotherapy is limited to mildly symptomatic or asymptomatic disease. Alpha-emitting radium-223 is a good option for men suffering from symptomatic metastatic disease limited to the bone because the compound mimics calcium and is thus incorporated into bone lesions. In the second line setting cabazitaxel is an additional option. This semisynthetic taxane derivative is so far the only chemotherapy resulting in a prolongation of overall survival after docetaxel failure. Only few retrospective data concerning the optimal therapeutic sequence are available to date but a decrease of tumor response has been observed with each additional course of treatment. Cross-resistance between enzalutamide and abiraterone mediated for example by androgen receptor splice variant 7 can be causative. Besides the already approved medications, additional substances are in clinical and preclinical development. Thus, the decision for the best therapeutic sequence becomes more and more difficult. Prospective studies are required to gain more information.