[Sequencing and combination of agents in castration resistant prostate cancer.]

Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet.

The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient.

A literature review was performed through Medline Database (Pubmed) using as key words: "Castrate Resistant Prostate Cancer", "Sequencing", "Biomarkers", "Systemic Therapy". We also reviewed ASCO GU 2017 abstracts.

Since Docetaxel was approved in 2004, which increased overall survival by about 2 months in patients with Metastatic Castration Resistant Prostate Cancer, in recent years a large number of therapies have been approved, demonstrating an increase in overall survival after several phase III clinical trials: Cabacitaxel, Abiraterone, Enzalutamide, Sipuleucel-T, Denosumab, Radium 223. And more recently, some investigations about new targeted therapies directed to the androgen receptor, with greater affinity than enzalutamide, or more accurate inhibitors of CYP 17 enzyme than abiraterone, as well as, agents as monoclonal antibodies (anti PD1), vaccines, poly adenosine diphosphate- ribose polymerase inhibitors, are coming to the light. In the future, these outcomes could tune up the treatment sequencing, through the study of predictive biomarkers that will indicate the right target of each therapy.

In the near future, outcomes of different clinical trials that are studying new molecules, will allow us to apply the sequencing of different therapies based on biomarkers present in blood (circulating tumor cells) or in specimen biopsies, achieving an increase in overall survival and improving quality of life of patients in the advanced stage of the disease, however the best choice of sequence is unknown at this moment.