ABSTRACT

Bone metastasis are a common condition of castration resistant prostate cancer (CRPC) and a major cause of morbidity, mortality and increased treatment costs. They are associated skeletalrelated events (SREs), including pathologic fracture, spinal cord compression, and the need for surgery or external radiotherapy to the bone. Also, androjen deprivation therapy (ADT) for prostate cancer leads to accelareted bone loss and associated with fragility fractures. In this manner, optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. RANK ligand (RANKL) is an important mediator of bone resorption. Denosumab is a fully human monoclonal antibody that binds avidly and specifically to RANKL, inactivating it. It has been showed that inhibition of RANKL/RANK pathway with denosumab can delay bone metastasis and SREs. Denosumab is currently avaible for clinical use. Radium-223 is an experimental, alpha-emitting, calcium mimetic and thus a natural bone-seeking agent. In a phase III trial (ALSYMPCA), Radium-223 treatment resulted in improved overall survival and delayed SREs. Adverse events consist of minor gastrointestinal side effects and mild myelosupression that were rarely severe. Denosumab and Radium-223 may represent unique and distinct options for patients with CRPC; future trials should address their use in combination or in sequence with existing and novel agents.