ABSTRACT

Bone metastasis is a common condition in advanced prostate cancer and is the biggest cause of morbidity, mortality, and increased cost of treatment. Therefore, preventing skeletal-related events (SREs) in this patient group is important. For this purpose, denosumab, alpha and beta emitting radioisotopes and proteasome inhibitors are the current agents and many treatment options are being developed. Alpharadin is a radium-223 α-emitter, which is a bone specific agent. Beyond overall survival benefit, significant palliative effect of an α-emitting radioisotope, radium-233 has been shown in patients with painful bone metastases. Denosumab, a monoclonal human antibody, is driven osteoclast formation, function, and survival-related key mediator RANKL (receptor activator of nuclear factor- κB ligand). Denosumab has been shown to reduce the incidence of vertebral fractures and increase total hip, femoral neck and lumbar spine bone mineral density in patients receiving androgen deprivation therapy (ADT) with non-metastatic disease. Proteasome inhibition has anabolic effects on bone directly. In multiple myeloma, bortezomib, the first-in-class proteasome inhibitor, has shown both in vitro and in vivo regulation of bone remodeling by inhibiting osteoclast function and promoting osteoblast activity. Systemic radiotherapy applied with two radioisotopes named strontium-89 and samarium-153 is highly effective in the palliation of pain. Over the last decade, rapid development of new treatment options has been seen with a better understanding of the metastatic castration-resistant prostate cancer (mCRPC) biology. Orteronel, tasquinomod, prostvac, custirsen and cabozantinib are some of the agents have been studied in order to increase pain palliation, reduce side effects and prolong survival.