Denosumab: a new option in the treatment of bone metastases from urological cancers

Takeshi Yuasa, Shinya Yamamoto, Shinji Urakami, Iwao Fukui, Junji Yonese

Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan

Abstract: Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA), a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers.

Keywords: bone metastasis, denosumab, prostate cancer, renal cell cancer, urothelial cancer, zoledronic acid