Revisiting the role of bone‐modifying agents in the management of metastatic prostate cancer

Bone metastases are a hallmark of advanced prostate cancer and may drive the morbidity and mortality of the disease in patients with a poor prognosis. The pathogenesis of bone metastasis involves the interaction between cancer cells, normal bone cells and the bone microenvironment. Targeting the bone microenvironment has become a promising therapy for patients with advanced prostate cancer and bone metastasis. This article reviews the use of the antiresorptive bone-targeted agents zoledronic acid and denosumab in the management of skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis. In real-world clinical practice, these agents have been widely prescribed as a concomitant medication to novel mCRPC therapies, such as abiraterone, enzalutamide and radium-223. International guidelines have recommended zoledronic acid or denosumab for the prevention of SREs in patients with bone metastasis from mCRPC. Although there is currently no consensus regarding the optimal sequencing between the bone-targeted agents and novel anti-cancer therapies, future optimal treatments for patients with bone metastasis from prostate cancer may involve the combination of these agents.