Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

SIMPLE SUMMARY: Over the disease course of metastatic prostate cancer, approximately the 90% of patients develops bone metastases, with bone involvement frequently leading to various skeletal complications including pathological fractures, spinal cord compression, and pain. Notably enough, the peculiar inclination of prostate cancer cells to seed the bone is considered an important cause of morbidity for prostate cancer patients. Recent years have witnessed the advent of several novel treatments for prostate cancer, and therapeutic paradigms are rapidly shifting. In this review, we aim at giving an overview of current knowledge on the relationship between prostate cancer and bone, especially focusing on the use of bone-targeted agents in this setting. ABSTRACT: Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.