Bisphosphonates: prevention of bone metastases in prostate cancer.

Bone metastases and their associated morbidities are common in patients with advanced prostate cancer and other genitourinary (GU) malignancies. Zoledronic acid> (a bisphosphonate) has long been the mainstay of treatment for reducing the risk of skeletal-related events in patients with bone metastases from GU cancers, and denosumab (a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand [RANKL]) has recently received approval for this indication in the United States. Preclinical data indicate that modifying the bone microenvironment may render it less conducive to metastasis, and emerging clinical findings suggest that the potential benefits from bone-directed therapies are not limited to reducing skeletal morbidity-these agents might help to improve survival and delay bone disease progression or even development of bone metastases (if used earlier in the disease course). This chapter reviews the rationale and recent clinical data supporting an antimetastatic role for bone-directed therapies in patients with GU malignancies.