title: New and emerging therapies for bone metastases in genitourinary cancers.
abstract: BACKGROUND
  Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality.
  
  
  OBJECTIVE
  The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies.
  
  
  METHODS
  We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial data focus on prostate cancer (PCa). We provide a nonsystematic review and our perspective on the available data.
  
  
  RESULTS
  Clinical manifestations can include pain, hypercalcemia, pathologic fractures, and spinal cord compression. Optimal systemic therapy for skeletal metastases often features a combination of disease-specific therapy and bone-targeted therapy. Some agents, such as the radiopharmaceutical radium-223, blur the line between those categories. Osteoclast inhibition is a validated strategy in the management of selected patients with bone metastases. Zoledronic acid, a bisphosphonate, is approved for the prevention of skeletal events caused by solid tumors metastatic to bone. Denosumab is a fully human monoclonal antibody that inactivates receptor activator of nuclear factor-κB ligand and is approved for the same indication. Beta-emitting radiopharmaceuticals can be effective for the palliation of pain caused by bone metastases, but their use is often limited by marrow suppression. The alpha-emitting radiopharmaceutical radium-223 has recently been shown to improve overall survival and prevent skeletal events in select men with castration-resistant PCa metastatic to bone. Multiple ongoing clinical trials are designed to examine the potential for therapeutic inhibition of additional targets such as Src and hepatocyte growth factor (MET).
  
  
  CONCLUSIONS
  Bone metastases cause considerable morbidity and mortality among patients with genitourinary malignancies. Optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. Further research is needed to optimize the use of existing agents and to define the therapeutic potential of novel targets.
authors.affiliation: Massachusetts General Hospital, Medicine, Division of Hematology-Oncology, 55 Fruit Street, Yawkey 7E, Boston, MA 02114, USA. psaylor@partners.org
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Saylor
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.forename: Stephen
authors.initials: S
authors.lastname: Freedland
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pienta
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy*; D002277:Carcinoma / Q000556:secondary* / Q000628:therapy*; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000473:pathology; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D014565:Urogenital Neoplasms / Q000473:pathology*; D019459:Urothelium; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; D019275:Radiopharmaceuticals; D000069448:Denosumab; D000077211:Zoledronic Acid; D011883:Radium