title: Targeting bone metastases in prostate cancer: improving clinical outcome.
abstract: Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development.
authors.affiliation: Department of Medicine, CHU Brugmann, Department of Medicine, Place Van Gehuchten, 1020 Brussels, Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Body
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Casimiro
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Costa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000556:secondary*; D000069448:Denosumab / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D010006:Osteoblasts / Q000502:physiology; D010014:Osteolysis; D010146:Pain / Q000503:physiopathology; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality* / Q000473:pathology*; D011788:Quality of Life; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D011883:Radium / Q000627:therapeutic use; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D000069448:Denosumab; D000077211:Zoledronic Acid; C581106:radium Ra 223 dichloride; D011883:Radium