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Eur Urol. 2013 Feb;63(2):309-20. doi: 10.1016/j.eururo.2012.10.007. Epub 2012 Nov 23.

New and emerging therapies for bone metastases in genitourinary cancers.

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  • 1Massachusetts General Hospital, Medicine, Division of Hematology-Oncology, 55 Fruit Street, Yawkey 7E, Boston, MA 02114, USA. psaylor@partners.org

Abstract

CONTEXT:

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.

EVIDENCE ACQUISITION:

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.

EVIDENCE SYNTHESIS:

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.

Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PMID:
23201471
[PubMed - indexed for MEDLINE]
PMCID:
PMC3661203
Free PMC Article
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