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  • Review Article
  • Published:

Managing bone metastases and reducing skeletal related events in prostate cancer

Nature Reviews Clinical Oncology volume 11, pages 335–345 (2014)Cite this article

Subjects

A Corrigendum to this article was published on 11 November 2014

This article has been updated

Key Points

  • Metastatic castration-resistant prostate cancer (mCRPC) is associated with complications in bone known as skeletal-related events (SREs) that are associated with decreased quality of life and increased mortality

  • Androgen-deprivation therapy is used to treat advanced-stage prostate cancer and leads to loss of bone mineral density (BMD) and increases the risk of fracture

  • Osteoclast-targeted agents including the bisphosphonate zoledronic acid and the monoclonal antibody denosumab are used to reduce the incidence of SREs and to decrease loss of BMD

  • A number of recently approved agents including androgen pathway inhibitors abiraterone and enzalutamide and the radiopharmaceutical radium-223 have been shown to increase survival and to decrease skeletal morbidity in mCRPC

  • Cabozantinib, a multi-targeted tyrosine kinase inhibitor, is an agent in development that has demonstrated promising activity in CRPC metastatic to bone

Abstract

Advanced-stage prostate cancer is associated with skeletal complications related to metastatic disease and its treatment. On the one hand, metastatic disease to bone is commonly associated with skeletal-related events (SREs); on the other hand, treatment with androgen-deprivation therapy (ADT) leads to loss in bone mineral density (BMD) and increased risk of fracture. Despite osteoblastic appearance on radiography, bone metastases from prostate cancer are associated with increased osteoblast and osteoclast activity providing the rationale for treatment with osteoclast-targeted agents. The bisphosphonate zoledronic acid and the monoclonal antibody denosumab reduce the incidence of SREs in metastatic castration-resistant prostate cancer (mCRPC). A number of agents prevent loss of BMD associated with ADT, but only denosumab is approved to reduce fractures in patients with non-metastatic prostate cancer. Another recently approved agent—radium-223—improves survival and delays SREs in mCRPC. The inhibitors of androgen receptor signalling, abiraterone and enzalutamide, improve survival in mCRPC and delay SREs, although the latter is likely related to control of disease rather than a direct effect on bone. Finally, the tyrosine kinase inhibitor cabozantinib shows promising activity in bone metastases from mCRPC. This Review addresses the skeletal morbidity associated with prostate cancer and the therapeutic options that exist to treat it.

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Figure 1: The 'vicious cycle' of bone metastases.
Figure 2: Bone-targeted agents and their respective targets.

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Change history

  • 11 November 2014

    In the version of this manuscript originally published online and in print, some data in Table 1 were incorrect. These errors have now been corrected in the online HTML and PDF versions of the manuscript.

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    Benjamin A. Gartrell

  2. Centre Hospitalier de I'Université de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke East, Montreal, H2L 4M1, QC, Canada

    Fred Saad

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Gartrell, B., Saad, F. Managing bone metastases and reducing skeletal related events in prostate cancer. Nat Rev Clin Oncol 11, 335–345 (2014). https://doi.org/10.1038/nrclinonc.2014.70

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