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  • Review Article
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Targeting bone metastases in prostate cancer: improving clinical outcome

Nature Reviews Urology volume 12, pages 340–356 (2015)Cite this article

Subjects

Key Points

  • Bone metastases are common in metastatic castration-resistant prostate cancer (mCRPC) and lead to skeletal-related events (SREs), which are a major cause of patient disability, reduced quality of life, and death

  • Understanding the pathophysiology of bone metastasis resulted in the approval of agents that improve clinical outcomes in patients with mCRPC, and new targeted agents are under development in this setting

  • Managing both the tumour and associated SREs is important to improve survival and quality of life of patients with mCRPC

  • Osteoclast inhibitors are part of the standard treatment of CRPC metastatic to bone; denosumab has been shown to reduce skeletal morbidity more than zoledronic acid

  • New antitumour agents increase survival and some, such as abiraterone and enzalutamide and 223Ra, also decrease skeletal morbidity

  • Ongoing clinical studies are investigating the optimal position and combinations of approved agents in the treatment paradigm to maximize patient benefit in this setting

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.

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Figure 1: The cyclic feedback loop between PCBMs, osteoblasts and osteoclasts, and target sites of therapeutics.

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Acknowledgements

The authors would like to express their gratitude to Dr P. Hoban (Cancer Communications & Consultancy Ltd, Knutsford, UK) for providing writing assistance funded by Bayer Consumer Care AG.

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Authors and Affiliations

  1. Department of Medicine, Department of Medicine, CHU Brugmann, Place Van Gehuchten, 1020, Brussels, Belgium

    Jean-Jacques Body

  2. Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Sandra Casimiro & Luís Costa

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  1. Jean-Jacques Body
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  2. Sandra Casimiro
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All authors were involved in researching data for the article, made substantial contributions to discussion of its content and were involved in writing and review/editing of the manuscript before submission.

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Correspondence to Jean-Jacques Body.

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Competing interests

J.J.B. has received speaker's fees from Amgen and consulting fees from Amgen and Bayer. L.C. has received research funding and speaker's fees from Amgen, Novartis, and Roche. S.C. declares no competing interests.

Supplementary information

Supplementary Table 1

Summary of efficacy data from randomised trials of bone targeting-agents approved in mCRPC (PDF 166 kb)

Supplementary Table 2

Selected studies of Ra-223 in mCRPC with bone metastases (PDF 105 kb)

Supplementary Table 3

Summary of efficacy data of antineoplastic agents approved for patients with CRPC with bone metastases (PDF 160 kb)

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Body, JJ., Casimiro, S. & Costa, L. Targeting bone metastases in prostate cancer: improving clinical outcome. Nat Rev Urol 12, 340–356 (2015). https://doi.org/10.1038/nrurol.2015.90

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