Metastatic prostate cancer and the bone: significance and therapeutic options

Gartrell, Benjamin A.; Coleman, Robert; Efstathiou, Eleni; Fizazi, Karim; Logothetis, Christopher J.; Smith, Matthew R.; Sonpavde, Guru; Sartor, Oliver; Saad, Fred

doi:10.1016/j.eururo.2015.06.039

Cited by 101Bone health and treatmentsProstate Cancer Treatment and ResearchBone health and osteoporosis research

Metastatic prostate cancer and the bone: significance and therapeutic options

Gartrell, Benjamin A., Coleman, Robert, Efstathiou, Eleni, Fizazi, Karim, Logothetis, Christopher J., Smith, Matthew R., Sonpavde, Guru, Sartor, Oliver +1 more·2015·European Urology

DOI 10.1016/j.eururo.2015.06.039

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Abstract

Context Skeletal involvement is common in metastatic prostate cancer (PCa) and is associated with skeletal-related events (SREs). The interaction of PCa with the bone microenvironment contributes to self-perpetuating progression of cancer in bone. Bone-targeted agents (BTAs) are available for use in metastatic castration-resistant prostate cancer (mCRPC).Objective To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa.Evidence acquisition A literature search was conducted in October 2014. Keywords included clinical trial, prostate cancer, denosumab, bisphosphonates, zoledronic acid, radium-223, bone turnover markers, skeletal-related events, and symptomatic skeletal events.Evidence synthesis The biology of bone metastases in PCa is summarized. Data supporting the use of BTAs in PCa are reviewed, and issues related to the combination and sequencing of available agents are discussed.Conclusions The osteoclast-targeted agents zoledronic acid and denosumab decrease SREs in mCRPC, and the α-emitting radiopharmaceutical agent radium-223 improves survival and decreases symptomatic skeletal events. Limited data are available to guide the sequence and combination of BTAs with disease-modifying agents, although data support the use of osteoclast-targeted drugs with chemotherapy, androgen-targeted agents, and radium-223. Zoledronic acid does not reduce SREs when started prior to castration resistance, although osteoclast-targeted agents do improve outcomes when used in patients with asymptomatic to minimally symptomatic chemotherapy-naive mCRPC. The optimal sequence of radium-223 with chemotherapy is uncertain, although data suggest the efficacy and tolerability of radium-223 is similar with either sequence. Clinical trials evaluating the combination of BTAs with other agents are under way. The optimization of sequence and combination strategies will guide the best use of available agents.Patient summary The literature pertaining to bone metastases in prostate cancer (PCa) was reviewed, and the current understanding of the biology of PCa having spread to bone and the agents available to reduce skeletal complications was discussed.

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Authors: Gartrell, B. A., Coleman, R., Efstathiou, E., Fizazi, K., Logothetis, C. J., Smith, M. R., Sonpavde, G., Sartor, O., & Saad, F.
Affiliations: Albert Einstein College of Medicine (US)
Weston Park Cancer Centre (GB)
National and Kapodistrian University of Athens (GR)
Université Paris-Sud (FR)
Harvard University (US)
University of Alabama at Birmingham Hospital (US)
Tulane University (US)
Corresponding author: Gartrell, Benjamin A.
ORCID: Gartrell, Benjamin A.
Coleman, Robert
Efstathiou, Eleni
Fizazi, Karim
Logothetis, Christopher J.
Smith, Matthew R.
Sonpavde, Guru
Sartor, Oliver
Venue: European Urology
Publisher: Elsevier BV
Published: 2015-11
Volume: 68
Issue: 5
Pages: 850-858
ISSN: 0302-2838 (ISSN-L)
DOI: 10.1016/j.eururo.2015.06.039
OpenAlex: W1930757702
Cited by: 101
References: 53
Citations by year: 2026: 5 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 12 · 2020: 11 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 1
FWCI: 1.04
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Urology (publishedVersion)
PubMed (publishedVersion)
Funders: Bavarian Nordic
Takeda Pharmaceuticals U.S.A.
Janssen Pharmaceuticals
Astellas Pharma US
Sanofi
Bayer Fund
Topics: Health Sciences › Medicine › Oncology › Bone health and treatments
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: metastatic prostate cancer, bone metastasis, skeletal-related events, bone-targeted agents, castration-resistant prostate cancer, denosumab, zoledronic acid, bisphosphonates, radium-223, bone microenvironment, treatment sequencing, combination therapy, bone turnover markers
MeSH terms: Denosumab, Zoledronic Acid, Bone Neoplasms, Diphosphonates, Fractures, Spontaneous, Humans, Imidazoles, Male, Prostatic Neoplasms, Radioisotopes, Radium, Bone Density Conservation Agents

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Metastatic prostate cancer and the bone: significance and therapeutic options

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