Metastatic prostate cancer and the bone

Significance and therapeutic options

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)850-858
Number of pages9
JournalEuropean Urology
Volume68
Issue number5
DOIs
StatePublished - Nov 1 2015

Fingerprint

Bone Neoplasms
Prostatic Neoplasms
zoledronic acid
Radium
Bone and Bones
Castration
Osteoclasts
Therapeutics
Clinical Trials
Neoplasm Metastasis
Drug Therapy
Radiopharmaceuticals
Bone Remodeling
Diphosphonates
Androgens

Keywords

  • Bone metastases
  • Bone-targeted agents
  • Prostate cancer
  • Skeletal-related events
  • Symptomatic skeletal events

ASJC Scopus subject areas

  • Urology

Cite this

Gartrell, B. A., Coleman, R., Efstathiou, E., Fizazi, K., Logothetis, C. J., Smith, M. R., ... Saad, F. (2015). Metastatic prostate cancer and the bone: Significance and therapeutic options. European Urology, 68(5), 850-858. https://doi.org/10.1016/j.eururo.2015.06.039

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.

In: European Urology, Vol. 68, No. 5, 01.11.2015, p. 850-858.

Research output: Contribution to journalArticle

Gartrell, BA, Coleman, R, Efstathiou, E, Fizazi, K, Logothetis, CJ, Smith, MR, Sonpavde, G, Sartor, O & Saad, F 2015, 'Metastatic prostate cancer and the bone: Significance and therapeutic options', European Urology, vol. 68, no. 5, pp. 850-858. https://doi.org/10.1016/j.eururo.2015.06.039
Gartrell, Benjamin A. ; Coleman, Robert ; Efstathiou, Eleni ; Fizazi, Karim ; Logothetis, Christopher J. ; Smith, Matthew R. ; Sonpavde, Guru ; Sartor, Oliver ; Saad, Fred. / Metastatic prostate cancer and the bone : Significance and therapeutic options. In: European Urology. 2015 ; Vol. 68, No. 5. pp. 850-858.
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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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N2 - 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.

AB - 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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