Metastatic Prostate Cancer and the Bone: Significance and Therapeutic Options

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)

To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa

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

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

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

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

European urology 2015 Jul 04 [Epub ahead of print]

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

Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Electronic address: bgartrel@montefiore org , Academic Unit of Clinical Oncology, Weston Park Hospital, CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK , Department of Genitourinary Medical Oncology, Stanford Alexander Tissue Derivatives Laboratory, David H Koch Center for Applied Research of Genitourinary Cancers, Houston, TX, USA; Department of Clinical Therapeutics, University of Athens, Athens, Greece , Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France , Department of Genitourinary Medical Oncology, Stanford Alexander Tissue Derivatives Laboratory, David H Koch Center for Applied Research of Genitourinary Cancers, Houston, TX, USA , Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA , Department of Internal Medicine, Section of Medical Oncology, UAB Medical Center, Birmingham, AL, USA , Department of Medicine and Urology, Tulane University, New Orleans, LA, USA , Centre Hospitalier de I'Université de Montréal, Montreal, Quebec, Canada



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