OCT 16, 2013 07:00 AM PDT

Prognostic, predictive, and surrogate biomarkers in men with castration resistant metastatic prostate cancer

  • Associate Professor of Medicine and Surgery, Duke Cancer Institute, Divisions of Medical Oncology and Urology, Duke University
      Andrew J. Armstrong, MD, ScM, is co-program leader of the genitourinary oncology research program, part of the oncology clinical trials shared resource of the Duke Comprehensive Cancer Center. Armstrong is an internationally recognized expert in prostate cancer outcomes studies in men with castration-resistant metastatic disease, including nomograms and risk group models on prognosis. His research is focused on the development of experimental therapeutics in advanced prostate cancer, particularly those targeting the PI3 kinase/mTOR pathways, as well as the development of prognostic and predictive biomarkers of treatment efficacy, particularly with a focus on circulating tumor cell biology and epithelial-mesenchymal transition (epithelial plasticity). Armstrong is the principal investigator on four investigator-initiated clinical trials and approximately 10 industry or cooperative group sponsored clinical trials, as well as several correlative science studies. In addition to co-directing a clinical research program in genitourinary malignancies, Armstrong serves on the Duke IRB and cancer protocol committee, and is an active member of the Duke Comprehensive Cancer Centers editorial advisory and fellowship committees, and serves as the editor of the Duke Prostate Center newsletter [link]. Armstrongs laboratory collaborates with the laboratory of Mariano Garcia-Blanco, MD, PhD, a renowned RNA biologist, to study alternative RNA splicing as it applies to prostate cancer metastasis and EMT. After completing his fellowship in medical oncology at Johns Hopkins in 2006, Armstrong received his masters of science in clinical investigation from the Johns Hopkins Bloomberg School of Public Health in 2008. Armstrong is a recipient of a Prostate Cancer Foundation Young Investigator Award (2008-2011), an American Society of Clinical Oncology Young Investigator Award (2005-2008), an American Association for Cancer Research Clinical and Translational Fellowship (2005-2008), and has received a Department of Defense Prostate Cancer Research Program Physician Research Training Award (2010-2015). He serves on the National Comprehensive Cancer Center's prostate cancer guidelines panel. Armstrong has published extensively on prostate cancer experimental therapies and prognostic models, including peer reviewed articles, reviews, and numerous book chapters and abstracts.


    With the rapid rise in the number of therapeutic options for men with castration-resistant prostate cancer (CRPC) comes increasingly complicated treatment decision-making, emphasizing the need for biomarkers that can identify appropriate patients for specific treatments and accurately assess benefit. While prognostic factors describe natural history, predictive biomarkers are factors related to the disease or the host that are associated with improvements in outcomes, such as survival, due to specific therapies. Surrogate biomarkers provide an early estimate of treatment effect as an intermediate endpoint for outcomes such as survival. Such biomarkers have become of increasing importance in oncology to maximize the benefits of novel systemic agents while minimizing the harms to individual patients and the costs to society. Given the number of newly approved and expensive systemic therapies, including novel hormonal therapies, chemotherapies, immunotherapies, and bone microenvironment-targeting therapies, predictive biomarkers are needed to give physicians a more rational sense of matching the right patient to the right therapy sequence at a given time. Here I discuss prognostic and potential predictive biomarkers in men with CRPC and discuss their potential role in the management of men with metastatic disease. Learning objectives: 1. Define prognostic and predictive biomarkers and apply this knowledge to metastatic prostate cancer patients based on established biomarkers in the castration-resistant setting. 2. Understand the role of surrogate biomarkers in drug development, particularly with respect to metastatic prostate cancer.

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