title: Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  We have recently witnessed a rapid increase in the number of effective systemic agents for men with metastatic castration-resistant prostate cancer (CRPC), including novel hormonal therapies (abiraterone acetate and MDV3100), immunotherapies (sipuleucel-T), chemotherapies (cabazitaxel), and bone microenvironment targeting agents (denosumab, radium 223). Given the increasing complexity of treatment decisions for this disease, major research and clinical priorities are (1) finding biomarkers that enable an understanding of the natural history and complex biology of this heterogeneous malignancy, (2) defining predictive biomarkers that identify men most likely to benefit from a given therapy, and (3) identifying biomarkers of early response or progression to optimize outcomes.
  
  
  OBJECTIVE
  In this review, we discuss existing and potential biomarkers in CRPC and how they may currently inform prognosis, aid in treatment selection (predictive value), and relate to survival outcomes (surrogacy).
  
  
  METHODS
  PubMed-based literature searches and abstracts through September 2011 provided the basis for this literature review as well as expert opinion.
  
  
  RESULTS
  We address blood and urine-based biomarkers such as prostate-specific antigen, lactate dehydrogenase, total and bone alkaline phosphatase and other bone turnover markers, hemoglobin, and circulating tumor cells in the context of prognosis, prediction, and patient selection for therapy. Given the inherent problems associated with defining progression-free survival in CRPC, the importance of biomarker development and the needed steps are highlighted. We place the discussion of biomarkers within the context of the design/intent of a trial and mechanism of action of a given systemic therapy. We discuss novel biomarker development and the pathway for surrogate or predictive biomarkers to become credentialed as useful tests that inform therapeutic decisions.
  
  
  CONCLUSIONS
  A greater understanding of biomarkers in CRPC permits a more personalized approach to care that maximizes benefit and minimizes harm and can inform clinical trials tailored to men most likely to derive benefit.
authors.affiliation: Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, NC 27710, USA. andrew.armstrong@duke.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: A Oliver
authors.initials: AO
authors.lastname: Sartor
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000740:Anemia / Q000503:physiopathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009360:Neoplastic Cells, Circulating; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery*; D014020:Tissue Extracts / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D014020:Tissue Extracts; C511774:sipuleucel-T; D007770:L-Lactate Dehydrogenase; D017430:Prostate-Specific Antigen
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