title: Failure to suppress markers of bone turnover on first-line hormone therapy for metastatic prostate cancer is associated with shorter time to skeletal-related event.
abstract: BACKGROUND
  Elevated markers of bone turnover are prognostic for shorter survival in castration-resistant prostate cancer. We aimed to determine the prognostic value of bone turnover markers in metastatic hormone-sensitive prostate cancer.
  
  
  METHODS
  Markers of bone turnover (urine deoxypyridinoline [DPD] and N-telopeptide, serum bone alkaline phosphatase (AP), and osteocalcin [OC]) from baseline and after 6 months of study were assessed in men enrolled in a prospective metastatic prostate cancer trial with androgen deprivation therapy (ADT) with or without risedronate (ClinicalTrials.gov, NCT00216060).
  
  
  RESULTS
  Serum samples were collected from 63 patients with bone involvement and a median follow-up of 39.7 months. A multivariate model using Cox regression-which included prostate-specific antigen (PSA) nadir, bisphosphonate treatment, and extent of metastases-showed that suppression of bone turnover markers after 6 months of therapy compared with baseline was significantly associated with longer skeletal-related event (SRE)-free survival. ADT without bisphosphonate therapy was also associated with a decline in markers of bone turnover, presumably resulting from direct anticancer activity. Elevated baseline bone turnover markers were not prognostic.
  
  
  CONCLUSIONS
  Failure to suppress bone turnover while receiving ADT, even when otherwise responding to therapy, may identify patients with hormone-sensitive metastatic prostate cancer who are destined for a shorter time to SREs and progression.
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.affiliation: Hoosier Oncology Group, Indianapolis, IN.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kirkpatrick
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School Boston, MA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School Boston, MA. Electronic address: christopher_sweeney@dfci.harvard.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000726:Androgen Antagonists / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009919:Orchiectomy; D015675:Osteocalcin / Q000097:blood; D000077268:Pamidronate; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D000077211:Zoledronic Acid
chemical_list: D000596:Amino Acids; D000726:Androgen Antagonists; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D015675:Osteocalcin; D000069448:Denosumab; D000077211:Zoledronic Acid; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D000077268:Pamidronate
keywords: Androgen deprivation therapy; Bone turnover; Prostate cancer; Skeletal-related events