title: Serum procollagen 1 amino-terminal propeptide (P1NP) in prostate cancer: pitfalls of its use as an early surrogate marker for bone metastasis.
abstract: BACKGROUND
  Procollagen 1 amino-terminal propeptide (P1NP) is a bone formation marker and has been shown to have a strong association with the extent of bone metastases (BM) in patients with advanced prostate cancer. More recently, its levels were found to be affected by androgen deprivation therapies and bisphosphonates. We investigated the role of P1NP as a surrogate marker of sub-radiological skeletal metastases in prostate cancer patients with biochemical failure (BF).
  
  
  METHODS
  BePrepared is a prospective longitudinal substudy of RADAR trial in which serial P1NPs were collected at regular intervals for 123 patients who had completed RADAR protocol treatment.
  
  
  RESULTS
  There was no trend identified in P1NP levels prior to diagnosis of BM. We found that there was no difference in P1NP concentrations at the time of diagnosis of BM in the group that developed BM compared with P1NP levels in groups with only nodal metastases or BF. In the group of patients who did not experience BF, P1NP was affected by previous luteinizing hormone-releasing hormone-agonist and bisphosphonate therapy. Hence, patients who received an 18-month course of androgen deprivation without bisphosphonates had significantly higher P1NP values than patients with shorter androgen deprivation therapy (ADT) course combined with a course of bisphosphonates.
  
  
  CONCLUSIONS
  P1NP is not a sensitive serum marker of early BM in high-risk prostate cancer patients with BF and low prostate-specific antigen levels as its levels are affected by prior history of bone remodelling therapies such as ADT and bisphosphonates.
authors.affiliation: Department of Radiation Oncology, Calvary Mater Hospital, Waratah, Australia.
authors.forename: Eka
authors.initials: E
authors.lastname: Moseshvili
authors.forename: David J
authors.initials: DJ
authors.lastname: Joseph
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Cohen
authors.forename: Alberta
authors.initials: A
authors.lastname: Abreu
authors.forename: Allison
authors.initials: A
authors.lastname: Kautto
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000097:blood* / Q000401:mortality / Q000556:secondary*; D004164:Diphosphonates / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D055088:Early Detection of Cancer / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood*; D015995:Prevalence; D011347:Procollagen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D000077211:Zoledronic Acid; D016729:Leuprolide
keywords: biochemical failure; biomarker; procollagen 1 amino-terminal propeptide (P1NP); prostate cancer