title: Response in bone turnover markers during therapy predicts overall survival in patients with metastatic prostate cancer: analysis of three clinical trials.
abstract: BACKGROUND
  The bone-forming metastases of prostate cancer result from complex stromal-epithelial interactions within the tumour microenvironment. Autocrine-paracrine signalling pathways between prostate cancer epithelial cells, osteoblasts, and osteoclasts stimulate aberrant bone remodelling, and the activity of these three cell populations can be quantitatively measured using prostate-specific antigen (PSA), bone-specific alkaline phosphatase (BAP) and urine N-telopeptide (uNTx), respectively. The purpose of the present study was to test the hypothesis that serial measurements of BAP and uNTx during therapy would facilitate monitoring of disease activity and predict the overall survival (OS) in patients with metastatic prostate cancer receiving therapy.
  
  
  METHODS
  Radionuclide bone scan, PSA, BAP, and uNTx data were retrospectively analysed from three clinical trials in patients with metastatic prostate cancer conducted at our institution. Qualitative changes in bone scans and quantitative changes in PSA, BAP, and uNTx concentrations during therapy were correlated with OS.
  
  
  RESULTS
  Baseline levels of BAP, but not PSA, were prognostic for OS in both androgen-dependent and castrate-resistant disease. A reduction in PSA, BAP, uNTx, or BAP/uNTx on therapy was predictive of improved OS in both patient groups. Conversely, an increase in PSA, or BAP on therapy was predictive of worse OS in both patient groups. Baseline number of lesions and response on bone scan during therapy were neither prognostic nor predictive of OS in either patient group.
  
  
  CONCLUSIONS
  These observations support the concept that serial measurements of bone turnover metabolites during therapy function as clinically informative predictive biomarkers in patients with advanced prostate cancer and skeletal metastases. PSA measurements and bone scans remain essential to monitor the overall disease activity and determine the anatomic distribution of skeletal metastases.
authors.affiliation: Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Houston, TX 77230, USA.
authors.forename: A
authors.initials: A
authors.lastname: Som
authors.forename: S-M
authors.initials: SM
authors.lastname: Tu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Qiao
authors.forename: C
authors.initials: C
authors.lastname: Logothetis
authors.forename: P G
authors.initials: PG
authors.lastname: Corn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000032:analysis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000652:urine; D006801:Humans; D007610:Kallikreins / Q000032:analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010455:Peptides / Q000652:urine; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen