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

Clin Genitourin Cancer. 2014 Feb;12(1):33-40.e4. doi: 10.1016/j.clgc.2013.07.002. Epub 2013 Oct 12.

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.

Patients and 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.

Conclusion: 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.

Keywords: Androgen deprivation therapy; Bone turnover; Prostate cancer; Skeletal-related events.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Amino Acids / urine
  • Androgen Antagonists / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / urine
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects*
  • Denosumab
  • Diphosphonates / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Imidazoles / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy*
  • Orchiectomy
  • Osteocalcin / blood
  • Pamidronate
  • Prognosis
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Zoledronic Acid

Substances

  • Amino Acids
  • Androgen Antagonists
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Osteocalcin
  • Denosumab
  • Zoledronic Acid
  • deoxypyridinoline
  • Alkaline Phosphatase
  • Prostate-Specific Antigen
  • Pamidronate

Associated data

  • ClinicalTrials.gov/NCT00216060