Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer

Richard J. Cook, Robert Coleman, Janet Brown, Allan Lipton, Pierre Major, Yong Jiang Hei, Fred Saad, Matthew R. Smith

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. Results: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP. Conclusions: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.

Original languageEnglish (US)
Pages (from-to)3361-3367
Number of pages7
JournalClinical Cancer Research
Volume12
Issue number11 I
DOIs
StatePublished - Jun 1 2006

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Alkaline Phosphatase
Prostatic Neoplasms
Hormones
Bone and Bones
Survival
Serum
zoledronic acid
Osteoclasts
Prostate-Specific Antigen
Osteoblasts
L-Lactate Dehydrogenase
Analgesics
Hemoglobins
Neoplasm Metastasis
Bone Neoplasms
Bone Diseases
Castration
collagen type I trimeric cross-linked peptide
Proportional Hazards Models
Androgens

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cook, Richard J. ; Coleman, Robert ; Brown, Janet ; Lipton, Allan ; Major, Pierre ; Hei, Yong Jiang ; Saad, Fred ; Smith, Matthew R. / Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 11 I. pp. 3361-3367.
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abstract = "Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. Results: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95{\%} confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP. Conclusions: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.",
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Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. / Cook, Richard J.; Coleman, Robert; Brown, Janet; Lipton, Allan; Major, Pierre; Hei, Yong Jiang; Saad, Fred; Smith, Matthew R.

In: Clinical Cancer Research, Vol. 12, No. 11 I, 01.06.2006, p. 3361-3367.

Research output: Contribution to journalArticle

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T1 - Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer

AU - Cook, Richard J.

AU - Coleman, Robert

AU - Brown, Janet

AU - Lipton, Allan

AU - Major, Pierre

AU - Hei, Yong Jiang

AU - Saad, Fred

AU - Smith, Matthew R.

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N2 - Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. Results: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP. Conclusions: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.

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