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Markers of Bone Metabolism and Survival in Men with Hormone-Refractory Metastatic Prostate Cancer

Authors' Affiliations: ¹ Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada; ² Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom; ³ Milton S. Hershey Medical Center, Hershey, Pennsylvania; ⁴ Hamilton Regional Cancer Center and Department of Medicine, McMaster University, Hamilton, Ontario, Canada; ⁵ Novartis Pharmaceuticals Corp., East Hanover, New Jersey; ⁶ Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montreal, Quebec, Canada; and ⁷ Massachusetts General Hospital, Boston, Massachusetts

Requests for reprints: Matthew R. Smith, Massachusetts General Hospital, Cox 640, 100 Blossom Street, Boston, MA 02114. Phone: 617-724-5257; Fax: 617-726-4899; E-mail: smith.matthew{at}mgh.harvard.edu.

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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