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

• Published in: Clinical cancer research Vol. 12; no. 11; pp. 3361 - 3367
• Main Authors: Cook, Richard J., Coleman, Robert, Brown, Janet, Lipton, Allan, Major, Pierre, Hei, Yong Jiang, Saad, Fred, Smith, Matthew R.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2006
• Subjects: Aged; Alkaline Phosphatase - blood; Antineoplastic agents; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - urine; bone metastases; Bone Neoplasms - diagnosis; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Diphosphonates - therapeutic use; Disease Progression; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Imidazoles - therapeutic use; Male; Male genital diseases; Medical sciences; Multicenter Studies as Topic - statistics & numerical data; Multivariate Analysis; Nephrology. Urinary tract diseases; osteoblast; osteoclast; Peptides - urine; Pharmacology. Drug treatments; Prognosis; Proportional Hazards Models; prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Randomized Controlled Trials as Topic - statistics & numerical data; survival; Survival Rate; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Treatment resistance; Urinary system disease; Prostate disease; Hormone therapy; Biological marker; Male; Malignant tumor; Metastasis; Metabolism; Survival; Osteoarticular system; Adult; Advanced stage; Bone; Pharmacokinetics; Male genital diseases; Prostate cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-0269

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.