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Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors.
J Natl Cancer Inst. 2005 Jan 05; 97(1):59-69.JNCI

Abstract

BACKGROUND

Whether bone markers have prognostic value in patients with bone metastases is unknown. We investigated this question in patients with bone metastases secondary to prostate cancer and to non-small-cell lung cancer (NSCLC) and other solid tumors assigned to the placebo arms of two phase III trials of zoledronic acid.

METHODS

Levels of the urinary bone resorption marker N-telopeptide and the serum bone formation marker bone-specific alkaline phosphatase were assessed every 3 months for patients with prostate cancer (n = 203) or NSCLC or other solid tumors (n = 238) and were categorized as low or high. Patients were monitored for skeletal-related events, bone disease progression, and death. The relative risks (RRs) and 95% confidence intervals (CIs) for these outcomes were estimated for patients with high versus low levels of each marker using intensity-based multiple event and Cox regression models. All statistical tests were two-sided.

RESULTS

In each disease group and overall, high levels of each marker at the beginning of the study were statistically significantly associated with an increased risk of negative outcomes. Use of recent marker assessments as time-dependent covariates gave even greater prognostic significance. High N-telopeptide levels were a stronger prognostic indicator of negative outcomes than bone-specific alkaline phosphatase levels. In recent assessments, patients with high N-telopeptide levels had an increased relative risk of skeletal-related events (prostate cancer, RR = 3.25, 95% CI = 2.26 to 4.68, P<.001; NSCLC and other solid tumors, RR = 1.79, 95% CI = 1.15 to 2.79, P = .010), disease progression (prostate cancer, RR = 2.02, 95% CI = 1.48 to 2.74, P<.001; NSCLC and other solid tumors, RR = 1.91, 95% CI = 1.16 to 3.15, P = .011), and death (prostate cancer, RR = 4.59, 95% CI = 2.82 to 7.46, P<.001; NSCLC and other solid tumors, RR = 2.67, 95% CI = 1.85 to 3.85, P<.001) compared with patients with low N-telopeptide levels.

CONCLUSIONS

Baseline and recent bone marker levels were predictive of negative clinical outcomes in patients with bone metastases secondary to prostate cancer and to NSCLC and other solid tumors. N-telopeptide levels were more consistent prognostic indicators than bone-specific alkaline phosphatase for all tumor types, reflecting the key role of osteolysis in the development of skeletal complications.

Authors+Show Affiliations

Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield, England, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15632381

Citation

Brown, Janet E., et al. "Bone Turnover Markers as Predictors of Skeletal Complications in Prostate Cancer, Lung Cancer, and Other Solid Tumors." Journal of the National Cancer Institute, vol. 97, no. 1, 2005, pp. 59-69.
Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005;97(1):59-69.
Brown, J. E., Cook, R. J., Major, P., Lipton, A., Saad, F., Smith, M., Lee, K. A., Zheng, M., Hei, Y. J., & Coleman, R. E. (2005). Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. Journal of the National Cancer Institute, 97(1), 59-69.
Brown JE, et al. Bone Turnover Markers as Predictors of Skeletal Complications in Prostate Cancer, Lung Cancer, and Other Solid Tumors. J Natl Cancer Inst. 2005 Jan 5;97(1):59-69. PubMed PMID: 15632381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. AU - Brown,Janet E, AU - Cook,Richard J, AU - Major,Pierre, AU - Lipton,Allan, AU - Saad,Fred, AU - Smith,Matthew, AU - Lee,Ker-Ai, AU - Zheng,Ming, AU - Hei,Yong-Jiang, AU - Coleman,Robert E, PY - 2005/1/6/pubmed PY - 2005/1/22/medline PY - 2005/1/6/entrez SP - 59 EP - 69 JF - Journal of the National Cancer Institute JO - J Natl Cancer Inst VL - 97 IS - 1 N2 - BACKGROUND: Whether bone markers have prognostic value in patients with bone metastases is unknown. We investigated this question in patients with bone metastases secondary to prostate cancer and to non-small-cell lung cancer (NSCLC) and other solid tumors assigned to the placebo arms of two phase III trials of zoledronic acid. METHODS: Levels of the urinary bone resorption marker N-telopeptide and the serum bone formation marker bone-specific alkaline phosphatase were assessed every 3 months for patients with prostate cancer (n = 203) or NSCLC or other solid tumors (n = 238) and were categorized as low or high. Patients were monitored for skeletal-related events, bone disease progression, and death. The relative risks (RRs) and 95% confidence intervals (CIs) for these outcomes were estimated for patients with high versus low levels of each marker using intensity-based multiple event and Cox regression models. All statistical tests were two-sided. RESULTS: In each disease group and overall, high levels of each marker at the beginning of the study were statistically significantly associated with an increased risk of negative outcomes. Use of recent marker assessments as time-dependent covariates gave even greater prognostic significance. High N-telopeptide levels were a stronger prognostic indicator of negative outcomes than bone-specific alkaline phosphatase levels. In recent assessments, patients with high N-telopeptide levels had an increased relative risk of skeletal-related events (prostate cancer, RR = 3.25, 95% CI = 2.26 to 4.68, P<.001; NSCLC and other solid tumors, RR = 1.79, 95% CI = 1.15 to 2.79, P = .010), disease progression (prostate cancer, RR = 2.02, 95% CI = 1.48 to 2.74, P<.001; NSCLC and other solid tumors, RR = 1.91, 95% CI = 1.16 to 3.15, P = .011), and death (prostate cancer, RR = 4.59, 95% CI = 2.82 to 7.46, P<.001; NSCLC and other solid tumors, RR = 2.67, 95% CI = 1.85 to 3.85, P<.001) compared with patients with low N-telopeptide levels. CONCLUSIONS: Baseline and recent bone marker levels were predictive of negative clinical outcomes in patients with bone metastases secondary to prostate cancer and to NSCLC and other solid tumors. N-telopeptide levels were more consistent prognostic indicators than bone-specific alkaline phosphatase for all tumor types, reflecting the key role of osteolysis in the development of skeletal complications. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/15632381/Bone_turnover_markers_as_predictors_of_skeletal_complications_in_prostate_cancer_lung_cancer_and_other_solid_tumors_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/dji002 DB - PRIME DP - Unbound Medicine ER -