Bone turnover markers as predictors of mortality risk in prostate cancer patients with bone metastases following treatment with zoledronic acid

Klaus Jung, Kurt Miller, Manfred Wirth, Michael Albrecht, Michael Lein
European Urology 2011, 59 (4): 604-12

BACKGROUND: Clinical data have limited validity for predicting the survival of prostate cancer (PCa) patients with bone metastases. There is a need to improve the predictive evidence both for clinicians and patients.

OBJECTIVE: To evaluate the predictive ability of serum bone markers for mortality risk in PCa patients with bone metastases.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a survival analysis in relation to bone markers in a subgroup of 52 patients treated with zoledronic acid (4 mg every 4 wk for 15 mo) in a prospective, multicentre trial during 2002-2005, about 4 yr after the end of the trial.

MEASUREMENTS: Serum levels of total and bone-specific alkaline phosphatase, amino-terminal procollagen propeptides of type I collagen (PINP), cross-linked N-terminal (NTx) and cross-linked C-terminal telopeptides of type I collagen (ICTP), C-terminal telopeptides of type I collagen, prostate-specific antigen from the last visit of the treatment study, and clinical data were related to the overall survival (OS) status of patients in the follow-up. Univariate and multivariate Cox regression analyses with internal bootstrapping validation and concordance index calculations were performed.

RESULTS AND LIMITATIONS: Out of the 52 patients followed, 34 died within a median follow-up of 13.8 mo, and 18 patients were alive at a median follow-up of 43.8 mo. The patients who died within the follow-up period had significantly higher concentrations of ICTP, NTx, and PINP than the surviving patients. Cox regression models with clinical data and bone markers showed that ICTP and PINP were most predictive for mortality risk in addition to the occurrence of skeletal-related complications and the continuation of treatment with zoledronic acid. Internal validation confirmed the reliability of the results, although the sample size was small.

CONCLUSIONS: PINP and ICTP can be considered suitable predictors for the OS of PCa patients with bone metastases.

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