Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

C de la Piedra, A Alcaraz, J Bellmunt, C Meseguer, A Gómez-Caamano, M J Ribal, F Vázquez, U Anido, P Samper, E Esteban, J L Álvarez-Ossorio, P C Lara, L A San José, J A Contreras, A G del Alba, B González-Gragera, A J Tabernero, C González-Enguita, J M Fernández, A García-Escudero, F Gómez-Veiga, M J Méndez, J Segarra, J A Virizuela, J Carles, A Lassa, V Calderero, M Constela, D Delgado, A Mañas, A Murias, G Reynes, B Rodriguez, G Rubio, E Sánchez, M Unda, E Solsona, J M Martínez-Javaloyas, J Comet-Batlle, C Quicios, M Martín-Fernández, I Mahillo-Fernández, J Morote
British Journal of Cancer 2013 June 25, 108 (12): 2565-72

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA).

METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded.

RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression.

CONCLUSION: In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

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