Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: A BRAF-mutant subset with high CA 19-9 level and poor outcome

Maria Thomsen, Eva Skovlund, Halfdan Sorbye, Nils Bolstad, Kjell Johannes Nustad, Bengt Glimelius, Per Pfeiffer, Elin H. Kure, Julia S. Johansen, Kjell Magne Tveit, Thoralf Christoffersen, Tormod Kyrre Guren

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    9 Scopus citations

    Abstract

    Background: Mutation status of RAS and BRAF, as well as serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are biomarkers used in clinical management of patients with gastrointestinal cancers. This study aimed to examine the prognostic role of these biomarkers in a patient population that started first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC) in the NORDIC-VII study. Methods: CEA and CA 19-9 were measured in serum samples from 545 patients obtained before the start of chemotherapy. Four hundred and ninety-four patients had detectable levels of carbohydrate antigen 19-9 (CA 19-9). RAS (exons 2-4) and BRAF (V600E) mutation status were available from 440 patients. Overall survival (OS) was estimated in patient groups defined by serum CEA or CA 19-9 levels using cut-off values of 5 μg/L and 35 kU/L, respectively, in the total population and in subgroups according to RAS and BRAF mutation status. Results: For both CEA and CA 19-9, elevated serum levels were associated with reduced OS in adjusted analyses which included RAS and BRAF mutation status, baseline World Health Organization performance status, and levels of alkaline phosphatase and C-reactive protein. The negative prognostic information provided by an elevated CA 19-9 level was particularly marked in patients with BRAF mutation (hazard ratio = 4.35, interaction P = 0.003, in an adjusted model for OS). Conclusions: High baseline serum concentrations of CEA and CA 19-9 provide independent information of impaired prognosis in mCRC. In patients with BRAF-mutant tumours, elevated serum CA 19-9 may identify a subgroup with highly aggressive disease and could contribute to improving therapeutic decisions.

    Original languageEnglish (US)
    Pages (from-to)1609-1616
    Number of pages8
    JournalBritish journal of cancer
    Volume118
    Issue number12
    DOIs
    StatePublished - Jun 1 2018

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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    Thomsen, M., Skovlund, E., Sorbye, H., Bolstad, N., Nustad, K. J., Glimelius, B., Pfeiffer, P., Kure, E. H., Johansen, J. S., Tveit, K. M., Christoffersen, T., & Guren, T. K. (2018). Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: A BRAF-mutant subset with high CA 19-9 level and poor outcome. British journal of cancer, 118(12), 1609-1616. https://doi.org/10.1038/s41416-018-0115-9