Abstract
BackgroundMutation 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.MethodsCEA 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.ResultsFor 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).ConclusionsHigh 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.
Highlights
Colorectal cancer (CRC) is the third most common cancer and 40–50% of patients with CRC will develop distant metastases.1 Systemic therapy is the main treatment option for metastatic CRC, and better treatment during the past decades has resulted in improved survival
Mutations in RAS and BRAF (V600E) in the tumour cells are associated with impaired prognosis,2–6 and mutation status is routinely used in the clinical management of patients with metastatic colorectal cancer (mCRC)
The present results indicate that carcinoembryonic antigen (CEA) is an independent prognostic biomarker in mCRC in adjusted models including RAS/BRAF mutation status
Summary
Colorectal cancer (CRC) is the third most common cancer and 40–50% of patients with CRC will develop distant metastases. Systemic therapy is the main treatment option for metastatic CRC (mCRC), and better treatment during the past decades has resulted in improved survival. Mutations in RAS (exons 2–4) and BRAF (V600E) in the tumour cells are associated with impaired prognosis, and mutation status is routinely used in the clinical management of patients with mCRC. 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. 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. 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
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