Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer.

ABSTRACT

BACKGROUND: The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples. OBJECTIVE: This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy. METHODS: This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy. RESULTS: 100 patients with mCRC were included in the study. 75% of patients showed concordant results between liquid biopsy and tissue biopsy, while 25% had discordant results. Liquid biopsy demonstrated a sensitivity of 62% and a specificity of 93%. The accuracy of liquid biopsy was 75%, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41%), followed by NRAS (4%) and BRAF (3%). Mutations were not detected in 42% of tissue biopsy samples and 60% of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods. CONCLUSION: Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity.