Therapy optimization in metastatic colorectal cancer guided by discordant KRAS mutation status between primary and metachronous recurrent lesions: a precision oncology case report

Introduction: In stage IV colorectal cancer, molecularly targeted therapies such as anti-EGFR and anti-VEGF antibodies improve patient outcomes. Anti-EGFR therapy is typically effective in RAS wild-type tumors, whereas RAS mutations confer resistance and necessitate alternative strategies. However, discrepancies in RAS status between primary and metastatic lesions may influence treatment response. Presentation of Case: We report a 50-year-old male who underwent resection for rectal adenocarcinoma initially characterized as RAS wild-type. He subsequently developed liver metastases and was treated with FOLFIRI plus panitumumab. While some metastatic lesions regressed, others progressed. Molecular analysis of the liver metastasis revealed a KRAS mutation, in contrast to the primary tumor. The regimen was switched to FOLFIRI plus bevacizumab, which achieved marked regression of all metastatic lesions. Discussion: This case underscores the clinical significance of intertumoral heterogeneity in RAS status. The emergence of a KRAS mutation in the metastatic site explained resistance to anti-EGFR therapy and highlighted the importance of reassessing tumor genetics during disease progression. Tailoring treatment to the molecular profile of the metastatic lesion led to improved clinical outcomes. Conclusion: In colorectal cancer, repeat genetic testing of metastatic lesions should be considered, particularly in cases of treatment resistance. Molecular reassessment may reveal actionable alterations that guide therapy selection and optimize patient management.