| Summary: | Background: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of <i>KRAS</i> on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request <i>KRAS</i> testing in each situation. Methods: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type <i>KRAS</i>, mutated <i>KRAS</i> and impractical <i>KRAS</i> according to their oncological variables. The impractical (not tested) <i>KRAS</i> group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan–Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. Results: Of the 108 patients identified, 35 cases had <i>KRAS</i> wild-type, 50 cases had a <i>KRAS</i> mutation and the remaining 23 were classified as impractical <i>KRAS</i>. Significantly longer medians for OS, HRFS and DFS were found in the impractical <i>KRAS</i> group. In the multivariable analyses, the <i>KRAS</i> mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35–100.62; <i>p</i> = 0.010 for <i>KRAS</i>), for DFS (HR: 10.06; 95% CI: 2.40–42.17; <i>p</i> = 0.002 for <i>KRAS</i>) and for OS (HR: 4.55%; 95% CI: 1.37–15.10; <i>p</i> = 0.013). Conclusion: Our study considers the possibility of unnecessary <i>KRAS</i> testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., <i>KRAS</i> in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.
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