Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases

SIMPLE SUMMARY: Modern management of colorectal liver metastases (CRLM) requires a thorough knowledge of tumor biology and oncogenes mutations. RAS mutations are of paramount interest for the indication of targeted therapies and is increasingly considered as a negative prognostic factor for patients undergoing surgical resection or ablation for CRLM. Several studies discussed the results of specific technical considerations according to RAS mutational status on the oncological outcomes after surgical resection/ablation for CRLM. We reviewed the available data on the real impact of RAS mutations on the prognosis with special regard to the need of a tailored surgical (ablation) approach according to tumoral biology. ABSTRACT: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.