RAS mutation: site of disease and recurrence pattern in colorectal cancer

Somatic mutation status in metastatic colorectal cancer (CRC), and namely mutational activation of the Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene, is becoming more and more relevant in clinical practice. In this review, we describe the current data about the importance of associations between the mutational activation status of the KRAS oncogene and clinical outcomes, prognosis and metastatic patterns of CRC. The presence of a KRAS mutation is detected in approximately 30-50% of CRC and represents a powerful predictor of oncologic outcomes. It is associated with low response to systemic chemotherapy and for insensitivity to the anti-EGFR antibodies in the preoperative setting. It is more frequently associated with right colon cancer. In non-metastatic patients, KRAS mutation leads to more aggressive disease with shorter recurrence free survival (RFS) and more lung recurrences. After resection of CRC liver metastases (LiM), KRAS mutation is directly associated with increased risk of recurrence, worse overall survival (OS), and a distinct metastatic pattern with more invasive intrahepatic recurrence and increased recurrence outside of the liver, particularly in the lung, the peritoneum, and even in uncommon metastatic sites such as the brain and bones. As metastasectomy with curative intent is increasingly considered, a comprehensive approach of tumor biology is required to face the specific challenge of patients with metastatic CRCs. Thus, as it represents one of the strongest predictors of oncologic outcomes, integrating the KRAS mutational status at all the different stages of patient care appears crucial in order to adapt both medical and surgical strategies.