Personalized medicine in metastatic colorectal cancer: Hype or reality?

The liver is the most common site of metastasis for patients with colorectal cancer, and resection is associated with significantly improved survival for selected patients. Advancements in perioperative care, operative technique, and multidisciplinary management have led to improved outcomes for patients with colorectal liver metastases (CLM). The objective of this talk is to discuss recent advances in perioperative management, patient selection and prognostication, and surgical technique that make up the state-of-the-art management for patients with CLM. Studies showed that RAS alteration is a negative prognostic factor in addition to traditional clinical risk factors (e.g., tumor diameter and tumor number). Although the response to preoperative chemotherapy is an important predictor of survival, poor response is not a contraindication to surgical resection. The combination of surgical therapy and percutaneous ablation can be considered in marginally resectable cases; however, a wider ablation margin is required for RAS-mutant CLM. More recently, genetic analysis using next-generation sequencing showed the negative prognostic impact of alterations in TP53, SMAD4, FBXW7, and RAS/BRAF in patients with CLM. In RAS-mutant CLM, intensive follow-up is required in patients who remain recurrence free 2 years after surgery. Novel approaches to prognostication such as circulating tumor DNA (ctDNA) may evolve as a revolutionary instrument for patient selection and treatment sequence. RAS alteration, number and diameter of CLM, and primary lymph node metastases are well known risk factors for recurrence after resection of CLM. However, for patients free from recurrence at 2 years after CLM resection, only RAS alteration is associated with recurrence. Thus, it is reasonable to stratify surveillance intensity by RAS alteration status after 2 years. Our group recently proposed a surveillance algorithm in which surveillance is tailored according to the changes over time in recurrence risk and risk factors.