Prognostic and Therapeutic Implications of Tumor Biology, Including Gene Alterations, in Colorectal Liver Metastases

Background For patients with colorectal liver metastases (CLM), the combination of surgical resection with other therapeutic options is essential. This article shows how recent advances in knowledge of tumor biology, including genetic alterations, affect the choice of therapeutic approach for patients with CLM. Methods We reviewed the literature on recent advances in knowledge about CLM tumor biology including genetic profiles, clinical risk score models for CLM, preoperative therapy for CLM, and liver-directed therapy for CLM. Results Studies showed that RAS alteration is a negative prognostic factor in addition to traditional clinical risk factors (e.g., larger diameter and higher number of CLM, spread of the primary tumor to regional lymph nodes). 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. Discussion In patients with CLM, RAS mutation status is important in predicting postoperative survival, selecting the treatment approach, and tailoring postoperative follow-up. In addition, more recent genetic analyses of CLM have identified additional predictors of survival.

Automated summary

In patients with colorectal liver metastases (CLM), recent advancements in understanding tumor biology, including genetic alterations, have influenced the choice of therapeutic approach. Studies have shown that RAS mutation is a negative prognostic factor, and the response to preoperative chemotherapy is crucial for predicting survival outcomes. Genetic analysis using next-generation sequencing has identified additional predictors of survival, such as alterations in TP53, SMAD4, FBXW7, and RAS/BRAF.