Limitations of molecular biomarkers in patients with resectable colorectal liver metastases

Surgeons are exploring the use of molecular biomarkers in patients with colorectal liver metastases (CLM) to improve preoperative prognostication and selection. This is important because surrogate markers of tumor biology remain insufficient to predict clinical outcomes. In the current literature, there is agreement for the association between RAS and BRAF mutations and poor long-term outcome after hepatectomy. While this knowledge is gradually being implemented in the clinical work-up of patients, their limitations and implications have yet to be fully understood. Recent data indicate that combinations of coexisting mutations may refine the molecular scoring into footprints of good and bad. This already complex information must be interpreted in light of recent understanding of clonal heterogeneity and genetic diversity of colorectal cancer and CLM. In the clinical settings, it is important to approach new insight into molecular biomarkers with caution. However, it is likely that in the future, genomic analysis will determine which patient is amenable to surgery or not, the timing of surgery versus other modalities, as well as how to approach the metastases technically. Here we review current knowledge about molecular biomarkers in the treatment of CLM and the limitations to consider at the translation to clinical practice.