Precision surgery for colorectal liver metastases: Current knowledge and future perspectives

Precision surgery for colorectal liver metastases (CRLM) includes optimal selection of both the patient and surgery. Initial attempts of using clinical risk scores to identify patients for whom technically feasible surgery is oncologically futile failed. Since then, patient selection for single-stage hepatectomy followed three distinct approaches, all of which incorporated biomarkers. The BRAF V600E mutation, the G12V KRAS variant, and the triple mutation of RAS, TP53, and SMAD4 appear to be the most promising, but none can be used in isolation to deny surgery in otherwise resectable cases. Combining biomarkers with clinicopathologic factors that predict poor prognosis may be used to select patients for surgery, but external validation and matched analyses with medically treated counterparts are needed. Patient selection for special surgical procedures (two-stage hepatectomy [TSH], Associating Liver Partition and Portal vein Ligation for staged hepatectomy [ALPPS], and liver transplant [LT]) has been recently refined. Specifically, BRAF mutations and right-sided laterality have been proposed as separate contraindications to LT. A similar association of right-sided laterality, particularly when combined with RAS mutations, with very poor outcomes has been observed for ALPPS and has been suggested as a biologic contraindication. Data are scarce for TSH but RAS mutations may portend very poor survival following TSH completion. The selection of the best single-stage hepatectomy (optimal margin and type of resection) based on biomarkers remains debated, although there is some evidence that RAS may play a significant role. Lastly, although there are currently no criteria to select among the three special techniques based on their efficacy or appropriateness in different settings, RAS mutational status may be used to select patients for TSH, while right-sided tumor in conjunction with a RAS mutation may be a contraindication to LT and ALPPS.