Treatment of resectable colorectal cancer liver metastases: Surgery Surgical resection is still the best treatment for colorectal cancer liver metastases, so all eligible patients should receive surgery at an appropriate time. Some patients with unresectable liver metastases should also undergo surgery at the appropriate time when the lesions become resectable after treatment. Although the criteria for suitability for surgical resection have been evolving, they should be judged mainly from three aspects: (1) the primary colorectal cancer lesion can be or has been radically resected; (2) the metastases can be completely resected (R0) according to liver anatomy and lesion extent, and it is required to preserve normal liver function with residual liver volume of 30% to 50% or more; (3) the patient’s systemic condition allows for the absence of unresectable extrahepatic metastatic lesions. For the treatment of colorectal cancer combined with liver metastases at the time of diagnosis, simultaneous resection of primary foci and liver metastases in stage I or resection in stages in stage II can be used. Both have their advantages and disadvantages: simultaneous resection in stage I has higher surgical risks; stage II resection may result in progression of liver metastases after resection of the primary lesion, significantly prolonging the cumulative hospital stay of patients and relatively higher costs. Clinicians can make a decision by taking into account the patient’s condition and local medical conditions. For liver metastases after radical colorectal cancer surgery, surgical resection is the first choice, usually preceded by neoadjuvant therapy. For postoperative recurrence of resectable liver metastases, secondary, tertiary or even multiple resections of liver metastases can be performed when the patient’s systemic condition and liver condition allow. Similarly, simultaneous or staged resection of extrahepatic metastases such as lung and abdomen should be performed when the patient’s systemic condition permits, if they can be completely resected. Neoadjuvant and adjuvant treatment For liver metastases combined with colorectal cancer at the time of diagnosis, neoadjuvant treatment can be considered when there is no bleeding, obstruction or perforation at the primary site. If systemic chemotherapy is used, regimens include 5-fluorouracil + calcium folinic acid + oxaliplatin (FOLFOX), 5-fluorouracil + calcium folinic acid + irinotecan (FOLFIRI) or capecitabine + oxaliplatin (CapeOX). Molecularly targeted therapies can also be combined, but their efficacy remains controversial: bevacizumab may increase bleeding during liver surgery and postoperative wound problems, and it is recommended that the timing of surgery should be chosen 6-8 weeks after the last bevacizumab treatment; cetuximab is only suitable for patients with wild-type KRAS gene. Combined hepatic artery infusion chemotherapy may also be considered. To reduce the adverse effects of chemotherapy on liver surgery, neoadjuvant chemotherapy is in principle limited to 6 cycles, and it is generally recommended to complete chemotherapy and perform surgery within 2 to 3 months. For patients with liver metastasis after radical colorectal cancer surgery, without chemotherapy after resection of the primary site or who have completed chemotherapy 12 months before the discovery of liver metastasis, neoadjuvant therapy can be administered for 2 to 3 months (in the same way as above). For patients who have received chemotherapy within 12 months prior to the discovery of liver metastases, neoadjuvant chemotherapy has a limited role, and direct resection of liver metastases followed by postoperative adjuvant therapy may be considered, as well as preoperative combination with hepatic artery infusion chemotherapy. Patients with completely resected liver metastases, especially those who have not received preoperative chemotherapy and adjuvant chemotherapy, should receive postoperative adjuvant chemotherapy with a recommended duration of 6 months, and may also be considered in combination with hepatic artery infusion chemotherapy and molecular targeted therapy. Given that bevacizumab may be detrimental to surgical wound healing, it is recommended that it be started after 5 weeks postoperatively. In addition, cetuximab is only suitable for patients with wild-type KRAS gene. For patients who have completed preoperative chemotherapy, the duration of postoperative adjuvant chemotherapy can be appropriately shortened. Treatment of unresectable colorectal cancer liver metastases Comprehensive treatment principles For patients with unresectable colorectal cancer liver metastases, comprehensive treatment should be adopted, including systemic and interventional chemotherapy, molecular targeted therapy and local treatment for liver lesions (such as radiofrequency ablation, anhydrous alcohol injection, radiotherapy, etc.). Radiofrequency ablation is currently only used as a treatment option after ineffective chemotherapy or as a postoperative recurrence treatment for liver metastases. If systemic chemotherapy, hepatic artery infusion chemotherapy or radiofrequency ablation are ineffective, radiation therapy is considered but not recommended for routine application. Other methods include intra-tumor injection of anhydrous alcohol, cryotherapy and Chinese medicine treatment, but their efficacy is not superior to each of the above treatments, and they are only used as part of the comprehensive treatment, and may lose their therapeutic significance when used alone. Some unresectable liver metastases at the initial diagnosis can be converted to be suitable for surgical resection after systematic comprehensive treatment, and the 5-year survival rate after surgery is similar to that of the initial liver metastases resection. Comprehensive treatment can also significantly prolong the median survival and improve the quality of life of patients with inoperable colorectal cancer liver metastases. Combined liver metastases at diagnosis For patients with inoperable liver metastases at diagnosis of colorectal cancer, if there is bleeding, obstruction or perforation of the primary lesion, the primary lesion should be removed first, followed by systemic chemotherapy (or additional hepatic artery infusion chemotherapy), which can be combined with molecular targeted therapy. Liver ultrasound, enhanced computed tomography (CT) or (and) magnetic resonance imaging (MRI) evaluation is performed after every 2 to 3 cycles of treatment. If the liver metastases turn out to be resectable, they are treated surgically. If the liver metastases remained unresectable, comprehensive treatment was continued. If there is no bleeding, obstruction or perforation of the primary lesion, the primary lesion may be resected and further treated (as above) or treated with systemic chemotherapy (or additional hepatic artery infusion chemotherapy) for 2 to 3 months in combination with molecular targeted therapy. If the metastases become resectable, surgical treatment (simultaneous resection in stage I or staged resection) will be performed. If the liver metastases remain unresectable, the primary lesion will be resected as appropriate, and the comprehensive treatment of the liver metastases will continue after surgery. For patients with potentially resectable liver metastases, it is recommended to increase the intensity of chemotherapy appropriately, and the 5-fluorouracil + calcium folinate + irinotecan + oxaliplatin (FOLFOXIRI) regimen can be considered, and can be combined with molecular targeted therapy. Despite the promising efficacy of targeted drugs, the combination of multiple targeted drugs is not recommended at present. Liver metastases after colorectal cancer resection Patients with unresectable liver metastases after colorectal cancer surgery can be treated with systemic chemotherapy. The current first-line chemotherapy regimens for liver metastases from colorectal cancer include FOLFOX and FOLFIRI, which can be used as a second line for each other. Patients who have received adjuvant chemotherapy with FOLFOX within 12 months before the occurrence of liver metastasis should be treated with FOLFIRI regimen, and molecular targeted therapy or combined with hepatic artery infusion chemotherapy can be added. For patients who have received prior 5-fluorouracil + calcium folinic acid or capecitabine monotherapy, those who have not received prior chemotherapy, or those who have received FOLFOX adjuvant chemotherapy more than 12 months ago, they may be treated with FOLFOX, FOLFIRI, or a previously effective chemotherapy regimen with the addition of molecularly targeted therapy, or combined with hepatic artery infusion chemotherapy. Liver ultrasound, CT or (and) MRI evaluation is performed after every 2-3 cycles of treatment. Patients whose liver metastases turn out to be resectable should be treated immediately with surgery and followed by adjuvant chemotherapy. If the liver metastases remain unresectable, the combination therapy will be continued.