Current status and advances in the treatment of colorectal cancer with liver metastases

Table 1 Summary of treatment strategies for colorectal liver metastases

Treatment category	Key findings
Surgical resection	Surgical resection is the only potentially curative approach. Patients achieving complete resection show a median survival of 35 months and 5-year survival rates of 35%-58%. Prognostic factors: Primary lymph node status, number/size of liver metastases, interval between primary and metastatic detection, preoperative CEA levels[12-16]. 80%-90% of patients are initially deemed unresectable[9,17,18]
Systemic therapy	MDT improves survival (MDT group: Median OS 42.0 months vs non-MDT 37.0 months)[16,24,25]. Neoadjuvant therapy aims to downsize tumors, assess biology, and select responders, but may induce hepatic injury (e.g., SOS or steatohepatitis)[3,24,27,28]. Chemotherapy ORR: 40%-55%, targeted therapies (anti-EGFR/anti-VEGF) combined with chemotherapy improve conversion rates (31% vs 20%)[11,17,29-31]
Concurrent vs staged surgery	Concurrent surgery: Advantages: Single anesthesia, shorter hospitalization, lower costs. Risks: Higher complication rates in high tumor burden patients (34.0% vs 14.8%)[38-43]. Staged surgery: Advantages: Optimizes patient status, assesses neoadjuvant response. Risks: Prolonged treatment timeline, tumor progression risk[44-47]. No significant difference in long-term survival (HR = 1.13)[48-50]
Local-regional therapy	Stereotactic body radiotherapy: Median PFS 12 months, no severe hepatic toxicity[52-54]. Thermal ablation: Effective for small lesions or combined with surgery[55,56]. Interventional therapies (TACE, Y90, HAIC): Improve conversion rates (11%-38%) and survival (e.g., Y90 median OS = 29.4 months)[57-65]
Immunotherapy/targeted therapy	Immunotherapy: PD-1/CTLA-4 inhibitors effective in dMMR/MSI-H patients (pembrolizumab median PFS 16.5 months vs chemotherapy 8.2 months)[66-68]. Targeted therapy: Anti-EGFR (cetuximab) and anti-VEGF (bevacizumab) remain foundational, emerging combinations (e.g., TGF-β inhibitors) under investigation[74-79]
Prognostic factors	Key predictors: Primary lymph node positivity, > 1 liver metastasis, largest tumor > 5 cm, interval < 12 months, CEA > 200 ng/mL[80-83]. Emerging biomarkers: CtDNA + (increased recurrence risk), KRAS mutations (median OS 26.6 vs 42.5 months), NLR > 4.6 (reduced OS)[84-87]
Future directions	Optimize biomarkers (e.g., TMB, PD-L1) for personalized therapy. Explore combination strategies (e.g., immunotherapy + TME modulators) to overcome resistance. Define optimal timing/sequencing of local-regional and systemic therapies[90,91]

CEA: Carcinoembryonic antigen; MDT: Multidisciplinary management; OS: Overall survival; SOS: Sinusoidal obstruction syndrome; ORR: Objective response rate; EGFR: Epidermal growth factor receptor; VEGF: Vascular endothelial growth factor; HR: Hazard ratio; PFS: Progression-free survival; TACE: Transarterial chemoembolization; Y90: Yttrium-90; HAIC: Hepatic arterial infusion chemotherapy; PD-1: Programmed cell death 1; CTLA-4: Cytotoxic T lymphocyte-associated antigen-4; dMMR: Defective mismatch repair; MSI-H: High microsatellite instability; TGF-β: Transforming growth factor-β; CtDNA: Circulating DNA; NLR: Neutrophil-lymphocyte ratio; TMB: Tumor mutational burden; PD-L1: Programmed cell death ligand 1; TME: Tumor microenvironment.