Impact of liver metastasis on the efficacy of immune checkpoint inhibitors for advanced colorectal cancer

BACKGROUND Liver metastasis is common in advanced colorectal cancer (CRC) and may influence the response to immune checkpoint inhibitors (ICIs). However, the prognostic impact of liver metastasis on ICI efficacy remains uncertain. AIM To evaluate the association between liver metastasis and survival outcomes in patients with metastatic CRC (mCRC) treated with ICIs in a meta-analysis. METHODS We systematically searched PubMed, EMBASE, and Web of Science up to May 14, 2025, for studies comparing survival outcomes in patients with mCRC with vs without liver metastasis receiving ICIs. Hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) were extracted and pooled using random-effects models. Subgroup and sensitivity analyses were conducted to explore heterogeneity and result stability. RESULTS Sixteen studies comprising 1203 patients were included. Liver metastasis was associated with significantly worse PFS [HR = 1.94, 95% confidence interval (95%CI): 1.56-2.41, P < 0.001; I 2 = 38%] and OS (HR = 2.10, 95%CI: 1.66-2.65, P < 0.001; I 2 = 23%) among patients with mCRC treated with ICIs. Subgroup analyses showed consistent results across study design, microsatellite status, age, follow-up duration, and statistical adjustment (P for subgroup difference all > 0.05). Sensitivity analyses performed by excluding one study at a time showed consistent results, which further confirmed the robustness of the findings. CONCLUSION Liver metastasis is associated with worse survival outcomes in patients with mCRC receiving ICIs. These results suggest that liver metastasis may serve as a negative prognostic factor in the context of immunotherapy for mCRC.