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

doi:10.4251/wjgo.v18.i2.115515

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Feb 15, 2026 (publication date) through Feb 3, 2026

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World Journal of Gastrointestinal Oncology

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Meta-Analysis

World J Gastrointest Oncol. Feb 15, 2026; 18(2): 115515
Published online Feb 15, 2026. doi: 10.4251/wjgo.v18.i2.115515

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

Meng-Yue Xiang, Ze-Min Tuo, Xing-Kang Sa, Peng Wang, Ji-Wen Bian, Xin-Ming Zhang

Meng-Yue Xiang, Ze-Min Tuo, Xing-Kang Sa, Department of General Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China

Peng Wang, Department of General Practice, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University, Weifang 261000, Shandong Province, China

Ji-Wen Bian, Department of Oncology, Qingdao Public Health Clinical Center, Qingdao 266000, Shandong Province, China

Xin-Ming Zhang, Department of General Surgery, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital Affiliated of Qingdao University), Qingdao 266000, Shandong Province, China

Author contributions: Xiang MY was responsible for conceptualization, data curation, formal analysis, investigation, methodology, software, resources, validation, writing - original draft, writing - review and editing; Tuo ZM was responsible for data curation, formal analysis, methodology, software, writing - original draft; Sa XK, Wang P and Bian JW was responsible for formal analysis, methodology, software, writing - review and editing; Zhang XM was responsible for conceptualization, investigation, methodology, project administration, resources, supervision, validation, writing - review and editing.

Conflict-of-interest statement: The authors declare that they have no competing interests.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Xin-Ming Zhang, MM, Department of General Surgery, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital Affiliated of Qingdao University), No. 4 Renmin Road, Shibei District, Qingdao 266000, Shandong Province, China. 13963910911@163.com

Received: October 20, 2025
Revised: November 12, 2025
Accepted: December 1, 2025
Published online: February 15, 2026
Processing time: 107 Days and 18.8 Hours

Abstract

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; I² = 38%] and OS (HR = 2.10, 95%CI: 1.66-2.65, P < 0.001; I² = 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.

Keywords: Advanced colorectal cancer; Liver metastasis; Progression; Survival; Immune checkpoint inhibitors

Core Tip: This meta-analysis evaluated the impact of liver metastasis on the efficacy of immune checkpoint inhibitors (ICIs) in advanced colorectal cancer (CRC). By pooling data from 16 studies involving 1203 patients, we found that liver metastasis was significantly associated with poorer progression-free and overall survival among ICI-treated patients. The adverse effect persisted across microsatellite instability subtypes and study designs, highlighting liver metastasis as a robust negative prognostic factor. These findings suggest that liver metastasis may impair systemic antitumor immunity and should be considered when optimizing immunotherapy strategies for metastatic CRC.