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Yu JJ, Zhu L, Li XP, Wang LP, Meng FG, Sui WX, Feng XJ, Sui YY, Leng P, Yu JM. Efficacy and safety of immune checkpoint inhibitors in the treatment of digestive system cancers: An umbrella review. World J Gastrointest Oncol 2026; 18(12): 124379 [DOI: 10.4251/wjgo.124379]
Jun-Jie Yu, Li Zhu, Xiang-Peng Li, Lu-Ping Wang, Fan-Gang Meng, Wen-Xia Sui, Xiao-Jie Feng, Ying-Ying Sui, Ping Leng, Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Jun-Min Yu, Department of Pain Treatment, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Co-corresponding authors: Ping Leng and Jun-Min Yu.
Author contributions: Yu JJ, Zhu L, Li XP, Wang LP, Meng FG, Sui WX, Feng XJ, Sui YY, Leng P and Yu JM designed the research study; Yu JJ performed the conceptualization, methodology, software, data curation, visualization, and wrote the original draft; Zhu L and Li XP performed the investigation; Wang LP performed the writing of the original draft; Meng FG and Sui WX performed the writing, reviewing, and editing; Feng XJ and Sui YY performed the editing; Leng P and Yu JM performed the conceptualization, supervision, project administration, and funding acquisition, they are co-corresponding authors; all authors read and approved the final manuscript.
AI contribution statement: During the preparation of this work, the authors did not use any generative AI or AI-assisted technologies in the writing or analysis process.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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.
Corresponding author: Jun-Min Yu, MD, Doctor, Department of Pain Treatment, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China. longalley2011@qdu.edu.cn
Received: June 15, 2026 Revised: July 31, 2026 Accepted: October 14, 2026 Published online: December 15, 2026 Processing time: 150 Days and 2.5 Hours
Abstract
BACKGROUND
Digestive system cancers constitute a great burden in clinical practice globally. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway have emerged as important treatment choices. Nevertheless, the certainty of evidence in the systematic reviews and meta-analyses published so far is unclear.
AIM
To investigate the efficacy and safety of PD-1/PD-L1 inhibitors for five digestive system cancers, and to further evaluate the quality of available evidence and the level of certainty.
METHODS
We systematically searched PubMed, Web of Science, EMBASE, and the Cochrane Library for systematic reviews and meta-analyses of ICI treatment for digestive system cancers published up to March 29, 2025. Two independent reviewers screened all records and extracted data. The AMSTAR-1 (a measurement tool to assess systematic reviews) scale tool was used to evaluate methodological quality, and the grading of recommendations assessment, development, and evaluation (GRADE) tool was used to assess certainty of evidence. Hazard ratio and 95% confidence interval for overall survival (OS), progression-free survival (PFS) and recurrence-free survival were extracted, and heterogeneity and publication bias were evaluated.
RESULTS
We reviewed 59 systematic reviews and meta-analyses in all, resulting in a total of 92 survival outcomes. GRADE certainty of the 92 outcomes was: 18 (19.6%) high, 19 (20.7%) moderate, 27 (29.3%) low, 28 (30.4%) very low. For gastric cancer, ICI monotherapy improved OS in selected patients on the basis of biomarkers particularly those with PD-L1 positive or metastatic colorectal cancer. Adding ICIs on first-line chemotherapy, meanwhile, resulted in improved OS and PFS compared with chemotherapy alone. For esophageal cancer, ICI regimens also improved OS and PFS the largest improvement was observed for patients with higher PD-L1 expression. For hepatocellular carcinoma, ICI combinations outperformed sorafenib and other targeted therapies in terms of both OS and PFS. For colorectal cancer however, the evidence was weaker and rated as very low certainty.
CONCLUSION
Our analysis showed that both ICI monotherapy and combination therapy may improve survival in carefully selected patients with gastric, esophageal or hepatocellular cancer. However, more than half of our outcomes were in the low-certainty or very low-certainty categories, and high-certainty evidence is especially lacking in hepatocellular and colorectal cancers.
Core Tip: In this umbrella review, we selected 59 reviews and meta-analyses of programmed cell death protein 1/programmed death ligand 1 (immune checkpoint inhibitors) to determine the effectiveness of these new therapeutics in five digestive system cancers. We applied AMSTAR-1 (a measurement tool to assess systematic reviews) and grading of recommendations assessment, development, and evaluation to map out the hierarchy of evidence. In our review, immune checkpoint inhibitors have activity in gastric and esophageal cancers, but more than half of the outcomes we covered rest on low- or very-low-certainty evidence.
