Meta-analysis of neoadjuvant immunotherapy for non-metastatic colorectal cancer

Front Immunol. 2023 Jan 27:14:1044353. doi: 10.3389/fimmu.2023.1044353. eCollection 2023.


Background: Immunotherapy has been approved for the treatment of metastatic colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic colorectal cancer remains unclear. We tried to explore clinical effect of neoadjuvant immunotherapy in the treatment of non-metastatic colorectal cancer.

Methods: We searched the databases (PubMed, Wanfang Embase, Cochrane Library and China National Knowledge Infrastructure databases) to obtain suitable articles up to September 2022. The primary outcomes of pathological complete response (pCRs), major pathological response (MPR), objective response rate (ORR), R0-resection and anus preserving rate were collected and evaluated. Secordary outcomes (pCRs and MPR) of subgroup analysis between deficient mismatch repair/microsatellite instability-high group (dMMR/MSI-H) and proficient mismatch repair/microsatellite stable group (pMMR/MSS) and outcomes for rectal cancer were analyzed for the final results.

Results: We included ten articles and 410 cases of non-metastatic colorectal cancer with neoadjuvant immunotherapy. There were 113 (27.5%) cases with the dMMR/MSI-H status and 167 (40.7%) cases with the pMMR/MSS status. pCRs was found in 167/373 (44.6%) patients (ES: 0.49, 95% CI: 0.36 to 0.62, P<0.01, chi2 = 65.3, P<0.01, I 2 = 86.2%) and MPR was found in 194/304 (63.8%) patients (ES: 0.66, 95% CI: 0.54 to 0.78, P<0.01, chi2 = 42.55, P<0.01, I 2 = 81.2%) with the random-effects model and huge heterogeneity. In the subgroup analysis, pCRs was higher in the dMMR/MSI-H group than the pMMR/MSS group in the fixed-effects model with minimal heterogeneity (OR: 3.55, 95% CI: 1.74 to 7.27, P<0.01, chi2 = 1.86, P=0.6, I 2 = 0%). pCRs was found in 58/172 (33.9%) rectal cancer patients (ES: 0.33, 95% CI: 0.26 to 0.40, P<0.01, chi2 = 3.04, P=0.55, I 2 = 0%) with the fixed-effects model and little heterogeneity.

Conclusion: Neoadjuvant immunotherapy could increase pCRs and MPR rate for non-metastatic colorectal cancer. Neoadjuvant immunotherapy could achieve better pCRs rate in dMMR/MSI-H group than in the pMMR/MSS group. Neoadjuvant immunotherapy could be another treatment option for non-metastatic colorectal cancer.

Systematic review registration:, identifier CRD42022350523.

Keywords: dMMR/MSI-H group; meta-analysis; neoadjuvant immunotherapy; non-metastatic colorectal cancer; pMMR/MSS group.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colonic Neoplasms* / pathology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / therapy
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Microsatellite Instability
  • Neoadjuvant Therapy
  • Rectal Neoplasms*

Grants and funding

This work was supported by the Cancer Hospital of China Medical University. The funding project is Natural Science Foundation of Liaoning Province Fund of China (grant nos.2020-MS-060) and Pilot Cancer Research Fund Project of CSCO (Chinese society of clinical oncology; grant nos.Y-2019AZQN-0035).