Efficacy and Safety of Immune Checkpoint Inhibitor-Based Neoadjuvant Therapy Combinations in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis
In brief
Short-course radiotherapy plus chemoimmunotherapy achieves 34% complete response in MSS rectal cancer
In a meta-analysis of 29 trials (1865 patients), combining immune checkpoint inhibitors with short-course radiotherapy and chemotherapy produced a pathological complete response in about one-third of pMMR/MSS locally advanced rectal cancers, roughly twice the rate of non-ICI regimens, while severe toxicity remained under 20%. Larger trials are needed to confirm these findings.
- Journal
- Clinical colorectal cancer (Q1)
- Published
- 19 August 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Xiya Jia, Guoyou Zhang, Yiming Lv, Fei Wang, Chuanxi Lai, Yiyi Chen, et al.
- PMID
- 42767848
- DOI
- 10.1016/j.clcc.2026.08.002
Why clinicians should know about it
- Picked for Gastroenterology (paper of the day, 23 September 2026): Neoadjuvant ICI combos, promising efficacy in rectal cancer
Abstract
Neoadjuvant immunotherapy has shown remarkable efficacy in mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer (LARC), whereas mismatch repair-proficient/microsatellite stable (pMMR/MSS) tumors have historically been resistant because of an immunosuppressive tumor microenvironment. Recently, immune checkpoint inhibitor (ICI)-based combinations with chemoradiotherapy or total neoadjuvant therapy have shown encouraging activity in pMMR/MSS LARC, though their efficacy, safety, and optimal design remain unclear. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and major conference proceedings were searched for trials evaluating neoadjuvant ICI-based therapy in pMMR/MSS LARC. The primary endpoint was pathological complete response (pCR), with major pathological response (MPR), clinical complete response (cCR), sphincter-preserving surgery (SPS), and adverse events as secondary endpoints. Data were synthesized using single-arm, pairwise, and network meta-analytical approaches to evaluate the efficacy, safety and relative treatment rankings. Twenty-nine studies (1865 patients) were included. Pooled pCR, MPR, cCR, and SPS rates were 34%, 62%, 32%, and 82%, respectively, while grade ≥ 3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) occurred in 19% and 4% of patients. Subgroup analyses indicated higher pCR with short-course radiotherapy (SCRT) and higher MPR with concurrent radioimmunotherapy. Compared with non-ICI controls, ICI-based regimens significantly improved pCR (OR 2.12) and MPR (OR 2.03) without increasing severe toxicity. The network meta-analysis ranked SCRT plus chemoimmunotherapy highest for achieving pCR (P-score = .95). ICI-based neoadjuvant therapy, particularly SCRT plus chemoimmunotherapy, shows promising efficacy without a significant increase in severe toxicity in pMMR/MSS LARC, warranting validation in large-scale trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.