Mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) in rectal cancer patients treated with standard neoadjuvant therapy: a systematic review and meta-analysis

Abstract

Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H) is an established biomarker in early-stage colon cancer and metastatic colorectal cancer. However, its prognostic significance in early-stage rectal cancer patients treated with neoadjuvant therapy remains uncertain. We aimed to fill this gap by conducting a systematic review and meta-analysis of the available evidence. PubMed, Embase and Scopus were systematically searched from inception to 11/03/2025 for studies comparing the outcome of dMMR/MSI-H and MMR proficient/microsatellite stable (pMMR/MSS) rectal cancer patients treated with neoadjuvant therapy. Studies of immune checkpoint inhibitors were excluded. Data on pathologic complete response (pCR), pathologic tumor regression grade (pTRG), disease-free survival (DFS) and overall survival (OS) were extracted. Pooled odds ratios (ORs) and hazard ratios (HRs) with their 95 % confidence interval (95 % CI) were calculated using a random effects model. After screening 705 records, 26 retrospective studies were included, the majority of patients being treated with long-course chemoradiotherapy. There was a significant association between dMMR/MSI-H status and pCR (OR 1.50 [95 % CI: 1.04–2.14]; p = 0.03), while no association was found for pTRG (OR 0.77 [95 % CI: 0.44–1.34]; p = 0.326), DFS (HR 1.00 [95 % CI: 0.50–2.01]; p = 0.998) and OS (HR 1.42 [95 % CI: 1.00–2.01]; p = 0.051). Despite the limited data, subgroup analyses did not appear to reveal any significant difference by type of neoadjuvant treatment. In conclusion, patients with dMMR/MSI-H rectal cancer treated with standard neoadjuvant therapy are more likely to achieve a pCR than those with pMMR/MSS tumors.