Tumor characteristics impact prognosis in deficient mismatch repair/microsatellite instability-high localized colorectal cancer—a systematic review and meta-analysis

BACKGROUND: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) tumors constitute ∼15% of localized colorectal cancers (CRCs). Prognostic biomarkers such as tumor-infiltrating lymphocytes (TILs) and BRAF and KRAS mutations may guide personalized treatment for these patients, and this systematic review and meta-analysis aimed to evaluate their impact on survival outcomes. METHODS: Literature searches were conducted across PubMed, Embase, Cochrane Library, and Web of Science, including studies published between 2004 and 2023. The primary outcomes were overall survival (OS), disease-free survival (DFS), and cancer-specific survival. The risk of bias was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence using the GRADE approach. RESULTS: The literature search yielded 5636 articles. Fifty-four studies were included in the systematic review and 31 studies in the meta-analysis, totaling 4551 patients. High TIL density was significantly associated with improved OS (hazard ratio [HR] = 0.39, 95% CI = 0.17 to 0.89) and DFS (HR = 0.45, 95% CI = 0.29 to 0.71). BRAF and KRAS mutations were seen in 52% and 34% of patients, respectively, and were associated with poorer OS (HR = 1.43, 95% CI = 1.13 to 1.80 and HR = 1.30, 95% CI = 1.09 to 1.54, respectively). Quality of evidence was moderate to high across all exposures and outcomes. CONCLUSION: High infiltration of TILs correlated with improved OS and DFS, whereas BRAF and KRAS mutations were associated with worse OS in patients with localized dMMR/MSI-H CRC. These findings highlight the potential utility of biomarkers for improving prognostic assessment and personalizing management in dMMR CRC.