TY - JOUR
T1 - Tumor characteristics impact prognosis in dMMR/MSI-H localized colorectal cancer - a systematic review and meta-analysis
AU - Saqi, Ida Kolukisa
AU - Nielsen, Amalie Thomsen
AU - Madsen, Michael Tvilling
AU - Gögenur, Ismail
AU - Orhan, Adile
AU - Justesen, Tobias Freyberg
N1 - © The Author(s) 2025. Published by Oxford University Press.
PY - 2025/12/4
Y1 - 2025/12/4
N2 - BACKGROUND: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) tumors constitute approximately 15% of localized colorectal cancers (CRC). 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 (CSS). 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. 54 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 (HR = 0.39; 95% CI: 0.17-0.89) and DFS (HR = 0.45; 95% CI: 0.29-0.71). BRAF and KRAS mutations were seen in 52% and 34% of patients, respectively, and were associated with poorer OS (HR = 1.43; 95% CI: 1.13-1.80 and HR = 1.30; 95% CI: 1.09-1.54, 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.
AB - BACKGROUND: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) tumors constitute approximately 15% of localized colorectal cancers (CRC). 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 (CSS). 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. 54 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 (HR = 0.39; 95% CI: 0.17-0.89) and DFS (HR = 0.45; 95% CI: 0.29-0.71). BRAF and KRAS mutations were seen in 52% and 34% of patients, respectively, and were associated with poorer OS (HR = 1.43; 95% CI: 1.13-1.80 and HR = 1.30; 95% CI: 1.09-1.54, 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.
U2 - 10.1093/jncics/pkaf114
DO - 10.1093/jncics/pkaf114
M3 - Review
C2 - 41344844
SN - 2515-5091
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
ER -