Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H)
Open accessAbstract
Background The microsatellite instability-high (MSI-H) phenotype, present in 15% of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is rare and its impact on outcomes is unknown. We describe survival outcomes and the impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the largest reported cohort of MSI-H metastatic colorectal cancer (CRC).Patients and methods A retrospective review of 55 MSI-H metastatic CRC patients from two institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD Anderson Cancer Center (United States), was conducted. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models.Results Median age was 67 years (20-90), 58% had poor differentiation, and 45% had stage IV disease at presentation. Median overall survival (OS) from metastatic disease was 15.4 months. Thirteen patients underwent R0/R1 metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one patients received first-line systemic chemotherapy for metastatic disease with median OS from the start of chemotherapy 11.5 months. No statistically significant difference in progression-free survival or OS was seen between fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients undergoing metastatectomy (HR 0.11; P = <0.001) and patients who initially presented as stage IV disease had improved OS (HR 0.27; P = 0.003).Conclusions Patients with MSI-H metastatic CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.
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Colorectal cancer exhibiting a dMMR/MSI-H profile tends to be located in the right colon and is accompanied by unfavorable characteristics such as distant lymph node metastases, peritoneal cavity spread, mucus secretion, and poor differentiation.
“CRC exhibiting a dMMR/MSI-H profile tends to be located in the right colon, while a constellation of unfavorable characteristics such as distant lymph node metastases, peritoneal cavity spread, mucus secretion, and poor differentiation accompanies it [41,42].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [41]
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- Authors
- Goldstein, J., Tran, B., Ensor, J., Gibbs, P., Wong, H. L., Wong, S. F., Vilar, E., Tie, J., Broaddus, R., Kopetz, S., Desai, J., & Overman, M. J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Overman, M.J.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 25
- Issue
- 5
- Pages
- 1032-1038
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC4072907
- OpenAlex
- W2140143664
- Cited by
- 288
- References
- 27
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 16 · 2023: 33 · 2022: 30 · 2021: 34 · 2020: 20 · 2019: 26 · 2018: 28 · 2017: 25 · 2016: 33 · 2015: 15 · 2014: 4
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000371)
- National Cancer Institute (P30CA016672)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- metastatic colorectal cancer, microsatellite instability-high, BRAF V600E mutation, metastasectomy, systemic chemotherapy, overall survival, prognostic factors, stage IV disease, fluoropyrimidine, oxaliplatin, irinotecan
- MeSH terms
- Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Female, Humans, Liver Neoplasms, Male, Middle Aged, Prognosis, Retrospective Studies, Colorectal Neoplasms, Multivariate Analysis, Proportional Hazards Models, Treatment Outcome, Mutation, Missense, Proto-Oncogene Proteins B-raf, Kaplan-Meier Estimate, Microsatellite Instability, Young Adult
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