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The Role of Adjuvant Chemotherapy in High-Risk Stage II Colon Cancer with Microsatellite Instability-High or DNA
Joon Young Hur1, Hana Kim2, Soon Il Lee3
1Department of Hematology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea. deliverus@amc.seoul.kr.
Purpose:
The benefit of adjuvant chemotherapy (CTx) for high-risk stage II microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colon cancer remains controversial with discordant international guidelines. This study evaluated outcomes comparing adjuvant chemotherapy group versus surgery only group.
Materials And Methods:
This multicenter retrospective analysis included 192 patients with high-risk stage II MSI-H/dMMR colon cancer who underwent curative resection between 2010 and 2020. High-risk features included pT4, grade 3-4, lymphovascular invasion, bowel obstruction/perforation, perineural invasion (PNI), inadequate lymph node sampling (<12), or close margins. The primary endpoint was 5-year relapse-free survival (RFS), excluding second primary malignancies to isolate antitumor efficacy.
Results:
Of 192 patients, 128 (66.7%) received adjuvant CTx and 64 (33.3%) underwent observation (median follow-up 60.5 months). Five-year RFS (94.0% vs. 83.7%; p=0.001) and OS (98.3% vs. 89.0%; p=0.001) were significantly higher with adjuvant CTx. Multivariate analysis confirmed adjuvant CTx as an independent predictor for RFS (HR 0.249, 95% CI 0.109-0.571; p=0.001) and OS (HR 0.155, 95% CI 0.051-0.470; p=0.001). PNI was also identified as a significant independent predictor of RFS (HR, 3.581; 95% CI, 1.529 to 8.387; p=0.003) and OS (HR, 4.968; 95% CI, 1.654 to 14.930; p=0.004). CTx-related toxicities were clinically manageable, and no treatment-related deaths were reported.
Conclusion:
Adjuvant CTx significantly improves RFS and OS in high-risk stage II MSI-H/dMMR colon cancer, particularly in pT4 and PNI patients. These findings provide evidence to bridge NCCN and ESMO guideline discrepancies, supporting risk-stratified adjuvant CTx in this population.
