Cancer research and treatment · 2026
The Role of Adjuvant Chemotherapy in High-Risk Stage II Colon Cancer with Microsatellite Instability-High or DNA Mismatch Repair Deficiencies: A Multicenter Pooled Analysis (KCSG-CO24-03).
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Hur Joon Young, Kim Hana, Lee Soon Il, Park Se Jun, Yun Jina, Kang Seok Yun, Kim Cheolsik, Beom Seung-Hoon, Kim Hyeyeong, Jeon So-Yeon, Jo Jaemin, Noh Yongho, Kim Jong Gwang, Bang Hyun Jin
Аннотация
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.
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.