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).

Abstract

3622 Background: The benefit of adjuvant chemotherapy (CTx) for high-risk stage II MSI-H/dMMR colon cancer remains controversial, with discordant international guidelines. This study evaluated clinical outcomes comparing adjuvant CTx vs. observation in this population. Methods: This multicenter retrospective analysis included 192 patients with high-risk stage II MSI-H/dMMR colon cancer who underwent curative resection (2010-2020). High-risk features included pT4, grade 3-4, lymphovascular invasion, bowel obstruction/perforation, perineural invasion (PNI), inadequate lymph node sampling (<12), or close margins. Primary endpoint was 5-year relapse-free survival (RFS). Secondary endpoints included 5-year overall survival (OS). A propensity score-matched (PSM) analysis was performed. Results: Of 192 patients, 128 (66.6%) received adjuvant CTx (FOLFOX n=66, capecitabine n=40, FL n=17, others n=5) and 64 (33.3%) underwent observation. Median follow-up was 60.5 months. During follow-up, 24 RFS events and 15 OS events occurred. The 5-year RFS was significantly higher with adjuvant CTx versus observation (94.0% vs. 83.7%; P=.001), as was 5-year OS (98.3% vs. 89.0%; P=.001). Multivariate analysis confirmed adjuvant CTx as an independent prognostic factor for both RFS (HR 0.278, 95%CI 0.117-0.660; P=.003) and OS (HR 0.176, 95%CI 0.052-0.594; P=.005). PNI independently predicted worse RFS (HR 4.053; P=.002) and OS (HR 7.490; P=.001). Subgroup analysis demonstrated pronounced benefit in pT4 patients (OS HR 0.094, P=.031; RFS HR 0.230, P=.038) and significant benefit in T3 patients (RFS HR 0.326, P=.031). No survival differences were observed between oxaliplatin-containing vs. non-oxaliplatin regimens (5-year RFS P=.636; OS P=.757). PSM analysis (n=56 pairs) confirmed the survival benefit (matched OS HR 0.344, P=.036). Conclusions: Adjuvant CTx significantly improves RFS and OS in high-risk stage II MSI-H/dMMR colon cancer, particularly in pT4 and PNI patients. The absence of regimen-specific survival differences suggests that treatment administration itself, rather than specific agents, determines outcomes. These findings provide evidence to bridge NCCN and ESMO guideline discrepancies, supporting risk-stratified adjuvant CTx in this population. Multivariate analysis for survival. Relapse free survival Hazard Ratio 95% CI P value Adjuvant chemotherapy No 1 0.117-0.660 0.003 Yes 0.278 Pathologic T stage T3 1 0.955-5.577 0.063 T4 2.308 Perineural invasion No 1 1.627-10.100 0.002 Yes 4.053 Overall survival Hazard Ratio 95% CI P value Adjuvant chemotherapy No 1 0.052-0.594 0.005 Yes 0.176 Age < 60 1 0.607-13.000 0.186 ≥ 60 2.810 Pathologic T stage T3 1 1.223-12.820 0.021 T4 3.959 Perineural invasion No 1 2.184-25.690 0.001 Yes 7.490 Bowel perforation or obstruction No 1 0.933-9.078 0.065 Yes 2.911