Impact of mismatch repair status and adjuvant chemotherapy on long-term oncologic outcomes in high-risk stage II colon cancer: a retrospective study

Abstract Background This study aimed to evaluate the prognostic impact of mismatch repair (MMR) status and adjuvant chemotherapy in patients with high-risk stage II colon cancer, as previous findings have been controversial. Methods This retrospective study included patients with high-risk stage II colon cancer who underwent surgical resection between January 2008 and December 2017. MMR status was determined immunohistochemically by assessing MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2) expression. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. An interaction between MMR status and adjuvant chemotherapy was assessed. Results Mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) tumors were observed in 29/185 (15.7%) and 156/185 (84.3%) patients, respectively. The median follow-up was 120 months. dMMR tumors were more frequently right-sided ( P < 0.001) and associated with high-grade histology ( P < 0.001). No significant differences in OS or DFS were observed between dMMR and pMMR tumors ( P = 0.622 and P = 0.951, respectively). Among dMMR patients, no statistically significant association between adjuvant chemotherapy and OS or DFS was observed. In pMMR patients, adjuvant chemotherapy was associated with better OS in unadjusted analysis but not after multivariate adjustment. No significant interaction between MMR status and adjuvant chemotherapy was observed for OS ( P for interaction = 0.708) or DFS ( P for interaction = 0.923). In multivariate analyses, older age (OS: hazard ratio [HR], 1.080, 95% confidence interval [CI]: 1.053–1.109; P < 0.001; DFS: HR, 1.063, 95% CI: 1.038–1.089; P < 0.001), inadequate lymph node sampling (OS: HR, 2.263, 95% CI: 1.146–4.467; P = 0.019; DFS: HR, 2.082, 95% CI: 1.060–4.091; P = 0.033), and ≥grade IIIa complications (OS: HR, 2.981, 95% CI: 1.406–6.322; P = 0.004; DFS: HR, 2.666, 95% CI: 1.275–5.578; P = 0.009) were independently associated with worse OS and DFS. Conclusions No statistically significant differences in long-term OS or DFS were detected between dMMR and pMMR high-risk stage II colon cancer. The association between adjuvant chemotherapy and survival did not significantly differ by MMR status. Older age, inadequate lymph node sampling, and major postoperative complications were associated with poor survival outcomes. These findings should be interpreted cautiously given the small dMMR subgroup and retrospective design.