Clinical outcomes in curatively resected dMMR/MSI-H colon cancer: A retrospective analysis of a multicentric cohort.

Abstract

3633 Background: Deficient mismatch repair (dMMR) colon cancer accounts for approximately 15% of localised cases and, despite favourable long-term survival after curative resection, disease recurrence remains a key concern. Recent trials reported a 3-year disease-free survival (DFS) of about 80% after primary surgery with or without adjuvant chemotherapy. In the NICHE-2 trial (Chalabi et. al, NEJM 2024), with the addition of nivolumab plus ipilimumab in the neoadjuvant setting, no relapses were observed at three years. The same immunotherapy doublet provides a 3-year overall survival rate of 81% in the metastatic setting (Lonardi et. al , ESMO 2025). Methods: We conducted a retrospective multicentric cohort study including patients with non-metastatic dMMR/MSI-H colon cancer who underwent resection at 3 Belgian hospitals between January 1, 2013 and December 31, 2020. Patients with synchronous metastases, microsatellite stable (MSS) tumours or insufficient follow-up data (<3 years of imaging surveillance) were excluded. Clinical characteristics, adjuvant therapy, relapse incidence and survival outcomes were analysed. Results: A total of 219 patients with curatively resected dMMR/MSI-H colon cancer were included. Median age was 74 years (range 24–95). Of the total cohort, stage I accounted for 18.3%, stage II for 58.9% and stage III for 22.8%. Adjuvant chemotherapy was administered in 67 patients (30.7%). Relapse occurred in 11 patients (5.0%), comprising 4 patients with stage II disease and 7 patients with stage III disease. The 3-year DFS was 96.2% (95% CI: 96.1-96.3%). Of those relapsing, 7 received subsequent immunotherapy, yet 3 of those ultimately succumbed to the disease. The 5-year disease-specific mortality was 1.99% (95% CI: 1.96-2.03%), while the 5-year overall mortality was 10.3% (95% CI: 9.89-10.81%). Based on the NICHE-2 benchmark, preventing all 3-year recurrences and disease-specific deaths in this cohort would require treating approximately 26 patients with neoadjuvant nivolumab plus ipilimumab to avert one recurrence, and about 73 patients to prevent one cancer-specific death. Conclusions: In this multicentric Belgian cohort of curatively resected dMMR/MSI-H colon cancer, recurrence rates were lower than those observed in the FoXTROT trial (Morton et. al, JCO 2023), even when accounting for the slightly higher proportion of stage I disease in our cohort. Most patients, however, died from other non-related causes, reflecting the well-known enrichment of MSI-H colon cancer in elderly women. A trade-off between neoadjuvant nivolumab plus ipilimumab versus primary surgery and salvage treatment with the same regimen should be discussed based on the high numbers needed to treat to avoid one recurrence and the non-trivial immunotherapy related toxicity (de La Fouchardiere et. al , Annals of Oncology 2024).