Zuniga Ingrid, Peros Georgios, Fuchs Ivo, Schreiber Heide, Becker Bjoern, Boehm Steffen and Ortega Sanchez Guacimara*
Colon cancer remains a major cause of cancer-related mortality worldwide, with Locally Advanced Colon Cancer (LACC) accounting for a substantial proportion of newly diagnosed cases. Among these, tumors characterized by Deficient Mismatch Repair (DMMR) or High Microsatellite Instability (MSI-H) represent a distinct molecular subset, comprising approximately 10–15% of cases. While early-stage DMMR colon cancer is associated with a favorable prognosis, its resistance to conventional neoadjuvant chemotherapy has posed challenges in treatment optimization.. The emergence of immune checkpoint inhibitors has revolutionized the management of DMMR metastatic colorectal cancer, prompting investigations into their potential in earlier disease stages. Recent trials, including NICHE and NICHE-2, have demonstrated remarkable efficacy of neoadjuvant immunotherapy in DMMR colon cancer, reporting high Pathological Complete Response (PCR) rates. Despite these promising findings, the broader clinical adoption of neoadjuvant immunotherapy for resectable LACC remains under evaluation, with questions regarding optimal treatment regimens, timing, and patient selection. In this study, we present real-world data from our single-center experience using a combination of nivolumab and ipilimumab as neoadjuvant therapy in patients with DMMR stage III colon cancer. Our findings contribute to the growing body of evidence supporting the efficacy of neoadjuvant immunotherapy in this subset, highlighting its potential to redefine treatment paradigms. Further research is warranted to refine strategies and establish immunotherapy as a standard approach in resectable DMMR colon cancer.