Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy

BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with non-metastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable non-metastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published during the interim from April to September 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were (1) English-language; (2) adults with primary cancer of the colon; (3) non-metastatic disease; (4) neoadjuvant immunotherapy; (5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASUREs: Safety (Grade 3+ treatment related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7,691 studies identified, 6,370 were screened, and 8 included. Various agents, dosing regimens, and treatment durations were employed, with durations of immunotherapy ranging from 1-16 cycles. Complete R0 resections were consistently achieved in 98%-100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50%-91% had ypT0N0 pathology. The safety profiles were generally favorable, with Grade 1-2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2%-70% of patients. Postoperative complications following neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.