Neoadjuvant Combination Immunotherapy for Colorectal Cancer: Clinical and Molecular Predictors of Pathological Complete Response and Safety Assessment

Purpose To identify the clinical and molecular factors that effectively predict pathological complete response (pCR) and assess the safety of patients receiving neoadjuvant combination immunotherapy. Materials and Methods This retrospective study evaluated 81 patients with colorectal cancer (CRC) at a Chinese tertiary center between 2015 and 2023. The cohort included 24 patients with deficient mismatch repair (dMMR) tumors and 57 patients with proficient mismatch repair (pMMR) tumors. Patients were treated with a neoadjuvant combination of immunotherapy and surgery. Results We enrolled 81 patients who were divided into pCR (39.3%) and non-pCR (79.7%) groups. The factors significantly associated with a higher pCR rate after neoadjuvant combination immunotherapy were younger age, low carcinoembryonic antigen (CEA) level, high tumor mutational burden (TMB) level before treatment, clinical stage III, absence of lymph node metastasis before treatment, MSI-H level, dMMR, and pole status mutation. Preoperative combined chemotherapy and targeted therapy also influenced the pCR rate. Neoadjuvant combination immunotherapy showed an overall adverse event (AE) rate of 29.6%, with none of grades 3–4. Surgery-related adverse reactions (srAEs) were also absent for grades 3–4, and 14 of the 81 patients experienced grade 1–2 AEs. Conclusion Neoadjuvant combination immunotherapy resulted in a favorable pCR rate in patients with CRC. Young age, pretreatment CEA level, TMB level, clinical stage, lymph node metastasis, MSI, MMR, and pole status can be used as indicators of the efficacy of neoadjuvant combination immunotherapy. The incidence of AEs from neoadjuvant combination immunotherapy and surgery was low, indicating that this regimen is safe and feasible.