Association Between Neoadjuvant Immunochemotherapy Efficacy and Pathologic Characteristics in dMMR Gastric/Gastroesophageal Junction Adenocarcinoma

Neoadjuvant immunotherapy (NAIC) is feasible and associated with a high rate of pathologic complete response (pCR) in deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) gastric and gastroesophageal junction cancers (GC/GEJC). However, the association between NAIC efficacy and pathologic characteristics remains unclear. We conducted a retrospective study to evaluate this relationship. Patients with dMMR/MSI-H GC/GEJC who received neoadjuvant immunotherapy were included. The effects of different neoadjuvant regimens were compared, and pathologic characteristics were analyzed between tumor regression grade TRG1 and TRG2 groups. The χ2 test was used to estimate relative risks (RRs) with 95% CIs. In total, 39 patients with dMMR/MSI-H GC/GEJC who received neoadjuvant immunotherapy were included. All patients underwent complete R0 resection; 22 patients (56%) achieved pCR in both the primary tumor and lymph nodes. The chemotherapy plus immunotherapy group and the immunotherapy-only group achieved significantly higher TRG1 rates compared with the chemotherapy group (RR=4.2, 95% CI=1.5-15.0, P=0.0004; and RR=4.4, 95% CI=1.7-15.7, P=0.003, respectively). The intestinal subtype also demonstrated a higher TRG1 rate than the mixed subtype (RR=2.5, 95% CI=1.1-8.7, P=0.0196). Neoadjuvant immunotherapy achieved a high pCR rate in patients with dMMR/MSI-H locally advanced, resectable GC/GEJC relative to chemotherapy. The intestinal subtype may serve as a histologic biomarker of enhanced sensitivity to neoadjuvant immunotherapy in this patient population.