Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies

World J Gastrointest Surg. 2023 Feb 27;15(2):222-233. doi: 10.4240/wjgs.v15.i2.222.


Background: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited.

Aim: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.

Methods: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.

Results: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer.

Conclusion: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

Keywords: Gastrointestinal malignancies; PD-1 blockade; Preoperative; dMMR/MSI-H.