Published online Feb 27, 2023. doi: 10.4240/wjgs.v15.i2.222
Peer-review started: November 29, 2022
First decision: December 27, 2022
Revised: January 8, 2023
Accepted: February 1, 2023
Article in press: February 1, 2023
Published online: February 27, 2023
Neoadjuvant programmed death protein (PD)-1 blockade immunotheapy has been sufficiently applied in a variety of cancers, but was rare in metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies. Since the NICHE Study have showed their inspiring results that neoadjuvant immunotherapy was an efficient and safe method to improve colon cancer patients’ outcome, NCCN guideline then recommend immune checkpoint inhibitors to cT4b gastric or colorectal cancer. However, whether preoperative immunotherapy can expand to other stage gastrointestinal malignancies is still unknown.
We performed this study among 36 initially surgical resected difficult dMMR/MSI-H gastrointestinal malignancies such gastric cancer, duodenal cancer and colorectal cancer patients who received preoperative PD-1 blockade immunotherapy followed by surgery in order to investigate if the indication of preoperative immunotherapy can expand to initially surgical resected difficult dMMR/MSI-H gastrointestinal malignancies and evaluate the safety and efficacy.
To the best of our knowledge, this retrospective study is one of the few to summarize dMMR/MSI-H gastric, duodenal, and colorectal cancers for preoperative immunotherapy. The cohort was a sequential case analysis that only one patient was excluded from the cohort because symptoms disappeared after PD1 therapy and she refused to examination and further treatment.
The limitations of this study included its small sample size, retrospective design, short follow-up time, and different neoadjuvant regimens and cycles. However, our study was a real-world clinical study in patients who required preoperative immunotherapy, and the group was a continuous case cohort, with the exception of one patient who declined to be enrolled because of resolution of symptoms.
Our study demonstrated that preoperative PD-1 blockade immunotherapy with or without chemotherapy could achieve significant effect and acceptable adverse events in dMMR/MSI-H gastrointestinal malignancies.
Our study demonstrated that preoperative PD-1 blockade immunotherapy with or without chemotherapy could achieve significant effect and acceptable adverse events in dMMR/MSI-H gastrointestinal malignancies. Some low rectal cancer or duodenal cancer can achieve clinical complete response and avoid surgery to achieve organ preservation. Large sample clinical trials are needed.
This study compared preoperative immunotherapy for dMMR/MSI-H in different gastrointestinal tumors, and showed that specific treatment strategies could be used for different tumor sites. It was encouraging to find that a high proportion of dMMR/MSI-H duodenal and low rectal cancers did not require surgery after preoperative immunotherapy, and this treatment strategy deserves further investigation.