Objective   While immune checkpoint inhibitors combined with chemotherapy have displayed good efficacy in esophageal cancer treatment, to date, no consensus on the application of immunotherapy in the perioperative phase of locally advanced esophageal cancer has been achieved. This study provides a reference and basis for the clinical application of immune checkpoint inhibitors in the neoadjuvant treatment of esophageal cancer by analyzing accumulated patient data. Methods This study collected locally advanced patients with esophageal squamous cell carcinoma who were diagnosed by pathology at The Fourth Hospital of Hebei Medical University from March 2020 to August 2021. After evaluation, it was recommended to undergo neoadjuvant therapy combined with immune checkpoint inhibitors, and then undergo standardized esophageal cancer radical surgery. A total of 152 patients were included. The observed endpoints were pathologic complete response (pCR) rate, major pathologic response (MPR) rate, R0 resection rate, postoperative complications, tumor regression grade , and disease-free survival (DFS) rate. The optimal number of cycles of neoadjuvant combination therapy was explored.

  Results   A total of 152 patients were enrolled in this study. R0 resection was performed in 143 patients (94.1%), and postoperative pathological evaluation revealed pCR in 45 patients (29.6%). The respective percentages of patients with College of American Pathologists (CAP) grades 0, 1, 2, and 3 were 29.6%, 11.2%, 25.7%, and 33.5%. pCR was 25%, and 16.4% developed neoadjuvant therapy-related adverse events. The postoperative downstaging rate was 62.5%. No deaths occurred within 90 days after surgery, and postoperative complications occurred in 25%, including anastomotic fistula 7.8% and pneumonia 9.2%. The proportion of patients with CAP grade 0～2 after surgery was 92.1% in patients with 2～3 immune-cycles before surgery, while 7.9% in patients with other immune-cycles (P=0.007). The median follow-up time for the whole group was 16.4 (15.0-17.8) months, with a 1-year DFS rate of 96.7% and a 2-year DFS rate of 87.5%.

  Conclusions   PD-1/PD-L1 inhibitors are safe, and neoadjuvant treatment is feasible for patients with locally advanced esophageal squamous cell carcinoma with satisfactory R0 resection and pCR rates. Neoadjuvant chemotherapy, in combination with immune checkpoint inhibitor therapy, achieves stage reduction. Postoperative treatment is limited in most patients, and it is recommended that adjuvant therapy be placed preoperatively when possible. Patients with 2～3 preoperative cycles seem to achieve higher rates of pathological remission.