Safety and feasibility of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced esophageal squamous cell carcinoma: a prospective single-group phase II clinical study.

Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is still the standard treatment mode for esophageal cancer (EC), but the rate of distant metastasis and local recurrence of this triple mode is still high. Distant metastasis is the main recurrence pattern. Therefore, there is an urgent need to explore a new treatment model to improve pathologic complete response (pCR) and patient survival. In recognition of the rise of immunotherapy, this study aimed to investigate the efficacy and safety of nCRT combined with immunotherapy (nRCIT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 22 patients with locally advanced ESCC were enrolled at our institution between 2019 and 2021. The patients underwent nRCIT therapy. The primary endpoint was pCR; secondary endpoints included major pathologic response (MPR), 1- and 2-year overall survival (OS) and disease-free survival (DFS), and adverse events (AEs). Meanwhile, we enrolled 53 patients with ESCC who underwent nCRT at our institution as the control group between 2012 and 2019. A 1:1 propensity score matching (PSM) with a caliper 0.374 was performed to balance potential bias. Results: In present work, 17 patients successfully completed nRCIT and esophagectomy, among whom 16 patients achieved R0 resection. After PSM, age, sex, tumor location, length, alcohol history, body mass index (BMI), clinical T stage, lymph node staging, tumor-node-metastasis (TNM) staging, and cycles of chemotherapy were comparable between groups. After the operation, 7 patients (41.2%) achieved pCR in both primary tumors and lymph nodes. Anastomotic leakage occurred in 3 patients (17.6%) and 1 patient succumbed to pneumonia during the perioperative period. Leukopenia was observed in 20 patients (90.9%) during neoadjuvant therapy, with grade 3 or higher AEs. The 1- and 2-year OS rates are 88.2% and 65.0%, respectively, in the nRCIT group, whereas 34.1% of patients achieved pCR, with 1- and 2-year OS rates of 82.3% and 68.6%, respectively, in the nCRT group. A significant MPR was observed in 10 out of 17 patients (58.8%) in the nRCIT group. Conclusions: nRCIT may appear to be safe and feasible for locally advanced ESCC.