Efficacy and survival analysis of neoadjuvant chemotherapy combined with immunotherapy in locally advanced resectable Siewert type II adenocarcinoma of the esophagogastric junction.

Background: Neoadjuvant chemotherapy combined with immunotherapy (nCI) has achieved significant results in esophageal and gastric cancers, but its efficacy in Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains unclear. This study aims to verify the efficacy and safety of nCI in real-world settings for locally advanced resectable Siewert type II AEG.

Methods: A retrospective analysis of clinical data from 101 patients with locally advanced resectable Siewert type IIAEG who underwent esophagogastric junction resection after chemotherapy combined with Sintilimab in a single-center treatment group from December 2020 to May 2024. The analysis focused on the rates of pathological complete response (pCR), major pathological response (MPR), R0 resection rate, tumor downstaging, recurrence-free survival (RFS), and safety.

Results: A total of 101 patients were included, the median follow-up time was 19.2 months. 74 patients (73.3%) experienced postoperative pathological downstaging, with 78 patients (77.2%) showing postoperative pathological T downstaging and 47 patients (55.3%) showing postoperative pathological N downstaging. Patients with cT3 had better outcomes in pCR, MPR, and postoperative pathological downstaging compared to those with cT4 (pCR 27.9% vs 12.1% p=0.044, MPR 48.8% vs 25.9% p=0.017, postoperative pathological downstaging rate 83.7% vs 65.5% p=0.041). 3-4 cycles of nCI yield a higher pathological complete response (pCR) rate compared to 1-2 cycles (26.7% vs 7.3%,P = 0.015).The one-year RFS rate was 93.1% (95%CI, 88.0%-98.6%), and the OS rate was 93.2% (95%CI, 88.1%~98.6%). The two-year RFS rate was 78.9% (95%CI, 69.1%-90.1%), and the OS rate was 76.0% (95%CI, 65.5%~88.2%). 4 patients (3.96%) experienced grade 3-4 TRAEs, and 7 patients (6.93%) had grade 3-4 surgical complications, with no treatment or surgery-related deaths reported.

Conclusion: Preliminary results indicate that nCI shows promising efficacy in the treatment of resectable locally advanced Siewert type II AEG, with high rates of pCR and MPR, as well as good tolerance and safety. 3-4 cycles of nCI may provide better therapeutic efficacy than 1-2 cycles. These findings require confirmation in prospective head-to-head trials to establish potential long-term clinical benefits.