Does adding immunotherapy to neoadjuvant chemotherapy increase postoperative morbidity in gastroesophageal junction adenocarcinoma? A propensity score-matched study.

BACKGROUND

Landmark trials have established the surgical feasibility of neoadjuvant immunotherapy plus chemotherapy (NICT) in gastric and esophageal cancers, yet data specific to the narrow anatomical confines of the gastroesophageal junction (GEJ) remain limited. This study aimed to compare postoperative morbidity between patients receiving NICT and those receiving neoadjuvant chemotherapy (NCT) alone.

METHODS

This single-center, retrospective cohort study included consecutive patients with locally advanced GEJ adenocarcinoma (Siewert II/III) undergoing curative resection after NICT (n=140) or neoadjuvant chemotherapy alone (NCT, n=260). Propensity score matching (1:1) balanced baseline characteristics, including dMMR/MSI-H status and surgical approach, yielding 120 matched pairs. The primary outcome was major complications (Clavien-Dindo ≥III). Secondary outcomes included specific surgical complications, immune-related adverse events (irAEs), and interval to surgery.

RESULTS

After matching, NICT was associated with improved major pathological regression (58.3% vs. 45.8%; p=0.028). The primary endpoint was not significantly different between NICT and NCT cohorts (25.8% vs. 22.5%; p=0.538). Critically, no differences were observed in specific technical complications, including anastomotic leak (11.7% vs. 10.0%), conduit failure (3.3% vs. 2.5%), or pulmonary events. irAEs occurred in 13.3% of the NICT cohort without delaying surgical intervention. Multivariable and sensitivity analyses confirmed NICT was not an independent predictor of morbidity.

CONCLUSION

This analysis provides anatomically focused evidence that the addition of immunotherapy to neoadjuvant chemotherapy for GEJ adenocarcinoma is not associated with a statistically significant increase in risk of major postoperative morbidity, anastomotic failure, or operative complexity. While larger randomized trials remain the gold standard, these findings support the extrapolation of established safety data to the technically demanding GEJ location.