Surgical resection remains the backbone of curative treatment for localized esophageal adenocarcinoma. However, resection alone carries a significant risk of recurrence and is no longer considered an acceptable approach for patients with locally advanced disease. Strategies incorporating perioperative chemotherapy, neoadjuvant chemoradiotherapy, and adjuvant immune checkpoint blockade have significantly improved survival. However, despite these advances, approximately half of all patients with locally advanced disease will experience recurrence and ultimately succumb to their disease. To overcome this innate resistance to cytotoxic therapy, novel strategies are being developed. This review discusses both evidence-based and emerging perioperative approaches and explores potential risk-adapted strategies to individualize perioperative therapy.
Submitted November 11, 2024; final revision received March 19, 2025; accepted for publication March 20, 2025.
Disclosures: Dr. Klute has disclosed receiving grant/research support from and serving as a scientific advisor for Bristol Myers Squibb; and serving as a consultant for Daiichi Sankyo, Pfizer, Genus Oncology, and Oncolys BioPharma. Dr. Shah has disclosed receiving grant/research support from Merck, Bristol Myers Squibb, Oncolys BioPharma; serving as a principal investigator for Merck; serving as a scientific advisor for Merck and Bristol Myers Squibb; and serving as a consultant for Takeda Pharmaceuticals and Astellas Pharmaceuticals.