Biological Characteristics and Therapeutic Strategies for Resectable Locally Advanced Esophagogastric Junction Cancer: A Comprehensive Update.

Although the clinical importance of esophagogastric junction (EGJ) cancer is being increasingly recognized, its definition and treatment strategies vary considerably across regions. Recently, new concepts such as the gastroesophageal junction zone have been proposed for classification of EGJ cancer. Moreover, EGJ adenocarcinoma has been shown to possess a heterogeneous molecular profile consisting of both esophageal- and gastric-like phenotypes, indicating the need for EGJ-specific therapeutic strategies. Although international clinical practice guidelines for EGJ cancer have been published, substantial regional differences remain. This review aimed to summarize recent updates on the biological characteristics and management of EGJ cancers. Trials such as TIME and MIRO have demonstrated that minimally invasive surgery (MIS) reduces postoperative complications and improves the early postoperative quality of life. More recently, the MONET trial showed that MIS is not inferior to open esophagectomy in terms of long-term oncological outcomes, and the REVATE trial demonstrated the advantages of robot-assisted surgery over thoracoscopic approaches. Perioperative treatment strategies also differ across regions. Western guidelines recommend 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)-based perioperative chemotherapy, as supported by the FLOT4 and ESOPEC trials, whereas Asian studies, such as RESOLVE and PRODIGY, have demonstrated the efficacy of docetaxel, oxaliplatin, and S-1 or S-1 plus oxaliplatin regimens. The application of immune checkpoint inhibitors is also evolving; although KEYNOTE-585 did not show a survival advantage, the MATTERHORN trial demonstrated that durvalumab plus FLOT significantly improved event-free survival, establishing a new emerging global standard. Future directions include redefining EGJ classification, implementing molecular-guided treatment selection, advancing organ-preserving strategies, and optimizing perioperative immunochemotherapy.