Recent updates of therapeutic strategy of esophagogastric junction adenocarcinoma

Abstract

The incidence of esophagogastric junction (EGJ) adenocarcinoma has been increasing in Asian countries. Despite the recent advances in multidisciplinary treatments, EGJ adenocarcinoma remains aggressive with unfavorable outcomes. Regarding surgical strategy, EGJ adenocarcinoma arises between the esophagus and the stomach, and thus tumor cells spread through the lymphatic system both upward to the mediastinum and downward to the abdomen. Nevertheless, an optimal extent of lymphadenectomy remains controversial. Regarding drug therapy, the latest topic in gastric and EGJ adenocarcinoma is trastuzumab deruxtecan, which is an antibody-drug conjugate consisting of an anti-HER2 antibody. In addition, many clinical trials have recently demonstrated the efficacy of immune checkpoint inhibitors. Meanwhile, recent advances in sequencing technology have revealed that gastroesophageal adenocarcinoma could be categorized into four molecular subtypes: epstein-Barr virus-associated, high-level microsatellite instability, genomically stable, and chromosomal instability tumors. Furthermore, these subtypes show distinct clinical phenotypes and molecular alterations. We review the current surgical strategy and drug treatment such as molecular-targeted agents, immune checkpoint inhibitors, and molecular-subtype-based therapeutic strategies in EGJ adenocarcinoma. Clinical and molecular characteristics and response to immune checkpoint inhibitors differ among molecular subtypes. Treatment strategies based on molecular subtypes may be clinically beneficial for patients with EGJ adenocarcinoma.

Keywords

Esophagogastric junction adenocarcinoma / Barrett’s esophagus / microsatellite instability / molecular subtype

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