The Evolving Paradigm of Esophageal and Esophagogastric Junction Adenocarcinoma: Current Insights, Emerging Therapies, and Future Directions

Author(s): Regan Laird, Anshu Aggarwal, and Devendra K. Agrawal

Adenocarcinoma of the esophagus and esophagogastric junction is a highly aggressive malignancy with a significant mortality risk and poor overall prognosis. The annual incidence of esophageal adenocarcinoma has risen substantially in recent decades and is now recognized as the most common form of esophageal cancer. Early detection of esophageal adenocarcinoma remains challenging due to the frequency of asymptomatic disease progression and ongoing limitations of current screening guidelines. Barrett’s esophagus is the established precursor lesion for esophageal adenocarcinoma. Despite the high mortality rate of esophageal adenocarcinoma, neoplastic progression of Barrett’s esophagus is poorly understood. While the presence of dysplasia can help identify the relatively small subset of patients with Barrett’s esophagus at a higher risk of progression, it is far from a perfect predictor. More research is needed to understand the underlying mechanisms precipitating malignant transformation. Optimal management of esophageal adenocarcinoma requires a coordinated, multidisciplinary approach to tailor risk-stratified screening algorithms and ensure timely intervention. Advancements in treatment protocols, molecularly targeted therapies, and palliative care have improved perioperative outcomes and quality of life. Even still, long-term survival is poor, and recurrence is frequent. Ongoing translational research is essential for reducing disease burden, improving treatment durability, and extending progression-free survival for patients with esophageal adenocarcinoma. This comprehensive review will detail the established guidelines, recent updates, and deficits surrounding the history, diagnosis, staging, treatment, and prognosis of esophageal adenocarcinoma.