Optimal management of gastroesophageal junction cancer

Although recent decades have witnessed incremental improvements in the treatment of gastroesophageal junction (GEJ) carcinoma, outcomes remain modest. For locally advanced esophageal cancer, the addition of chemotherapy and/or radiation to surgery is considered the standard of care. Chemotherapy remains the primary treatment for metastatic disease and improves survival over best supportive care. However, the prognosis for patients with GEJ cancers, which are treated along the same paradigms as esophageal and gastric carcinomas, remain poor because of the emergence of chemoresistance and limited targeted therapeutic approaches, which include agents that target the HER2 and vascular endothelial growth factor pathways. Evaluation of immune checkpoint inhibitors in the chemorefractory setting have confirmed the activity of immunotherapy in esophagogastric cancer. Ongoing immunotherapeutic strategies are being evaluated in both the locally advanced and metastatic settings. This review focuses on the treatment of locally advanced and metastatic GEJ carcinomas, which encompass all tumors that have an epicenter within 5 cm proximal or distal to the anatomical Z-line (Siewert classification). Because the vast majority of GEJ tumors are adenocarcinoma, the management of adenocarcinoma is the focus of this review. Evolving approaches and areas of clinical equipoise are discussed.