Neoadjuvant treatment strategies for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer have evolved over several decades. Treatment recommendations differ based on histologic type—squamous cell carcinoma (SCC) versus adenocarcinoma (AC)—as well as the exact location of the tumor. Recent and older clinical trials in this area were critically reviewed. Neoadjuvant chemoradiation with concurrent taxane- or fluoropyrimidine-based chemotherapy has an established role for both AC and SCC of the distal esophagus and GEJ. The use of perioperative chemotherapy for gastric AC is based on the FLOT4 and MAGIC trials; however, the utility of neoadjuvant chemoradiation in this setting requires further evaluation. Additional clinical trials evaluating chemotherapy, targeted therapy, immunotherapy, and radiation that are currently in process are highlighted, given the need for further disease control.
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