Neoadjuvant Treatment Strategies for Resectable Proximal Gastric, Gastroesophageal Junction and Distal Esophageal Cancer

SIMPLE SUMMARY: The five-year survival for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer ranges from 30 to 60% globally. Neoadjuvant and/or perioperative therapy has emerged as a treatment tool to improve patient selection for surgery, resectability, and locoregional control of the disease. As a result, treatment strategies have evolved from the first trials in the late 1980s to the pivotal CROSS trial updated in 2015. The review summarizes current clinical trials and treatment recommendations with regard to neoadjuvant and/or perioperative therapy for patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus, GEJ, and proximal stomach. ABSTRACT: 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.