Current Standards and Controversies in Multidisciplinary Management of Locoregional Gastroesophageal Junction Tumors

There has been controversy in the management of gastroesophageal (GE) junction cancers with pre-operative chemoradiation and peri-operative chemotherapy as accepted practices. We aim to assess and compare the defining trials establishing current standards of care and discuss future directions seeking to further improve patient-centered outcomes in GE junction cancers.

Over the last two decades, several large Phase III randomized trials have been conducted including GE junction cancers, showing superiority of 1) pre-operative chemoradiation over surgery (CROSS) and 2) peri-operative chemotherapy with FLOT over CROSS without radiotherapy (FLOT 4). While NEO-Aegis suggested equipoise between the CROSS vs. peri-operative chemotherapy, the recently presented ESOPEC trial demonstrated superiority of peri-operative FLOT versus CROSS in esophagus and GE junction adenocarcinomas.

Based on the ESOPEC trial, peri-operative chemotherapy with FLOT appears to be a preferred regimen for patients with resectable GE junction adenocarcinomas in patients able to receive FLOT. There is evidence in support of other practices, such as induction chemotherapy, pre-operative chemoradiation, definitive chemoradiation for those not fitting ESOPEC criteria. Chemoradiation ± chemotherapy with non-operative intent represents a promising strategy for patients seeking organ preservation, and ongoing studies will better define its feasibility and long-term outcomes.