Crossroads in the combined-modality management of gastroesophageal junction carcinomas

An epidemiologic shift in esophageal and gastric carcinomas has occurred in recent years in the Western world. Adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is now the predominant esophageal carcinoma, and proximal gastric cancers now account for nearly half of gastric carcinomas. Tumors involving the GEJ appear to be a distinct clinical entity that presents a challenge to oncologists due to issues in staging and classification and uncertainties regarding optimal treatment approach. Beyond surgical resection as the primary treatment modality, the roles of neoadjuvant or adjuvant therapies in GEJ cancers are not clearly defined. This article reviews the major randomized trials of combined-modality treatment in populations with esophageal and gastric cancers that included patients with GEJ carcinomas and discusses how the findings relate to and inform the management of GEJ tumors. In general, preoperative or perioperative chemotherapy appears to improve survival, and the addition of neoadjuvant or adjuvant chemoradiotherapy increases locoregional control and appears to improve survival. Although GEJ tumors account for only 20% to 35% of cancers in the most relevant randomized trials, the available data suggest that trimodality therapy with chemotherapy, radiation, and surgery is a reasonable treatment approach for GEJ tumors. Further clinical trials are needed to define the optimal sequencing and combinations of surgery, radiotherapy, and chemotherapy. These trials should include appropriate definitions and stratification of GEJ tumors in order to facilitate translation of findings to treatment practice.