Investigations over the past three decades have resulted in multimodality therapy as the standard of care today for the management of stage II and III esophageal cancer in the United States. During this same time period, there has been a shift in the dominant histology and primary location from squamous cell cancer of the midesophagus to adenocarcinoma of the distal esophagus and gastroesophageal junction. The results of large clinical trials and meta-analyses demonstrate that trimodality therapy (chemoradiation followed by esophagectomy) improves local-regional control and overall survival compared to either single-modality surgery or the sequence of chemotherapy followed by surgery. Concomitant chemoradiation without surgery improves survival and local-regional control compared to radiotherapy alone in patients with squamous cell histology. Thus, surgical and nonsurgical approaches are available for treatment of esophageal cancer in the United States. Current investigations focus on the integration of biologics into current therapies and the identification of prognostic and predictive biomarkers.
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