Surgery, radiotherapy, and chemotherapy in carcinoma of the esophagus

Esophageal carcinoma remains a highly lethal disease that has shown a recent profound increase in prevalence and an equally dramatic epidemiologic shift. There is a well recognized causal association between gastroesophageal reflux disease and adenocarcinoma of the esophagus, and the molecular events underlying this progression from mucosal injury, to metaplasia, to dysplasia, to carcinoma are now becoming clear. Current diagnostic modalities and preoperative staging systems all have significant limitations. Fortunately, chemoprevention strategies and the identification of clinically useful molecular biomarkers that may be used to stage disease and select appropriate therapy are on the horizon. The extent of surgical resection for esophageal carcinoma remains an area of great controversy. Disease that is confined to the mucosa is being diagnosed more commonly, and endoscopic ablative techniques have been proposed. To date, however, preoperative discrimination of tumor depth and presence of regional nodal metastases remains inadequate in these very early lesions, and caution is urged before adopting therapies that may compromise cure. For disease penetrating the mucosa, the extent of surgical therapy must be tailored by the objectives of treatment (cure vs palliation) and preoperative stage. Surgical resection is the current standard of care, with combined-modality therapy reserved for prohibitive surgical candidates. No clear survival benefit has been documented for neoadjuvant radiotherapy or chemotherapy alone. The results of preoperative combined-modality therapy, including three prospective, randomized trials, are encouraging but to date have not shown a definite benefit.