Multimodality therapy for esophageal cancer

The incidence of esophageal cancer is increasing at an alarming rate in the Western world, primarily because of an increased rate of adenocarcinoma of the distal esophagus. Esophageal cancer is usually discovered late in its course, when symptoms appear. This probably explains the advanced stage, high frequency of lymph node involvement, submucosal tumor spread, and extension into surrounding structures found at the time of diagnosis. Surgery is the treatment of choice for most localized esophageal cancer patients. Despite complete tumor resection and extensive lymphadenectomy, however, systemic and local recurrences are common, and 5-year survival rates range from 15% to 39%. The purported benefit of preoperative administration of chemotherapy, radiotherapy, and combined chemoradiation is that it might downstage the primary tumor, thereby increasing the resectability rate and also eliminating micrometastasis or delay their appearance and prolong survival. Despite a large number of phase II and III studies, the role of such multimodality protocols is still unclear. The results of recent multimodality trials that focus on several different approaches are summarized in this review. In current multimodality protocols for esophageal cancer, local treatment remains either surgery or radiotherapy. Chemotherapy is added to the regimen to decrease the size of the primary tumor, thereby increasing the possibility for complete resection and to eliminate micrometastasis or delay its appearance. Most recent clinical trials have focused on one of three popular combinations of treatment, including (1) systemic therapy followed by surgery, (2) systemic therapy combined with radiotherapy (concomitant or sequential) followed by surgery, or (3) systemic chemotherapy and radiotherapy without surgery. Other combinations of multimodality treatment (such as adjuvant chemotherapy following surgical resection) have been investigated, but they enjoy much less interest than the treatments mentioned above.