From the Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill-Cornell University Medical College, New York, New York
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to David H. Ilson, MD, Associate Attending Physician and Associate Professor of Medicine, Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill-Cornell University Medical College, 1275 York Avenue, New York, NY 10021; e-mail: ilsond{at}mskcc.org
Overview: Progress has been made in the combined modality treatment of esophageal and gastroesophageal junction cancer. There is an emerging consensus that surgery alone is inadequate therapy for esophageal cancer staged T3 or N1. Primary chemoradiotherapy without surgery is an accepted treatment for esophageal squamous cancer, but also achieves durable disease control in some patients with esophageal adenocarcinoma. Although no consistent benefit is seen for preoperative chemotherapy in esophageal squamous cell or adenocarcinoma, preoperative and postoperative chemotherapy appears to improve survival in gastroesophageal junction adenocarcinoma and gastric cancer compared with surgery alone. Adding radiotherapy to preoperative chemotherapy enhances rates of curative resection and achieves measurable rates of pathologic complete response. Recent trials indicate a survival benefit for preoperative chemoradiotherapy compared with surgery alone in esophageal cancer, particularly in patients achieving a pathologic complete response to combined-modality therapy. Regarding surgery for patients with squamous cancer of the esophagus who respond to combined chemoradiotherapy, there is no clear survival benefit for the addition of surgery after chemoradiotherapy despite improvements in local tumor control with the addition of surgery. After surgery, postoperative combined chemoradiotherapy improves survival for adenocarcinoma of the gastroesophageal junction compared with surgery alone. The toxicity of conventional 5-fluorouracil and cisplatin-based chemotherapy has prompted evaluation of regimens employing taxanes, irinotecan, oxaliplatin, and capecitabine, which are under investigation in combined-modality therapy. Early response assessment with a positron emission tomography scan appears to identify early treatment failures and may direct such patients to early surgery or to alternative chemotherapy. Targeted agents in phases II and III of development include agents targeting the vascular endothelial growth factor pathway and the epidermal growth factor receptor pathway; pilot trials evaluating these agents in combined-modality therapy are ongoing. Tailoring therapy more precisely to individual patients, including early response assessment on positron emission tomography scan, DNA array analysis, and pharmacogenetic profiling for chemotherapy response and resistance, is under active investigation.
