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The incidence of esophageal carcinoma in the Western world has increased more than 600% since the 1970s, mainly due to the rising incidence of adenocarcinoma.1 Therapeutic improvements in both early and locally advanced esophageal adenocarcinoma have been in part based on an understanding that gastroesophageal reflux (GER) is a precursor to esophageal cancer leading to a sequence of epithelial changes from metaplasia to progressive dysplasia, ultimately culminating in adenocarcinoma. This understanding coupled with technological advancements in endoscopic and radiographic imaging, have enhanced the surveillance and staging accuracy of esophageal cancer allowing us to both identify patients at an early stage more often, and to select patients with potentially curable disease more reliably.
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Although resection of the esophagus was the mainstay of esophageal cancer treatment in the past, we have learned that even very radical resections combined with other forms of local or regional therapy are not adequate to cure advanced disease in the majority of cases. Distant recurrence continues to be the main cause of death in patients with esophageal cancer.
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THE EVOLUTION AND PRINCIPLES OF MULTIMODALITY THERAPY
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The late 19th and early 20th centuries were marked by Billroth’s2 and Halstead’s3 pioneering developments in the surgical treatment of gastric and breast cancer, respectively. The first successful esophagectomy was performed by Franz Torek in Germany on March 14, 1913, under chloroform and ether anesthesia.4 In situ reconstruction was not performed and enteral continuity was achieved via extracorporeal esophago-gastrostomy utilizing a plastic tube. The patient survived for 12 years, ultimately dying not of cancer but from pneumonia. This landmark event translated into the recognition of the potential for cure of localized esophageal cancers utilizing surgical extirpation. With improvements in perioperative care, surgery became a supplement to radiation as the treatment of choice for localized esophageal cancer in the early 20th century. Over time, more extensive en bloc esophageal resections and lymphadenectomy became favored with the hope that radical resection of disease would result in a cure more frequently. This was similar to Halsted’s approach to radical mastectomy for breast cancer at a time when many patients were dying of poorly controlled local-regional disease. However, we have learned that while this approach may lead to better locoregional control, it fails to achieve cure in a cohort of patients who are ultimately destined to succumb to systemic disease.
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Increased understanding of cancer biology led to the development of nonsurgical treatment strategies for solid organ malignancies combining radiation therapy for local effect and chemotherapy for systemic effect. Intuitively, this strategy addresses both local disease and “sterilizes” potential micrometastases. The demonstrated efficacy of this treatment paradigm has stimulated interest in combining surgery, radiation therapy, and chemotherapy to maximize the treatment effect, and this combination has become the focus of several clinical trials investigating the role and timing of each method.
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Neoadjuvant therapy is based on the ...