Lymph node involvement in esophageal adenocarcinoma: If you see one, have you seen them all?

See related article on page 1121. B arely 50 years ago, the very existence of a primary adenocarcinoma of the esophagus was debated, and this rare tumor was a novelty in comparison with squamous cell esophageal cancer. Yet in one of the most dramatic epidemiologic transformations ever recorded, adenocarcinoma has become the predominant form of esophageal cancer, and the incidence of this cancer continues to increase in all age groups in the United States. Although both squamous cell carcinoma and adenocarcinoma of the esophagus are deadly diseases, the existence of a precursor lesion (Barrett) for esophageal adenocarcinoma has allowed significant advances in our understanding of the pathogenesis and natural history of this cancer. Increasingly, early adenocarcinoma is detected either within a surveillance program for Barrett or fortuitously during an endoscopy to evaluate symptoms of reflux. Many of these patients have superficial tumors and are cured with surgical resection alone, disproving previously held concepts that esophageal cancer is systemic and essentially incurable in all patients at the time of diagnosis. The increasing incidence of esophageal adenocarcinoma and the fact that many of these patients are otherwise healthy permits an accurate assessment of the natural history of the disease and the effect of specific therapies on the course of the illness. Experience at several centers has demonstrated that one of the most important predictors of both survival and the risk of systemic disease in patients with esophageal adenocarcinoma is the presence and extent of involved lymph nodes. Although the current American Joint Committee on Cancer Staging system for esophageal carcinoma only classifies disease as N0 (no involved nodes) or N1 (1 or more involved nodes), distinct survival curves can be produced on the basis of the number, as well as the ratio, of involved to total resected lymph nodes. The depth of tumor invasion is also important, but most of the importance relates to the direct correlation between the depth of invasion and the prevalence of nodal metastases. In this issue of the Journal, Lerut and colleagues examine the influence of lymph node involvement, and in particular extracapsular tumor extension, on the survival of patients undergoing primary surgical resection for adenocarcinoma of the esophagus. All patients in this retrospective study had T3 tumors and had undergone an R0 resection without neoadjuvant therapy. Similar to data from other centers, 83% of these patients with transmural tumors had one or more involved lymph glands, as determined by histologic examination. Importantly, that means that 17% of patients with locally advanced tumors did not have any lymph node metastases, and the 57% 5-year survival in these patients was significantly better than that of patients who had lymph node metastases. We also found that 16% of patients with transmural tumors had no involved lymph nodes, and the 5-year survival for this group of patients after en bloc resection alone was 85% in our experience. An interesting aside is that the percentage of patients with locally advanced tumors without nodal involvement is similar to the percentage of patients who are found to have a complete pathologic response after neoadjuvant chemoradiotherapy. Furthermore, the survival in this group is quite similar to the survival reported for the subgroup of patients with a complete pathologic response in several randomized trials comparing neoadjuvant chemoradiotherapy plus surgical intervention with surgical intervention alone. Recently, Jiao and associates have shown that From the Department of Cardiothoracic Surgery, Keck School of Medicine, the University of Southern California, Los Angeles, Calif.