Are endoscopic therapies appropriate for superficial submucosal esophageal adenocarcinoma? An analysis of esophagectomy specimens.

BACKGROUND: Endoscopic resection and ablation have advanced the treatment of intramucosal esophageal adenocarcinoma and have been promoted as definitive therapy for selected superficial submucosal tumors. Controversy exists regarding the prevalence of nodal metastases at various depths of mucosal and submucosal invasion. Our aim was to clarify this prevalence and identify predictors of nodal spread.

STUDY DESIGN: An expert gastrointestinal pathologist retrospectively reviewed 54 T1 adenocarcinomas from 258 esophagectomy specimens (2000 to 2008). Tumors were classified as intramucosal or submucosal, the latter being subclassified as SM1 (upper third), SM2 (middle third), or SM3 (lower third) based on the depth of tumor invasion. The depth of invasion was correlated with the prevalence of positive nodes. Fisher's exact test and univariate and multivariate logistic regression were used to identify variables predicting nodal disease.

RESULTS: Nodal metastases were present in 0% (0 of 25) of intramucosal, 21% (3 of 14) of SM1, 36% (4 of 11) of SM2, and 50% (2 of 4) of SM3 tumors. The differences were significant between intramucosal and submucosal tumors (p < 0.0001), although not between the various subclassifications of submucosal tumors (p = 0.503). Univariate logistic regression identified poor differentiation (p = 0.024), lymphovascular invasion (p = 0.049), and number of harvested lymph nodes (p = 0.037) as significantly correlated with nodal disease. Multivariate logistic regression did not identify any of the tested variables as independent predictors of the prevalence of positive lymph nodes.

CONCLUSIONS: All depths of submucosal invasion of esophageal adenocarcinoma were associated with an unacceptably high prevalence of nodal metastases and a marked increase relative to intramucosal cancer. Accurate predictors of nodal spread, independent of tumor depth, are currently lacking and will be necessary before recommending endoscopic resection with or without concomitant ablation as curative treatment for even superficial submucosal neoplasia.