Esophageal submucosa: the watershed for esophageal cancer

Objectives: Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival.

Methods: From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression.

Results: As submucosal invasion increased, cancer length (P < .001), width (P < .001), area (P < .001), LVI (P = .007), and grade (P = .05) increased. Invasion of the deep submucosa (P < .001) and LVI (P = .06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle-third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age.

Conclusions: Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs.