Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma.

Abstract

Signet ring cell (SRC) histology is regarded as a poor prognostic indicator for esophageal cancer. The objectives of this study were to understand the clinical presentation and stage-specific survival outcomes of patients with SRC and nonsignet adenocarcinoma (AC). From 2004 to 2016, 140,324 patients were diagnosed with esophageal and gastroesophageal junction cancers in the National Cancer Database. Demographics, tumor variables, and treatment were studied. Overall survival was shown by the Kaplan-Meier method, and random survival forest identified important predictors. SRC patients (N = 3825) comprised roughly 3% of esophageal cancers per year. SRC patients were less likely to present at early stage disease (cStage I: 10.2% vs 17.8% for AC; P < .001) and more likely to have pathologic upstaging (28% vs 16%, P < .001) and less pathologic downstaging after neoadjuvant therapy (36% vs 48%, P < .001). More SRC patients had positive margins after resection (15% vs 6.0%, P < .001). In a stage-matched comparison median survival for SRC patients was worse than for AC patients (cStage I: 60 vs 113 months; cStage II: 31 vs 40 months; cStage III: 22 vs 30 months). Clinical tumor and nodal stage, chemotherapy sequence, and age were important predictors of survival. SRC patients had worse survival than their AC counterparts. Worse biology and higher rates of incomplete resection in SRC should steer patients away from undergoing limited resection, such as endoscopic submucosal dissection, even when identified at very early stages. In future esophageal cancer staging iterations, separating SRC from AC appears to be indicated because of their different clinical behavior and response to therapy.