Ongoing Challenges with Clinical Assessment of Nodal Status in T1 Esophageal Adenocarcinoma

Abstract

Endoscopic mucosal resection (EMR) has emerged as an esophageal-preserving treatment for T1 esophageal adenocarcinoma (EAC); however, only patients with negligible risk of lymph node metastasis (LNM) are eligible. Reliable clinical diagnostic tools for LNM are lacking, as such, several risk assessment scores have been developed. The purpose of this study was to externally validate 2 previously published risk scores (Lee and Weksler) for clinical prediction of LNM in T1 EAC patients. In adherence with the Lee and Weksler scores, esophagectomy patients with pathologic T1 EAC were identified. Sub-analysis was performed in patients with clinical T1 based on EMR. Predictive accuracy of the scores was evaluated by calculating the area under the curve of the receiver operating characteristic curve and calibration plots. The areas under the curves were compared using Venkatraman's test for paired receiver operating characteristic curves. Of 233 patients identified who met study criteria for external validation, 3 T1a and 32 T1b patients had LNM. The receiver operating characteristic curves demonstrated comparable high predictive and discriminatory capabilities with areas under the curves of 0.832 and 0.824 for the Lee and Weksler scores, respectively (p= 0.750). Results were more variable for the EMR cohort. Based on the risk thresholds defined by each score, the false-positive rate compared against the pathologic LNM status were 73% and 56% for Lee and Weksler, with 3% false negatives in the latter. On EMR, the false-positive rates were 70% and 50% for Lee and Weksler, with no false negatives. Both scoring systems demonstrated good discriminatory ability and predictive accuracy for LNM, but the defined thresholds resulted in a high false-positive rate. A better scoring system based on clinical characteristics is needed to better identify patients with local disease.