Endoscopic Ultrasonography-Derived Maximum Tumor Thickness and Tumor Shrinkage Rate as Independent Prognostic Factors in Locally Advanced Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy

Abstract

Neoadjuvant chemoradiotherapy (NCRT) is increasingly used in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Endoscopic ultrasonography (EUS)-derived maximum tumor thickness (MTT) before and after standard NCRT for LA-ESCC indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT. We retrospectively enrolled patients with LA-ESCC who underwent EUS examination pre- and post-NCRT from 2017 to 2021. MTT was measured using EUS. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cut-off value defining the EUS response was determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier (KM) curves were used to calculate overall survival (OS) and progression-free survival (PFS). Data from another center were also used for external validation testing. The median follow-up period was 30.6 months.230 patients with LA-ESCC who underwent EUS pre- or post-NCRT were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the re-examined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. In the whole group the 1-year and 3-year OS rates were 93.9% and 67.9%, and PFS rates were 77.7% and 54.1%, respectively. Thinner post-MTT (≤8.8 mm) and EUS-responders (tumor shrinkage rate≥52%) were independently associated with better OS. The result of EUS-respond was an independent prognostic factor could be confirmed in the external validation group. Among LA-ESCC patients with initial ultrasonic T2-3 staging and T4 staging, no statistically differences were observed between the responder and non-responder groups (P = 0.082; P = 0.190). EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT. Initial tumor infiltration beyond esophageal adventitial layer on ultrasound effect could not, however, predict the long-term prognosis.