Anlotinib, a multitarget tyrosine kinase inhibitor, has demonstrated notable activity against esophageal squamous cell carcinoma (ESCC). This study summarizes real-world outcomes comparing chemoradiotherapy (CRT) combined with anlotinib versus CRT alone in individuals who developed lymph node relapse following curative surgery. Records of patients with nodal recurrence treated with CRT with or without anlotinib between January 2017 and December 2019 were retrospectively reviewed. Tumor response, overall survival (OS), progression-free survival (PFS), and treatment-associated toxicity profiles were examined. Propensity score matching (PSM) was applied to equalize baseline factors. Among 291 patients, 76 received CRT plus anlotinib and 215 underwent CRT alone. After PSM, 68 patients from each group were included. The combination group had higher partial response (58.8% vs 41.2%, p = 0.04) and objective response (86.7% vs 61.8%, p = 0.001) rates. OS (3-year OS, 42.7% vs 23.5%, p = 0.008) and PFS (12-month PFS, 47.1% vs 32.4%, p = 0.026) were also superior with anlotinib. Multivariate evaluation confirmed treatment regimen (p = 0.007) as an independent OS predictor. Rates of grade 3–4 adverse reactions were not significantly different (39.5% vs 30.7%, p = 0.162). Adding anlotinib to CRT yielded better survival without increasing high-grade toxicity in postoperative ESCC patients with lymph node recurrence.
