Impact of lymphatic ablation approaches on immunotherapy efficacy in advanced/metastatic esophageal squamous cell carcinoma: A multi-institutional retrospective cohort study.

Immune checkpoint inhibitor (ICI)-based therapy is standard care for advanced or recurrent esophageal squamous cell carcinoma after radical treatment, yet the effect of prior lymphatic interventions on ICI efficacy remains unclear. Because tumor-draining lymph nodes serve as key hubs of anti-tumor immunity, this study evaluated how prior lymphadenectomy or nodal irradiation influences subsequent ICI outcomes. We retrospectively analyzed 507 patients, including 302 with recurrent esophageal squamous cell carcinoma after surgery or radiotherapy and 205 with treatment-naïve advanced disease, all treated with ICI-based regimens. In the postoperative recurrence group, an optimal lymph node yield range emerged. Patients with 16-22 dissected lymph nodes (DLNs) achieved significantly longer progression-free survival (PFS; 12.20 months) than those with ≤16 DLNs (7.17 months) or >22 DLNs (6.37 months). DLN group remained an independent prognostic factor for PFS in multivariate analysis. Among patients with post-radiotherapy recurrence, prior involved-field irradiation correlated with significantly longer PFS than elective nodal irradiation (8.30 vs. 5.10 months). These findings suggest an association between prior lymphatic intervention and PFS in patients receiving immunotherapy. A moderate extent of lymphadenectomy and the use of IFI were associated with improved PFS. These results underscore the importance of carefully balancing locoregional disease management with preservation of lymphatic immune architecture in the immunotherapy era.