Prognostic Impact of Bulky Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Multicenter Cohort Study.

BACKGROUND: The prognostic relevance of bulky lymph node metastases in esophageal squamous cell carcinoma (ESCC) after neoadjuvant immunochemotherapy remains uncertain. METHODS: This multicenter retrospective cohort included 1247 patients with thoracic ESCC receiving PD-1 inhibitor-based immunochemotherapy followed by R0 esophagectomy at three Chinese centers during 2020-2025. Bulky nodal disease was defined as a radiologically suspected metastatic lymph node with maximum axial diameter ≥ 20 mm. Pathologic response, nodal downstaging, recurrence, postoperative morbidity, overall survival (OS), and disease-free survival (DFS) were compared. Cox models evaluated prognostic association and incremental value beyond cTNM staging. RESULTS: Bulky nodal disease occurred in 218 patients (17.5%) and was associated with more advanced cT, cN, and cM categories. Pathologic complete response (pCR) (19.3% vs. 21.1%; P = .55) and major pathologic response (48.2% vs. 43.5%; P = .21) rates were comparable. Among cN-positive patients, nodal downstaging was less frequent with bulky disease (40.8% vs. 57.1%; P < .001), with more residual positive lymph nodes (2.5 vs. 1.1; P < .001). Two-year OS was 71.9% versus 77.6% (P = .03), and DFS was 64.3% vs. 73.4% (P = .003). Distant recurrence was more frequent (9.6% vs. 4.7%; P = .004). After additional adjustment for cT, cN, and cM, bulky status was no longer significantly associated with DFS or OS and did not improve model fit. Among patients achieving pCR, survival and recurrence did not differ by bulky status. CONCLUSIONS: Bulky nodal disease marks an imaging-defined high-risk ESCC phenotype characterized by poorer nodal response and observed survival, but its incremental prognostic value beyond cTNM staging appears limited. Pathologic complete response attenuated its adverse prognostic association.