Abstract
BACKGROUND: This study evaluated the prognostic implications of pathological responses of primary tumors (PTs) and lymph nodes (LNs) among locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients received neoadjuvant immunotherapy combined with chemotherapy (nICT). METHODS: This study enrolled patients with LA-ESCC who underwent nICT combined with esophagectomy at Jiangsu Cancer Hospital. Two senior pathologists independently and systematically evaluated the postoperative pathological specimens in a double-blind manner. Tumor regression in PTs was assessed using the Becker criteria, while LNs regression grading was optimized using Harrell's concordance index and the Akaike Information Criterion. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with recurrence patterns as the secondary endpoint. RESULTS: A total of 141 patients with 141 PTs and 2,316 LNs were reviewed. LNs regression classified as LNs complete response (LN-CR); Partial/Poor response (LN-PR); and Truly negative LNs (LNN). The ypT0N0 rate was 21.3%. With median 41-months follow-up (IQR 22-55), the 3-year OS and PFS rates were 61.7% (95% CI 53.3-69.1%) and 48.2% (95% CI 40.2-56.4%), respectively. PTs regression grade was an independent prognostic factor for both OS and PFS (P < 0.05). Multivariable analysis demonstrated that a poorer tumor regression grade (TRG) was significantly associated with increased risks of OS and PFS (P < 0.05). Furthermore, while complete LN-CR correlated with improved PFS compared to LN-PR (P = 0.037), this association did not retain statistical significance in the multivariate analysis. Non-ypT0N0 patients exhibited higher recurrence rates than ypT0N0 (52.3% vs 33.3%, P = 0.047), primarily manifested as mixed progression. CONCLUSIONS: PTs response may constitute a more prominent determinant of both OS and PFS than LNs status, and combining these factors enhances prognostic prediction.