Impact of Neoadjuvant Chemoradiation on Lymph Node Status in Esophageal Cancer: Post hoc Analysis of a Randomized Controlled Trial

Objective: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy. Background: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC. Methods: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170). Results: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P < 0.001), LN downstaging (pN0, 69.1% vs 47.2%, P = 0.016), and reduction in the median NLNr [16.0 (range, 0-47.0) vs 22.0 (range, 3.0-58.0), P = 0.001] and NLNi [0 (range, 0-25) vs 1.0 (range, 0-25), P = 0.001]. A good histological response (TRG1/2) in the resected esophageal specimen correlated with reduced median NLNi [0 (range, 0-10) vs 1.0 (range, 0-4), P = 0.007]. After adjustment by treatment, NLNi [hazards ratio (HR) (1-3 vs 0) 3.5, 95% confidence interval (CI): 2.3-5.5, and HR (>3 vs 0) 3.5, 95% CI: 2.0-6.2, P < 0.001] correlated with prognosis, whereas NLNr [HR (<15 vs ≥15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR (<23 vs ≥23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018]. Conclusions: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection.