Pathological Complete Response and Residual Disease Patterns After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Clinical and Laboratory Associations

Background: Pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma may differ between the primary tumor and regional lymph nodes. We evaluated pretreatment factors associated with pathological complete response (pCR) and the anatomical distribution of residual disease after esophagectomy. Methods: This retrospective single-center cohort included 100 patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. pCR was defined as ypT0N0. Associations with pCR were evaluated using logistic regression. Results: Among 99 response-evaluable patients, 59 achieved pCR (59.6%; 95% CI, 49.7–68.7%). Of 40 patients with non-pCR, residual disease involved only the primary tumor in 26 (65%), both primary and nodal compartments in 10 (25%), and only regional lymph nodes despite complete primary tumor regression in 4 (10%). Overall, 14 patients with non-pCR (35%) had residual nodal disease. In an exploratory adjusted analysis that could not account for baseline cT and cN categories, lower pretreatment lactate dehydrogenase (OR per 10 U/L increase, 0.93; 95% CI, 0.86–0.99; p = 0.026) and female sex (OR, 2.72; 95% CI, 1.02–7.24; p = 0.045) were associated with pCR. Conclusions: Response was heterogeneous across primary tumor and nodal compartments. Primary tumor regression did not invariably indicate nodal clearance, supporting compartment-specific response assessment. The lactate dehydrogenase and sex associations may reflect residual confounding by baseline disease extent and require external validation.