Comparative effectiveness of neoadjuvant treatment strategies and predictors of pathological complete response in locally advanced esophageal squamous cell carcinoma: a real-world retrospective cohort study

Abstract

To compare pathological complete response (pCR) across different neoadjuvant treatment strategies in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to identify clinicopathological factors associated with pCR. In this single-center retrospective cohort study, 247 consecutive patients with locally advanced ESCC who underwent neoadjuvant therapy followed by radical esophagectomy between January 2024 and June 2025 were included. Patients were categorized into four treatment groups: chemotherapy alone (CT, n = 50), chemoradiotherapy (CRT, n = 38), chemotherapy plus immunotherapy (CT+IO, n = 142), and chemoradiotherapy plus immunotherapy (CRT+IO, n = 17). Pathological complete response was defined as ypT0N0. Clinicopathological characteristics were compared using χ² or Fisher’s exact tests. Factors associated with pCR were evaluated using univariable and multivariable logistic regression analysis. Overall, 63 patients (25.5%) achieved pCR. The pCR rate was lower in the CT group than in the CT+IO group (6.0% vs. 26.8%). After adjustment for potential confounders, chemotherapy alone remained associated with lower odds of pCR than CT+IO (OR = 0.174, 95% CI, 0.046-0.658, P = 0.010). No significant differences were observed between CT+IO and either CRT or CRT+IO. Receipt of more than two neoadjuvant treatment cycles was associated with higher odds of pCR (OR = 2.764, 95% CI, 1.372-5.565, P = 0.004). Compared with cT3 disease, cT2 disease was associated with higher odds of pCR (OR = 3.049, 95% CI, 1.356-6.857, P = 0.007). Neoadjuvant treatment regimen, the number of neoadjuvant treatment cycles, and pretreatment clinical T stage were associated with pathological complete response in locally advanced ESCC. Chemotherapy alone was associated with lower odds of pCR than CT+IO, whereas receipt of more than two treatment cycles was associated with higher odds of pCR. These findings provide real-world evidence regarding factors associated with pathological response.