The role of pathological response in predicting the benefit of adjuvant therapy after neoadjuvant chemoimmunotherapy in patients with esophageal cancer.

Background: Neoadjuvant chemoimmunotherapy has demonstrated significant survival benefits in esophageal squamous cell carcinoma (ESCC), but the value of postoperative adjuvant therapy remains controversial. Tumor regression grade (TRG) serves as a crucial pathological indicator of response to neoadjuvant treatment, yet its role in guiding adjuvant therapy is unclear. This study aimed to investigate the prognostic significance of TRG in postoperative adjuvant therapy.

Methods: This multicenter retrospective cohort study included 169 thoracic ESCC patients who underwent R0 resection after neoadjuvant chemoimmunotherapy between January 2019 and December 2022. Patients were stratified into TRG 0-1 (good response) and TRG 2-3 (poor response) groups. Survival outcomes were analyzed using Kaplan-Meier and Cox regression models.

Results: With a median follow-up of 34 months, adjuvant immunotherapy significantly improved 3-year overall survival (OS) compared to no adjuvant therapy (82.1 % vs. 66.3 %, p = 0.042), though no significant difference in disease-free survival (DFS) was observed. Subgroup analysis revealed that adjuvant therapy notably improved OS in patients with TRG 0-1 (93.2 % vs. 73.3 %, p = 0.015), but not in TRG 2-3. Multivariate analysis confirmed adjuvant immunotherapy as an independent protective factor in TRG 0-1 (HR = 0.22, p = 0.015), while vascular invasion was an adverse factor in TRG 2-3. Additionally, patients with pathological lymph node involvement (yPN+) benefited from adjuvant immunotherapy (HR = 0.41, p = 0.019).

Conclusion: TRG and lymph node status may serve as valuable markers to identify ESCC patients who benefit from adjuvant immunotherapy, facilitating personalized postoperative treatment strategies.