Neoadjuvant therapy vs. surgery alone for esophageal squamous cell carcinoma undergoing thoracoscopic esophagectomy:An overlap weighting analysis.

BACKGROUND

The survival benefit of neoadjuvant therapy (NAT) in patients with esophageal squamous cell carcinoma (ESCC) undergoing thoracoscopic esophagectomy (TE) remains controversial. This study aims to evaluate the long-term survival impact of NAT followed by surgery versus surgery alone (S-alone) in this population.

METHODS

This ambispective cohort study retrospectively collected baseline data and prospectively followed patients until July 2022. All enrolled patients had ESCC and underwent TE between January 2015 and December 2016. Patients were divided into the NAT group (n = 269) and the S-alone group (n = 569). The primary outcome was 5-year overall survival (OS), with 5-year disease-free survival (DFS) as a secondary outcome. After balancing baseline characteristics with overlap weighting (OW), survival outcomes were analyzed with weighted Cox regression. Sensitivity analyses based on propensity score matching (PSM) and matching weights (MW) were conducted to test the results.

RESULTS

This study included 838 patients with ESCC who underwent TE. The median OS for the entire cohort was 5.32 years, and the median DFS was 5.13 years. After OW, all covariates were balanced between the groups. Kaplan-Meier analysis with the log-rank test showed no statistically significant differences in 5-year OS or DFS between the two groups (P > 0.05). The weighted hazard ratio (HR) for 5-year OS was 0.98 (95% confidence intervals, CI: 0.72,1.35) and for 5-year DFS was 1.00 (95% CI: 0.75,1.33). Subgroup analysis showed that NAT was associated with a survival benefit in patients with clinically node-positive ESCC (P < 0.05). Sensitivity analyses were aligned with the primary analysis.

CONCLUSIONS

NAT followed by surgery did not improve OS or DFS compared to S-alone in patients with ESCC undergoing TE. However, subgroup analysis suggested a potential survival benefit for patients with more advanced disease. These findings support a stage-guided, individualized approach to NAT in ESCC rather than its uniform application.