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Background <p>Immunotherapy shows promise in enhancing pathological responses in locally advanced esophageal squamous cell carcinoma (LA-ESCC), but its long-term survival benefits remain uncertain. This study aims to evaluate the impact of adding immunotherapy to neoadjuvant chemotherapy (nCT) on survival in ESCC patients.</p> Methods <p>From five medical centers, 273 ESCC patients were studied, receiving either neoadjuvant chemoimmunotherapy (nICT) or nCT. Recurrence-free survival (RFS) was the primary endpoint, with locoregional recurrence-free survival (L-RFS) and distant metastasis-free survival (D-MFS) as secondary endpoints. To address confounding biases, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized. An 18-month landmark analysis and Kaplan–Meier curves assessed survival differences.</p> Results <p>The pathological response was significantly improved in the nICT group compared to the nCT group. Cox analysis confirmed nICT as an independent factor associated with better prognosis (HR = 3.05, 95% CI 1.81–5.14, <i>p</i> &lt; 0.001). Before matching, the nICT group showed superior RFS (<i>p</i> &lt; 0.001), L-RFS (<i>p</i> = 0.002), and D-MFS (<i>p</i> &lt; 0.001). After PSM, nICT showed its advantage in RFS (<i>p</i> &lt; 0.001) and D-MFS (<i>p</i> = 0.003), with a trend toward improved L-RFS (<i>p</i> = 0.075). Similarly, after IPTW, nICT maintained its survival benefit in RFS (<i>p</i> = 0.001), D-MFS (<i>p</i> = 0.015), with an observed trend toward enhanced L-RFS (<i>p</i> = 0.085). Stratified analyses revealed greater survival benefits of nICT in patients with ypStage III/IV (<i>p</i> &lt; 0.001). The 18-month landmark analysis demonstrated that nICT significantly enhanced RFS (<i>p</i> &lt; 0.001), L-RFS (<i>p</i> = 0.048), and D-MFS (<i>p</i> &lt; 0.001) with the first 18 months after surgery.</p> Conclusion <p>nICT substantially improves prognostic outcomes in LA-ESCC patients, especially in terms of D-MFS and the period of the first 18-month post-surgery, suggesting nICT could be a more effective treatment strategy. Besides, more prospective investigations are required to substantiate these findings.</p> Graphical abstract <p></p>

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The enhanced pathological response from additional immunotherapy improved recurrence-free survival for esophageal squamous cell carcinoma: a multi-center cohort study

  • 期刊论文

  • 发表日期：

    2025年8月25日

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  • Shuhan Xie,
  • Hui Xu,
  • Jinxin Xu,
  • Zilu Tang,
  • Shijie Huang,
  • Jinbiao Xie,
  • Rongyu Xu,
  • Sunkui Ke,
  • Hai Zhang,
  • Mingqiang Kang

摘要

Background

Immunotherapy shows promise in enhancing pathological responses in locally advanced esophageal squamous cell carcinoma (LA-ESCC), but its long-term survival benefits remain uncertain. This study aims to evaluate the impact of adding immunotherapy to neoadjuvant chemotherapy (nCT) on survival in ESCC patients.

Methods

From five medical centers, 273 ESCC patients were studied, receiving either neoadjuvant chemoimmunotherapy (nICT) or nCT. Recurrence-free survival (RFS) was the primary endpoint, with locoregional recurrence-free survival (L-RFS) and distant metastasis-free survival (D-MFS) as secondary endpoints. To address confounding biases, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized. An 18-month landmark analysis and Kaplan–Meier curves assessed survival differences.

Results

The pathological response was significantly improved in the nICT group compared to the nCT group. Cox analysis confirmed nICT as an independent factor associated with better prognosis (HR = 3.05, 95% CI 1.81–5.14, p < 0.001). Before matching, the nICT group showed superior RFS (p < 0.001), L-RFS (p = 0.002), and D-MFS (p < 0.001). After PSM, nICT showed its advantage in RFS (p < 0.001) and D-MFS (p = 0.003), with a trend toward improved L-RFS (p = 0.075). Similarly, after IPTW, nICT maintained its survival benefit in RFS (p = 0.001), D-MFS (p = 0.015), with an observed trend toward enhanced L-RFS (p = 0.085). Stratified analyses revealed greater survival benefits of nICT in patients with ypStage III/IV (p < 0.001). The 18-month landmark analysis demonstrated that nICT significantly enhanced RFS (p < 0.001), L-RFS (p = 0.048), and D-MFS (p < 0.001) with the first 18 months after surgery.

Conclusion

nICT substantially improves prognostic outcomes in LA-ESCC patients, especially in terms of D-MFS and the period of the first 18-month post-surgery, suggesting nICT could be a more effective treatment strategy. Besides, more prospective investigations are required to substantiate these findings.

Graphical abstract