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Peer-reviewedCC BY-NC-ND 4.0Cancer Medicine

Discordant Primary Tumor and Nodal Response After Neoadjuvant Chemoimmunotherapy Identifies an Adverse Postoperative Subgroup in Esophageal Squamous Cell Carcinoma

  • Yuxian Qian1,2,3
  • Yuting Ren1,2,3
  • Zhiyun Xu1,2,3,4
  • Rutao Li1,2,5
  • Yipeng Feng1,2,3
  • Hanlin Ding1,2,3
  • Yijian Zhang1,2,3
  • Wenjie Xia1,2
  • Lin Xu1,2
  • Gaochao Dong1,2
  • Feng Jiang1,2
5 affiliations
  1. 1Department of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing P. R. China
  2. 2Jiangsu Key Laboratory of Molecular and Translational Cancer Research Cancer Institute of Jiangsu Province Nanjing P. R. China
  3. 3The Fourth Clinical College of Nanjing Medical University Nanjing P. R. China
  4. 4Department of Thoracic Surgery The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University Huai'an P. R. China
  5. 5Department of Thoracic Surgery The Fourth Affiliated Hospital of Soochow University Soochow P. R. China
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Abstract

Background: Primary‐tumor major pathological response (MPR) and postoperative nodal status are both used to assess response after neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC), but discordant response after neoadjuvant chemoimmunotherapy is poorly characterized. We evaluated a combined primary tumor‐lymph node (PT‐LN) framework for risk stratification.

Methods: This retrospective single‐center cohort included patients treated with two cycles of paclitaxel, cisplatin, and camrelizumab followed by curative‐intent surgery between January 2019 and December 2024. Among 414 screened patients, 367 were included. MPR was defined as 10% or less residual viable tumor cells in the primary tumor. Patients were classified as PT‐MPR/ypN0, PT‐MPR/ypN+, PT‐non‐MPR/ypN0, or PT‐non‐MPR/ypN+. Disease‐free survival (DFS), overall survival (OS), first documented recurrence, and pathological model performance were evaluated.

Results: Sixty‐nine patients (18.8%) had PT‐MPR/ypN+ disease. DFS and OS differed across groups (both overall log‐rank p < 0.001). Compared with PT‐MPR/ypN0, PT‐MPR/ypN+ was associated with worse DFS (baseline‐adjusted hazard ratio [HR], 5.85; 95% confidence interval [CI], 2.82–12.14) and OS (HR, 18.06; 95% CI, 5.53–59.06; both p < 0.001), with similar conclusions after additional pathological adjustment. Regional lymph node recurrence occurred in 44.9% of PT‐MPR/ypN+ patients versus 3.6%, 6.7%, and 16.7% in the other groups (global p < 0.001). The combined PT‐LN framework had 3‐year DFS and OS AUCs of 0.798 and 0.818, with modest gains over LN‐only classification.

Conclusions: Residual nodal disease despite primary‐tumor MPR identifies an adverse phenotype with predominantly regional nodal recurrence. The combined framework is an interpretable stratification approach requiring external validation; surveillance and treatment implications remain hypothesis‐generating.

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Cite

BibTeXRIS
BibTeX
@article{qian2026discordant,
  title = {{Discordant Primary Tumor and Nodal Response After Neoadjuvant Chemoimmunotherapy Identifies an Adverse Postoperative Subgroup in Esophageal Squamous Cell Carcinoma}},
  author = {Yuxian Qian and Yuting Ren and Zhiyun Xu and Rutao Li and Yipeng Feng and Hanlin Ding and Yijian Zhang and Wenjie Xia and Lin Xu and Gaochao Dong and Feng Jiang},
  journal = {Cancer Medicine},
  year = {2026},
  month = nov,
  doi = {10.1002/cam4.72463},
  url = {https://doi.org/10.1002/cam4.72463},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Discordant Primary Tumor and Nodal Response After Neoadjuvant Chemoimmunotherapy Identifies an Adverse Postoperative Subgroup in Esophageal Squamous Cell Carcinoma
AU  - Yuxian Qian
AU  - Yuting Ren
AU  - Zhiyun Xu
AU  - Rutao Li
AU  - Yipeng Feng
AU  - Hanlin Ding
AU  - Yijian Zhang
AU  - Wenjie Xia
AU  - Lin Xu
AU  - Gaochao Dong
AU  - Feng Jiang
PY  - 2026
DA  - 2026/11/05
JO  - Cancer Medicine
DO  - 10.1002/cam4.72463
UR  - https://doi.org/10.1002/cam4.72463
AB  - Background: Primary‐tumor major pathological response (MPR) and postoperative nodal status are both used to assess response after neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC), but discordant response after neoadjuvant chemoimmunotherapy is poorly characterized. We evaluated a combined primary tumor‐lymph node (PT‐LN) framework for risk stratification.  Methods: This retrospective single‐center cohort included patients treated with two cycles of paclitaxel, cisplatin, and camrelizumab followed by curative‐intent surgery between January 2019 and December 2024. Among 414 screened patients, 367 were included. MPR was defined as 10% or less residual viable tumor cells in the primary tumor. Patients were classified as PT‐MPR/ypN0, PT‐MPR/ypN+, PT‐non‐MPR/ypN0, or PT‐non‐MPR/ypN+. Disease‐free survival (DFS), overall survival (OS), first documented recurrence, and pathological model performance were evaluated.  Results: Sixty‐nine patients (18.8%) had PT‐MPR/ypN+ disease. DFS and OS differed across groups (both overall log‐rank p < 0.001). Compared with PT‐MPR/ypN0, PT‐MPR/ypN+ was associated with worse DFS (baseline‐adjusted hazard ratio [HR], 5.85; 95% confidence interval [CI], 2.82–12.14) and OS (HR, 18.06; 95% CI, 5.53–59.06; both p < 0.001), with similar conclusions after additional pathological adjustment. Regional lymph node recurrence occurred in 44.9% of PT‐MPR/ypN+ patients versus 3.6%, 6.7%, and 16.7% in the other groups (global p < 0.001). The combined PT‐LN framework had 3‐year DFS and OS AUCs of 0.798 and 0.818, with modest gains over LN‐only classification.  Conclusions: Residual nodal disease despite primary‐tumor MPR identifies an adverse phenotype with predominantly regional nodal recurrence. The combined framework is an interpretable stratification approach requiring external validation; surveillance and treatment implications remain hypothesis‐generating.
SN  - 2045-7634
ER  -