Extent of lymphadenectomy dictates adjuvant chemotherapy benefit in primarily resected esophageal squamous cell carcinoma: a multi-cohort validation
5 affiliations
- 1Department of Thoracic Surgery, Fujian Medical University Union Hospital
- 2Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University)
- 3Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education
- 4Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University
- 5Clinical Research Center for Thoracic Tumors of Fujian Province, Fujian Medical University
Abstract
Background: While primary surgery remains a crucial treatment for resectable esophageal squamous cell carcinoma (ESCC), the uniform application of postoperative adjuvant chemotherapy for pathologically node-positive patients exposes many to severe systemic toxicity. This study hypothesizes the existence of a specific lymph node dissection (LND) threshold that stratifies the survival benefit of adjuvant chemotherapy and aims to define this cutpoint to enable safe therapeutic de-escalation.
Methods: We conducted a multi-cohort retrospective study using data from the Surveillance, Epidemiology, and End Results (SEER) database (n = 753, training cohort) and a Chinese single-center repository (n = 447, validation cohort) of patients with ESCC who underwent primary radical esophagectomy without radiotherapy. The optimal prognostic cutpoint for LND was mathematically determined using X-tile software. An interactive Cox proportional hazards nomogram incorporating an LND-by-chemotherapy interaction term was developed and validated. Subsequently, layer-specific 1:1 propensity score matching (PSM) was performed within separate surgical strata of the validation cohort to assess chemotherapy efficacy.
Results: X-tile analysis established 21 lymph nodes as the optimal LND threshold. Multivariable analysis confirmed that adequate LND (≥ 21 nodes) and adjuvant chemotherapy were independent protective prognostic factors. The interactive nomogram demonstrated good discrimination and calibration across both populations. Crucially, layer-specific PSM in the external validation cohort revealed divergent therapeutic responses dependent on surgical quality. For patients with suboptimal LND (< 21 nodes), adjuvant chemotherapy provided a significant survival benefit over surgery alone (P = 0.048). In contrast, for patients achieving an adequate LND (≥21 nodes), the addition of adjuvant chemotherapy yielded no further survival advantage (P = 0.085).
Conclusions: Achieving the removal of ≥ 21 lymph nodes serves as a robust anatomical biomarker that fundamentally alters the postoperative therapeutic landscape for ESCC. Patients with suboptimal LND require adjuvant chemotherapy to compensate for potential residual disease, whereas those achieving the 21-node clearance threshold derive no additional survival benefit from systemic interventions and can be safely exempted from cytotoxic over-treatment.
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BibTeX
@article{huang2026extent,
title = {{Extent of lymphadenectomy dictates adjuvant chemotherapy benefit in primarily resected esophageal squamous cell carcinoma: a multi-cohort validation}},
author = {Yicheng Huang and Xuanhao Lin and Yanhong Lin and Ziyang Han},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1920549},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1920549/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extent of lymphadenectomy dictates adjuvant chemotherapy benefit in primarily resected esophageal squamous cell carcinoma: a multi-cohort validation
AU - Yicheng Huang
AU - Xuanhao Lin
AU - Yanhong Lin
AU - Ziyang Han
PY - 2026
DA - 2026/10/29
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1920549
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1920549/full
AB - Background: While primary surgery remains a crucial treatment for resectable esophageal squamous cell carcinoma (ESCC), the uniform application of postoperative adjuvant chemotherapy for pathologically node-positive patients exposes many to severe systemic toxicity. This study hypothesizes the existence of a specific lymph node dissection (LND) threshold that stratifies the survival benefit of adjuvant chemotherapy and aims to define this cutpoint to enable safe therapeutic de-escalation. Methods: We conducted a multi-cohort retrospective study using data from the Surveillance, Epidemiology, and End Results (SEER) database (n = 753, training cohort) and a Chinese single-center repository (n = 447, validation cohort) of patients with ESCC who underwent primary radical esophagectomy without radiotherapy. The optimal prognostic cutpoint for LND was mathematically determined using X-tile software. An interactive Cox proportional hazards nomogram incorporating an LND-by-chemotherapy interaction term was developed and validated. Subsequently, layer-specific 1:1 propensity score matching (PSM) was performed within separate surgical strata of the validation cohort to assess chemotherapy efficacy. Results: X-tile analysis established 21 lymph nodes as the optimal LND threshold. Multivariable analysis confirmed that adequate LND (≥ 21 nodes) and adjuvant chemotherapy were independent protective prognostic factors. The interactive nomogram demonstrated good discrimination and calibration across both populations. Crucially, layer-specific PSM in the external validation cohort revealed divergent therapeutic responses dependent on surgical quality. For patients with suboptimal LND (< 21 nodes), adjuvant chemotherapy provided a significant survival benefit over surgery alone (P = 0.048). In contrast, for patients achieving an adequate LND (≥21 nodes), the addition of adjuvant chemotherapy yielded no further survival advantage (P = 0.085). Conclusions: Achieving the removal of ≥ 21 lymph nodes serves as a robust anatomical biomarker that fundamentally alters the postoperative therapeutic landscape for ESCC. Patients with suboptimal LND require adjuvant chemotherapy to compensate for potential residual disease, whereas those achieving the 21-node clearance threshold derive no additional survival benefit from systemic interventions and can be safely exempted from cytotoxic over-treatment.
SN - 2234-943X
ER -