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Published on: August 24, 2017
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Preoperative Circulating Tumor DNA Detection and Risk Stratification in Esophageal Squamous Cell Carcinoma
Tae Hee Hong1, Jun-Gi Jeong2, Seong Yong Park3
1Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
JAMA Surgery
|February 18, 2026
Summary
Preoperative circulating tumor DNA (ctDNA) detection in esophageal squamous cell carcinoma (ESCC) is linked to higher nodal metastasis and recurrence risk. This blood test may improve risk stratification for early-stage ESCC, guiding personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Current criteria for neoadjuvant chemoradiotherapy in clinical stage II (T2N0) esophageal squamous cell carcinoma (ESCC) have limited predictive value.
- There is a need for improved preoperative risk stratification tools to guide treatment decisions in early-stage ESCC.
Purpose of the Study:
- To investigate the association between preoperative circulating tumor DNA (ctDNA) detection and nodal upstaging and postoperative recurrence in patients with clinical stage I (T1b) or T2N0 ESCC.
- To evaluate ctDNA as a potential biomarker for risk stratification in early-stage ESCC.
Main Methods:
- A cohort study involving two independent cohorts (Samsung Medical Center and Yonsei University Severance Hospital) of patients with T1b or T2N0 ESCC.
- Tumor-informed ctDNA sequencing was performed on preoperative plasma samples.
- Analysis included logistic regression and Cox proportional hazard models to assess associations between ctDNA status, nodal metastasis, and survival outcomes (recurrence-free survival and overall survival).
Main Results:
- Preoperative ctDNA was detected in 48.6% of patients and was significantly associated with worse recurrence-free survival (HR, 4.15) and overall survival (HR, 4.02).
- In patients with T2N0 ESCC, ctDNA positivity predicted occult nodal metastasis with high accuracy (PPV 100% in SMC, 88.89% in YUSH).
- Preoperative ctDNA outperformed guideline-based criteria (tumor size, LVI, poor differentiation) in predicting nodal metastasis and improved risk stratification models.
Conclusions:
- Preoperative ctDNA detection is significantly associated with occult nodal metastasis and recurrence risk in clinical N0 early-stage ESCC.
- ctDNA shows potential as a complementary biomarker for risk stratification in T2N0 ESCC, aiding in neoadjuvant treatment decisions and personalized therapy.
- Incorporating ctDNA into risk assessment models enhances their predictive accuracy for early-stage ESCC.

