ctDNA After Oesophagal Cancer Surgery: Annals of Surgery | August 2026

Introduction:

Despite neoadjuvant chemotherapy and curative resection, 40–60% of patients with locally advanced oesophagal squamous cell carcinoma (ESCC) ultimately develop recurrence. Conventional imaging and pathological response assessment may fail to identify microscopic residual disease. This prospective study evaluated whether personalised, tumour-informed circulating tumor DNA (ctDNA) can identify patients at high risk of recurrence during treatment and surveillance.

Why was this study needed?

Reliable biomarkers for recurrence after curative ESCC surgery remain limited.

ctDNA can detect molecular residual disease (MRD) before it becomes radiologically apparent.

Serial testing could potentially refine postoperative risk beyond conventional staging and pathology.

ESCC-specific prospective data have been relatively scarce.

Results:

Among 28 evaluable patients, post-neoadjuvant ctDNA positivity was associated with substantially higher recurrence (77.8% vs 27.8%) and worse RFS (HR 4.56).

During the postoperative MRD window, 100% of ctDNA-positive patients recurred, compared with 30.4% of ctDNA-negative patients.

Postoperative ctDNA positivity was an exceptionally strong predictor of recurrence (HR 30.99).

Detectable ctDNA during subsequent surveillance remained strongly associated with recurrence (HR 27.34).

Clinical Impact:

The most clinically relevant time point appears to be after curative surgery. A positive ctDNA result may identify a population with persistent molecular disease despite apparently successful resection and negative conventional imaging.

This creates a potential future pathway:

NAC → surgery → postoperative ctDNA → MRD-guided adjuvant therapy/intensified surveillance.

Conversely, persistently negative ctDNA might eventually help identify patients suitable for less intensive treatment or surveillance—but this study is far too small to establish such de-escalation.

Important Limitation:

The effect sizes are striking, but only 28 patients were evaluable. This is a prospective observational biomarker study, not evidence that changing treatment according to ctDNA improves survival. Larger prospective interventional trials are essential.

Bottom Line:

Postoperative ctDNA positivity identified an extremely high-risk ESCC population: every MRD-positive patient in this small cohort developed recurrence. ctDNA could become a powerful tool for postoperative risk stratification, but the next critical step is proving that ctDNA-guided intervention actually improves patient outcomes.