A Non-inferiority Study of Indocyanine Green-guided Sentinel Lymph Node Mapping Versus Conventional Lymph Node Dissection in Esophageal Cancer

This study will enroll patients with cT1-3N0M0 esophageal cancer who have not received neoadjuvant therapy. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomly assigned into two groups: the experimental group will undergo sentinel lymph node dissection only plus esophagectomy, while the control group will undergo conventional lymph node dissection plus esophagectomy. The investigators will compare the 3-year disease-free survival rate, postoperative complication rate, and other outcomes between the two groups to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.

• ICG-guided sentinel lymph node dissection (Drug): In the experimental group, the investigators will perform only sentinel lymph node dissection and esophagectomy, without further lymph node resection. This intervention is distinguished by its de-escalated surgical approach: unlike conventional radical esophagectomy with systematic lymph node dissection, no additional lymph node stations will be removed beyond the identified sentinel lymph nodes. By preserving non-sentinel regional lymph nodes, this strategy aims to reduce surgical trauma and postoperative complications-such as chylothorax and recurrent laryngeal nerve injury-while maintaining oncological safety in patients with cT1-3N0M0 esophageal squamous cell carcinoma.
• ICG-guided systematic lymph node dissection (Drug): In the control group, in addition to dissecting the sentinel lymph nodes, the investigators will proceed with standard two-field or three-field lymph node dissection for esophageal cancer.

Primary outcomes

• 3-year Disease free survival rate [The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 months.]: 3-year disease-free survival rate: defined as the time from randomization to the first occurrence of any of the following events: local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause

Secondary outcomes

• Postoperative complications [30 days after surgery]: The incidence of severe complications with Clavien-Dindo grade ≥ III within 30 days after surgery; the incidence of specific complications such as chylothorax, recurrent laryngeal nerve injury, anastomotic leakage, and pulmonary infection.
• Immune status indicators [Baseline (day -1), post-operative day 1, day 7, and month 1.]: Immune status indicators: changes in peripheral blood lymphocyte subsets (CD4+, CD8+, NK cells) counts before and after surgery.
• lmmune status indicators [Baseline (day -1), post-operative day 1, day 7, and month 1.]: lmmune status indicators: changes in peripheral blood lymphocyte subsets (CD4+CD8+, NK cells) rates before and after surgery.
• 3-year Overall Survival rate [3-year after surgery]: 3-year Overall Survival rate
• Diagnostic performance of ICG [7-day after surgery]: Diagnostic performance of ICG (using postoperative routine pathology as the gold standard): sensitivity, specificity, positive predictive value, negative predictive value, and false negative rate of ICG in identifying sentinel lymph nodes.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria

1. Aged 18 to 75 years, regardless of gender;
2. Histopathologically confirmed esophageal squamous cell carcinoma or adenocarcinoma by endoscopic biopsy (including esophagogastric junction carcinoma, Siewert type I/II);
3. Preoperative clinical stage cT1-3N0M0 (based on contrast-enhanced CT ± PET-CT ± endoscopic ultrasound evaluation);
4. No prior neoadjuvant therapy of any form (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, targeted therapy, etc.);
5. Scheduled for minimally invasive radical esophagectomy (combined thoracoscopic and laparoscopic McKeown or Ivor-Lewis procedure);
6. No surgical contraindications, with cardiac, pulmonary, hepatic, and renal functions sufficient to tolerate surgery;
7. ECOG performance status score of 0 to 1;
8. Written informed consent signed by the patient or legal representative.

Exclusion Criteria

1. Preoperative imaging clearly indicating lymph node metastasis (cN+) or distant metastasis (cM1);
2. Prior systemic or local treatment for esophageal cancer of any kind (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, etc.);
3. Previous history of esophageal or gastric surgery (except endoscopic mucosal resection/submucosal dissection);
4. History of allergy to iodine contrast agents or indocyanine green;
5. Severe hepatic or renal insufficiency (Child-Pugh class B or C; serum creatinine ≥ 1.5 times the upper limit of normal);
6. Uncontrolled hyperthyroidism;
7. Concomitant other malignancies requiring simultaneous treatment;
8. Pregnant or lactating women;
9. Other conditions deemed unsuitable for enrollment by the investigator.

Withdrawal Criteria

1. Intraoperative exploration revealing inability to achieve radical resection (R2 resection) or extensive thoracic and abdominal metastasis;
2. Intraoperative exploration revealing definite lymph node metastasis (cN+) inconsistent with preoperative staging;
3. Severe allergic reaction after ICG injection requiring discontinuation of the study;
4. Intraoperative change of surgical plan due to severe complications;
5. Withdrawal of informed consent by the patient.

• Bin Zheng, Principal investigator, Fujian Medical University Union Hospital