Surgery vs. Radical Chemoradiotherapy for Esophageal SCC After Neoadjuvant Immunochemotherapy

A Multicenter, Open-Label, Randomized Controlled Phase III Clinical Trial Comparing Surgery Versus Radical Chemoradiotherapy (Organ Preservation) in Patients With Thoracic Esophageal Squamous Cell Carcinoma Achieving cCR or cPR Following Neoadjuvant Immunochemotherapy

This is a Phase III, multicenter, open-label, randomized controlled trial. The study aims to compare organ preservation versus esophagectomy in patients with locally advanced, resectable thoracic esophageal squamous cell carcinoma (ESCC) who achieve a complete or partial clinical response (cCR/cPR) following neoadjuvant immunochemotherapy.

Inclusion Criteria:

1. Age 18-75 years, any sex.

2. ECOG Performance Status 0-1.

3. Histologically confirmed, previously untreated thoracic esophageal squamous cell carcinoma (ESCC).

4. Clinical stage cT2N0M0, T3N0-2M0 (AJCC 8th Edition), assessed as resectable with a potential for R0 resection by endoscopic ultrasound (EUS), PET-CT, and contrast-enhanced CT. Patients with cervical lymph node metastasis may also be included if deemed suitable for three-field lymphadenectomy by a multidisciplinary team assessment.

5. Adequate bone marrow, hepatic, and renal function:

   • Absolute neutrophil count ≥ 1.5 × 10⁹/L, Platelet count ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L.
   • Alanine aminotransferase / Aspartate aminotransferase ≤ 2.5 × Upper Limit of Normal, Total bilirubin ≤ 1.5 × Upper Limit of Normal.
   • Serum creatinine ≤ 1.5 × Upper Limit of Normal or Creatinine clearance ≥ 60 mL/min.

6. Signed written informed consent form (ICF).

Exclusion Criteria:

1. History of other malignancy within the past 5 years.
2. Active autoimmune disease.
3. Active Hepatitis B Virus (HBV) / Hepatitis C Virus (HCV) / Human Immunodeficiency Virus (HIV) infection.
4. Severe cardiac or pulmonary insufficiency (Left Ventricular Ejection Fraction < 50%, Forced Expiratory Volume in 1 second < 1 L).
5. Pregnancy or lactation.