Neoadjuvant Chemoradiotherapy Plus Surgery vs. Surgery Plus Adjuvant Therapy for ESCC

• 1. Aged 18 to 75 years, both sexes; 2. Histologically confirmed locally advanced (cT1N+M0 or T2-4aNxM0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM stage); 3. Cervical contrast-enhanced CT showed no suspicious metastatic lymph nodes, and imaging studies confirmed no systemic metastasis; 4. Expected to achieve R0 resection; 5. ECOG performance status 0 to 1; 6. No prior antitumor therapy for esophageal cancer, including chemotherapy, radiotherapy (including planned radiotherapy during the study), hormone therapy, or immunotherapy; 7. Measurable lesions according to RECIST v1.1 criteria; 8. No contraindications for surgery based on preoperative evaluation of organ function; 9. Laboratory test results confirm eligibility:

     • Hemoglobin ≥90 g/L;
     • White blood cell count ≥ the laboratory lower limit of normal;
     • Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
     • Platelet count ≥100×10⁹/L;
     • Total bilirubin ≤1.5× upper limit of normal (ULN);
     • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN;
     • Prothrombin time ≤16 seconds and international normalized ratio (INR) ≤1.5× ULN;
     • Serum creatinine ≤1.5× ULN or creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula); 10. Women of childbearing potential must agree to use effective contraception (e.g., intrauterine devices, oral contraceptives, or condoms) during the study medication period and for 60 days after the last dose, have a negative serum pregnancy test within 7 days prior to enrollment, and must not be lactating; 11. Men must agree to use effective contraception during the study medication period and for 60 days after the last dose; 12. Participants must understand and sign the informed consent form.

Exclusion Criteria:

• 1. History of Other Malignancies: 1.1. Patients who have had malignancies other than esophageal cancer.

     2. Bleeding Tendency and Coagulation Disorders: 2.1. Gastrointestinal bleeding within 6 months prior to randomization. 2.2. Coagulation disorders at the time of enrollment. 2.3. Patients receiving thrombolysis or anticoagulant therapy.
     3. Cardiovascular and Cerebrovascular Diseases: 3.1. The following conditions within 12 months prior to randomization:
     • Congestive heart failure classified as NYHA class II or higher.
     • Unstable angina, myocardial infarction, or poorly controlled arrhythmias.
     • Cerebrovascular accidents. 3.2. Left ventricular ejection fraction (LVEF) \<50% on echocardiography. 3.3. Corrected QT interval (QTc) >480 ms (calculated using the Fridericia formula; if QTc is abnormal, three consecutive tests should be conducted at 2-minute intervals, and the average value used).

3.4. Medically difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg) based on the average of at least two measurements.

3.5. History of hypertensive crises or hypertensive encephalopathy.

4. Respiratory Diseases: 4.1. History of interstitial lung disease or pneumonia requiring steroid treatment at enrollment.

4.2. Active tuberculosis at the time of randomization or anti-tuberculosis treatment within 1 year prior to randomization.

4.3. Asthma requiring intermittent bronchodilators or other medical interventions at randomization.

5. Infectious and Inflammatory Diseases: 5.1. Patients with active hepatitis B must receive effective treatment before enrollment.

5.2. For patients positive for HCV antibodies, HCV-RNA testing should exclude those with HCV-RNA >10³ copies/mL.

5.3. Co-infection with HIV.

6. Surgery-Related Risks: 6.1. Severe unhealed wounds, active ulcers, or untreated fractures at the time of randomization.

6.2. Other conditions rendering the patient inoperable. 6.3. Prior surgeries that preclude using the stomach for esophageal reconstruction during this surgery.

7. Drug and Treatment-Related Risks: 7.1. Receiving systemic steroid therapy (daily prednisone >10 mg or equivalent) or other immunosuppressive agents within 2 weeks before randomization.

7.2. Severe allergy to chemotherapy drugs. 7.3. Previous organ transplant recipients.

8. Liver Function Requirements: 8.1. For patients with HBsAg(+) and/or HBcAb(+), HBV DNA must be \<500 IU/mL with normal liver function.

8.2. Continued effective anti-HBV therapy during the study or initiation of entecavir or tenofovir treatment prior to study medication.

9. Other Conditions: 9.1. Severe unhealed wounds, active ulcers, or untreated fractures at the time of randomization.

9.2. Any condition deemed unsuitable for study participation by the investigator.