Adaptive Neoadjuvant Therapy for Esophageal Cancer

Inclusion Criteria: Inclusion criteria for esophageal cancer: 1. Histologically or cytologically confirmed thoracic esophageal squamous cell carcinoma (ESCC) at stages T1-4aN1-3M0 or T3-4aN0M0 (AJCC 9th edition); Neck color Doppler ultrasound shows no suspicious metastatic lymph nodes. Note: For the determination of T staging, CT combined with MRI or endoscopic ultrasound is used. Research centers are encouraged to use endoscopic ultrasound; Research centers are encouraged to obtain tissue confirmation of lymph node involvement, provided that it can be safely obtained through puncture, EBUS (endobronchial ultrasound), EUS (endoscopic ultrasound) or mediastinoscopy. However, when the boundaries of the lymph nodes are clear and the shortest axis diameter of at least one lymph node is ≥ 2.0 cm, lymph node involvement can be determined by imaging examination (MRI/CT scan); M1 is excluded in FDG-PET/CT or diagnostic-quality CT or MRI scans of the chest, abdomen, pelvis and brain. 2. The lesion is a potentially resectable thoracic esophageal lesion. 3. R0 resection is expected to be achieved. 4. No previous treatment for esophageal tumors has been received. General inclusion requirements: 1. Sign the informed consent form. 2. Male or female aged ≥ 18 years and ≤ 75 years. 3. ECOG performance status is 0 or 1. 4. There are no surgical contraindications based on the evaluation of various organ function tests before surgery. 5. Body weight is greater than 35 kg; The weight loss in the past three months does not exceed 10%. 6. The expected survival time is more than 12 months. 7. Agree to provide previously stored tumor tissue specimens or undergo a biopsy to collect tumor lesion tissue for biomarker analysis. 8. According to the RECIST 1.1 criteria, there is at least one measurable lesion. 9. Good organ function: A.Hematology: White blood cell count ≥ 4×10⁹/L Neutrophil count ≥ 2×10⁹/L Hemoglobin ≥ 9 g/dL Platelet count ≥ 100×10⁹/L B.Liver function: Bilirubin ≤ 1.5 times the upper limit of normal (ULN). Patients with known Gilbert's disease and a serum bilirubin level ≤ 3 times ULN may be eligible for enrollment. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN. In case of liver metastasis, AST/ALT ≤ 5 times ULN. Alkaline phosphatase (ALP) ≤ 3 times ULN. In case of liver or bone metastasis, ALP ≤ 5 times ULN. Albumin ≥ 3 g/dL International Normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times ULN C.Renal function: Serum creatinine ≤ 1.5 times ULN or creatinine clearance rate ≥ 60 mL/min calculated by the Cockcroft - Gault formula Exclusion Criteria: Cancer - specific exclusion criteria: 1. Cervical esophageal cancer. Patients whose clinical stage is determined to be stage I/IIA, unresectable stage T4b, or with distant metastasis (M1) through imaging examinations such as enhanced chest - abdomen CT, cervical lymph node ultrasound, whole - body PET - CT, or EBUS (optional). 2. Patients with a history of malignancies other than esophageal cancer within 5 years, except for malignancies with negligible risk of metastasis or death (e.g., expected 5 - year overall survival rate \> 90%) and those expected to be cured after treatment, such as appropriately treated cervical carcinoma in situ, basal or squamous cell skin cancer, limited prostate cancer treated with radical surgery, and ductal carcinoma in situ treated with radical surgery. General medical exclusion criteria: 1. Women who are pregnant, breastfeeding, or planning to become pregnant during the study period. 2. Patients with a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug - induced pneumonia, idiopathic pneumonia, or evidence of active pneumonia detected by chest CT scan during screening. 3. Significant cardiovascular diseases, such as heart diseases defined by the New York Heart Association (class II or higher), myocardial infarction occurring within 3 months before enrollment, unstable arrhythmia, unstable angina pectoris. Patients known to have coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must receive the optimal stable treatment plan determined by the attending physician, and consultation with a cardiologist can be carried out if necessary. 4. Patients with active hepatitis B (chronic or acute; defined as positive hepatitis B surface antigen (HBsAg) test result during screening and HBV DNA copy number \> 1000 cps/ml) or hepatitis C: 5. Patients with a history of hepatitis B virus (HBV) infection or those with cured HBV infection (defined as positive hepatitis B core antibody (HBcAb) and negative HBsAg) may be eligible for this study. Before random assignment, HBV deoxyribonucleic acid (DNA) testing must be performed on such patients, and they are only eligible to participate in the study if HBV DNA is negative (HBV DNA \< 1000 cps/ml). 6. Among patients with positive hepatitis C virus (HCV) antibody, only those with negative polymerase chain reaction (PCR) HCV ribonucleic acid (RNA) can participate in this study. 7. Patients with active pulmonary tuberculosis (clinical diagnosis includes clinical history, physical examination, imaging findings, and TB examinations according to local medical routines). 8. Patients with a positive human immunodeficiency virus (HIV) test result. 9. Patients with severe uncontrolled systemic intermittent diseases, such as active infections or poorly controlled diabetes. 10. Patients with abnormal blood coagulation function, bleeding tendency (such as active peptic ulcer), or those receiving thrombolytic or anticoagulant therapy. 11. Patients with existing or co - existing hemorrhagic diseases. 12. Patients with peripheral nervous system disorders or a history of significant mental disorders and central nervous system disorders. 13. Patients who, due to previous surgeries, cannot use the stomach to replace the esophagus for digestive tract reconstruction in this surgery. Treatment - related exclusion criteria: 1. Patients who have received any approved anti - cancer treatment (including radiotherapy, chemotherapy, hormone therapy, or traditional Chinese medicine) before starting the study treatment. 2. Patients who have received other investigational drugs or participated in other therapeutic clinical studies within 28 days before enrollment; this includes signing the informed consent form (ICF) for other trials, and patients who failed screening are also not eligible for enrollment. 3. Patients who have previously received immune checkpoint blockade therapy, such as treatment with anti - programmed death receptor - 1 (anti - PD - 1) and anti - PD - L1 therapeutic antibodies. 4. Patients who have received systemic immunostimulants within 4 weeks before random assignment or within 5 drug half - lives (t1/2) (whichever is longer) \[including but not limited to interferon (IFN) or interleukin - 2\]; vaccination with cancer vaccines is allowed in previous treatments. 5. Patients who have received systemic immunosuppressive drugs (\> 10 mg/d prednisone equivalent) within 2 weeks before random assignment, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti - tumor necrosis factor (TNF) drugs: 6. For patients who have received short - term, low - dose, systemic immunosuppressive treatment (for example, a single dose of dexamethasone for nausea), they may participate in this study after consultation between the investigator and the medical monitor and approval by the medical monitor. 7. Patients using inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease, patients using mineralocorticoids (such as fludrocortisone) for the treatment of orthostatic hypotension, and patients using low - dose glucocorticoid supplements (≤10mg /d prednisone or equivalent) for the treatment of adrenal cortical insufficiency are eligible for enrollment. 8. Patients with a history of allergic reactions to platinum - containing compounds or taxanes. 9. Other situations determined by the principal investigator (PI) or attending physician as inappropriate for enrollment.