Biomarker Based Neoadjuvant Strategies for Locally Advanced Resectable ESCC

Inclusion Criteria: 1. Diagnosis: Histologically confirmed esophageal squamous cell carcinoma (ESCC). 2. Stage: Resectable locally advanced ESCC (clinical stage II-III according to the AJCC/UICC 8th edition). 3. Age: 18-75 years old. 4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 5. PD-L1 Expression: Available PD-L1 expression level (CPS). 6. Surgical Eligibility: Assessed as eligible for surgical resection by a thoracic surgeon. 7. Laboratory Requirements: * Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, Platelets ≥ 100 x 10\^9/L, Hemoglobin ≥ 9 g/dL. * Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN. * Adequate renal function: Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min. 8. Informed Consent: Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: 1. Distant Metastasis: Presence of distant metastasis. 2. Other Malignancies: History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin carcinoma, or other localized non-invasive malignancy. 3. Autoimmune Diseases: History of active autoimmune diseases requiring systemic treatment within the past 2 years. 4. Infections: Active infection requiring systemic therapy. 5. Uncontrolled Conditions: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 6. Previous Treatment: Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies. 7. Pregnancy and Lactation: Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization. 8. Allergies: Known allergy or hypersensitivity to study drugs or any excipient of these medications.