This is a prospective, single-center, randomized phase 2 study of adebrelimab plus full-course neoadjuvant therapy in resectable locally advanced esophageal squamous cell carcinoma. Patients achieving clinical complete response (cCR) after neoadjuvant treatment will be randomized 1:1 to watchful waiting with 2 cycles consolidation chemo-Immunotherapy or standard surgery. Primary endpoint is 2-year DFS. Secondary endpoints include OS, pCR/MPR, R0 resection rate, safety, and quality of life.

Inclusion Criteria:

• Patients voluntarily participate in this study, sign an informed consent form, and demonstrate good compliance;

• At least 18 years of age; gender is not restricted;

• ECOG performance status: 0-1;

• Patients with histologically confirmed resectable esophageal squamous cell carcinoma clinically staged as (T1N+M0 or T2-4aNanyM0);

• No prior anticancer therapy for esophageal cancer, including chemotherapy, hormone therapy, radiation therapy, or immunotherapy;

• Laboratory tests must meet the following criteria (within 7 days prior to baseline enrollment):

  1. Complete blood count (CBC):

     1. Hemoglobin (Hb) ≥ 90 g/L (no blood transfusion within the past 14 days);
     2. Neutrophil count (NEUT) ≥ 1.5 × 10⁹/L;
     3. Platelet count (PLT) ≥ 100 × 10⁹/L;
     4. White blood cell count (WBC) ≥ 3 × 10⁹/L;

  2. Biochemical Tests:

     1. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×ULN;
     2. Serum total bilirubin (TBIL) ≤ 1.5×ULN;
     3. Serum creatinine (Cr) ≤ 1.5×ULN; (or creatinine clearance (CCr) ≥ 60 mL/min);

  3. Coagulation function: Activated partial thromboplastin time (APTT), International Normalized Ratio (INR), and prothrombin time (PT) ≤ 1.5×ULN;

  4. Thyroid function: Thyroid-stimulating hormone (TSH) ≤ ULN (if abnormal, FT3 and FT4 levels should also be evaluated; if FT3 and FT4 levels are normal, the patient may be enrolled);

  5. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%;

• Female participants must agree to use contraceptive measures, such as an intrauterine device (IUD), oral contraceptives, or condoms, during the study and for 6 months after study completion; they must have a negative serum pregnancy test within 7 days prior to study enrollment and must not be breastfeeding; male participants must agree to use contraceptive measures during the study and for 6 months after study completion.

Exclusion Criteria:

• Concurrent malignant neoplasms (except for cured basal cell carcinoma of the skin);

• Diagnosis of cervical esophageal cancer;

• History of severe hypersensitivity reactions following administration of other monoclonal antibodies;

• Presence of any active autoimmune disease or history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, or nephritis; asthma requiring bronchodilators for medical intervention); however, the following patients are eligible for enrollment: vitiligo, psoriasis, or alopecia not requiring systemic treatment; well-controlled type 1 diabetes; hypothyroidism with normal thyroid function following replacement therapy;

• Requiring immunosuppressants, or systemic or absorbable topical corticosteroids for immunosuppressive purposes (dose > 10 mg/day of prednisone or other corticosteroids of equivalent potency), and still using them within 2 weeks of the first dose;

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;

• Uncontrolled symptoms of brain metastases, spinal cord compression, or carcinomatous meningitis occurring within 4 weeks prior to the first dose, or patients with brain or meningeal disease identified by CT or MRI at screening;

• Patients with any severe and/or uncontrolled medical conditions, including:

  1. Acute or recurrent myocardial ischemia or myocardial infarction; poorly controlled and clinically significant arrhythmias; and heart failure of Class II or higher (New York Heart Association [NYHA] functional class); LVEF (left ventricular ejection fraction) < 50%;
  2. Active or uncontrolled severe infection (≥ Grade 2 CTC AE infection);

• Receipt of a prophylactic or attenuated vaccine within 4 weeks prior to the first dose;

• Other factors, as determined by the investigator, that may lead to forced discontinuation of the study, such as other serious illnesses (including psychiatric disorders) requiring concomitant treatment, severe laboratory abnormalities, or family or social factors that could compromise the subject's safety.

• If HBsAg (+) and/or HBcAb (+), HBV DNA must be < 500 IU/mL (if the local center's lower limit of detection is higher than 500 IU/mL, the investigator may decide on enrollment based on specific circumstances) and the subject must continue to receive effective anti-HBV therapy during the study, or must have already started treatment with entecavir or tenofovir prior to study drug administration;

• If HCV antibodies are positive, HCV-RNA testing must be performed; subjects with HCV-RNA > 10³ copies/mL must be excluded;

• HIV-positive.