This is a single-arm, single-center, open-label, observational clinical study. A total of 30 patients with initially unresectable locally advanced esophageal squamous cell carcinoma will be enrolled.Eligible patients will receive albumin-bound paclitaxel (260 mg/m², day 1, every 3 weeks [Q3W]) plus cisplatin (75 mg/m²) or carboplatin (AUC = 5), in combination with tislelizumab (200 mg, day 2, Q3W), for 2-4 cycles. Tumor staging will be reassessed thereafter, and the feasibility of surgical resection will be determined based on multidisciplinary team (MDT) discussion.The primary endpoint is the conversion rate to surgery.

Secondary endpoints include pathological complete response (pCR), objective response rate (ORR), and safety.

Inclusion Criteria:

1. Written informed consent is obtained prior to any study-related procedures.

2. Age 18 to 75 years, inclusive; both male and female patients are eligible.

3. Histologically and radiologically confirmed thoracic esophageal squamous cell carcinoma (ESCC) with initially unresectable locally advanced disease, defined as:

   T4b tumors invading adjacent critical structures, including the heart, great vessels, trachea, or other adjacent organs (including liver, pancreas, lung, or spleen); or Multiple-station or bulky lymph node metastases.

4. No evidence of distant metastasis.

5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

7. Estimated life expectancy of ≥6 months.

8. Adequate organ function, as defined below (without transfusion of blood products or use of hematopoietic growth factors within 14 days prior to assessment):

   Hematologic function: absolute neutrophil count (ANC) ≥1,500/mm³; platelet count ≥100,000/mm³; hemoglobin ≥9 g/dL (5.6 mmol/L).

   Renal function: serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min.

   Hepatic function: total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤1.5 × ULN.

9. For women of childbearing potential: must have a negative serum or urine pregnancy test within 7 days prior to enrollment, must not be breastfeeding, and must agree to use a medically acceptable method of contraception (e.g., intrauterine device, oral contraceptives, or barrier methods) during the study treatment period and for at least 3 months after the last dose.

   For men with partners of childbearing potential: must agree to use a medically acceptable method of contraception during the study treatment period and for at least 3 months after the last dose.

10. Willingness to participate in the study, good compliance, and ability to adhere to study procedures, including safety and survival follow-up.

Exclusion Criteria:

1. Prior receipt of radiotherapy, chemotherapy, hormonal therapy, surgery, or molecular targeted therapy for esophageal cancer.

2. Evidence of distant metastasis confirmed by imaging.

3. History of other malignancies, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.

4. Prior treatment with any anti-PD-1 or anti-PD-L1 agents; known hypersensitivity to monoclonal antibodies or any component of tislelizumab.

5. Active autoimmune disease or a history of autoimmune disease, including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.

6. Patients with vitiligo or a history of childhood asthma that has completely resolved and requires no intervention in adulthood may be eligible.

7. Patients with asthma requiring bronchodilator therapy are not eligible.

8. Current use of immunosuppressive medications, including systemic corticosteroids or absorbable local steroids for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.

   Clinically significant ascites or pleural effusion requiring therapeutic drainage.

   Uncontrolled or clinically significant cardiovascular disease, including but not limited to:

   New York Heart Association (NYHA) class II or higher heart failure; Unstable angina; Myocardial infarction within 1 year prior to enrollment; Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.

9. Coagulation abnormalities, defined as: prothrombin time (PT) >16 seconds, activated partial thromboplastin time (APTT) >43 seconds, thrombin time (TT) >21 seconds, or fibrinogen (Fbg) >2 g/L; or presence of bleeding tendency, or ongoing thrombolytic or anticoagulant therapy.

10. Presence of gastrointestinal conditions associated with a high risk of bleeding or perforation within 3 months prior to enrollment, including but not limited to esophageal varices, active gastric or duodenal ulcers, ulcerative colitis, portal hypertension, or unresected tumors with active bleeding; or any other condition judged by the investigator to pose a risk of gastrointestinal bleeding or perforation.

Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma