Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002)

Inclusion Criteria: 1. Histologically confirmed esophageal squamous cell carcinoma; 2. R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification); 3. No suspicious metastatic lymph nodes on the clavicle; 4. Have a performance status of 0 or 1 on the ECOG Performance Scale; 5. Age 18-75 years old, both men and women; 6. Be willing and able to provide written informed consent/assent for the trial; 7. Demonstrate adequate organ function ; 8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; 9. Be willing to provide tissue, blood, and urine samples. Tissue should be from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) before initiation of treatment on Day 1. 10. Have not received systemic or local treatment for esophageal cancer in the past. Exclusion Criteria: 1. Ineligibility or contraindication for esophagectomy; 2. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer 3. Active autoimmune disease or history of autoimmune disease; 4. Requiring systemic treatment with either corticosteroids or other immunosuppressive medications; 5. Subjects with a history of symptomatic interstitial lung disease; 6. History of allergy to study drug components; 7. Women must not be pregnant or breast-feeding; 8. Patient has received prior chemotherapy, radiotherapy, target therapy ，and immune therapy for this malignancy or any other past malignancy; 9. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.