Through a prospective, single-center, single-arm, phase Ib/II study, we aim to explore the safety and feasibility of a new treatment mode for upper esophageal cancer, which is that pembrolizumab combined with chemoradiotherapy as neoadjuvant therapy and then followed by radical surgery.

Treatment includes induction treatment, sequential treatment and maintenance treatment.

1. Preoperative neoadjuvant therapy 1) Induction therapy (2 cycles): Immunotherapy+Chemotherapy Pembrolizumab 200mg, IV, D1, q3w, Albumin paclitaxel, 125mg/m2, IV, D1/D8, q3w; Cisplatin, 70mg/m2 in total, IV, given in three times, q3w. 2) Sequential treatment: Immunotherapy+Chemoradiotherapy Pembrolizumab 200mg, IV, D1, q3w, 2 cycles; Albumin paclitaxel, 100mg, IV, D1, QW, 4 cycles; Cisplatin, 20mg/m2, IV, D1, QW, 4 cycles. Radiotherapy: PTV: 44gy/2gy/22fx, 5 days a week, 5 weeks in total.
2. Surgery 4-8 weeks after the end of the neoadjuvant therapy, the operation can be performed only when the indexes of leukocyte, platelet, liver and kidney function of the patient are normal. The operation aims to achieve R0 resection with laryngeal preservation.
3. Postoperative adjuvant treatment Patients who did not reach pCR after operation were given pembrolizumab 200mg, IV, D1, q3w 4-6 weeks after operation until 1 year, disease progression or intolerable toxicity.
4. Follow-up period Patients will be continuously monitored during the study. The enrolled subjects will be closely followed up for 2 years.

Inclusion Criteria:

1. Sign the informed consent form before enrollment;
2. Be aged 18-80 years old, and be male or female;
3. Have potentially upper ESCC (upper edge of tumor ≤ 5cm from esophageal entrance) diagnosed with cT1-3N1-2M0 or cT2-3N0M0 (AJCC 8th);
4. Have an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
5. No previous treatments;
6. Be eligible for R0 resection before treatment;
7. Demonstrate adequate organ function; all screening laboratory tests will be performed within 10 days of treatment initiation;
8. Have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication if they are a female subject with childbearing potential. 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 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 the initiation of treatment on Day 10. Subjects for whom newly obtained samples cannot be provided (e.g., as newly obtained sample is inaccessible or due to subject safety concerns) may submit an archived specimen, but only with the agreement of the sponsor;

11. Be expected to survive >6 months; 12. Join the clinical study on a completely voluntary basis, demonstrate good adherence, and cooperate with the follow-up assessments for safety and survival

Exclusion Criteria:

1. Have undergone any previous therapy (e.g., an operation, radiotherapy, immunotherapy, or chemotherapy) for ESCC;
2. Have a history of other malignant tumor;
3. Be ineligible or have a contraindication for esophagectomy;
4. Have a history of other anti-PD-1/PD-L1 therapies, or have a known history of an allergy to macromolecular protein preparations or any component of PD-1;
5. Have a diagnosis of immunodeficiency or have received chronic systemic steroid therapy (in doses >10 mg daily of a prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of the study drug;
6. Have an active autoimmune disease that required systemic treatment in the past 2 years (e.g., the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs);
7. Have poorly controlled cardiac symptoms or cardiac diseases;
8. Have a history or evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severely impaired lung function.