Inclusion Criteria:
1. Age range: 18-70 years, both male and female.
2. Patients with histopathological diagnosis of esophageal squamous cell carcinoma confirmed by gastroscopy/ultrasound gastroscopy, and clinical diagnosis of cT2N1-2M0 or cT3N0-2M0, with TNM staging of stage II-III B.
3. Non-cervical esophageal cancer patients.
4. No prior systemic or local treatment for esophageal cancer, with at least one measurable lesion for imaging evaluation of neoadjuvant therapy according to RECIST 1.1 criteria.
5. ECOG PS (Eastern Cooperative Oncology Group Performance Status): 0-1.
6. Estimated survival period ≥12 months.
7. Subjects without significant dysfunction of major organs, with normal assessment of thyroid, lung, liver, kidney, and cardiac function.
8. Reproductive-age women must have taken reliable contraceptive measures or undergone pregnancy testing (serum or urine) within 7 days prior to enrollment, with negative results, and be willing to use appropriate contraception during the trial and for 8 weeks after the last administration of the investigational drug. For males, they must agree to use appropriate contraception during the trial and for 8 weeks after the last administration of the investigational drug, or have undergone surgical sterilization.
9. Subjects voluntarily participate in this study, sign an informed consent form, demonstrate good compliance, adhere to the planned schedule for regular clinical follow-up and necessary treatment, and cooperate in obtaining regular blood and tissue samples.
Exclusion Criteria:
1. Patients who have had or currently have other malignant tumors within the past 1.5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invades lamina propria)\].
2. Patients with ulcerative esophageal squamous cell carcinoma.
3. Patients with esophageal fistula or tracheal fistula.
4. Patients allergic to anlotinib, toripalimab, or albumin-bound paclitaxel.
5. Patients with a history of immunodeficiency diseases, including HIV-positive patients or those with other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
6. Patients with severe and/or uncontrolled diseases are excluded from the study, including:
6.1 Patients with unsatisfactory blood pressure control (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mmHg).
6.2 Patients with grade I or higher myocardial ischemia or myocardial infarction.
6.3 Patients with arrhythmia (including QT interval ≥480 ms) and grade I heart failure.
6.4 Patients with poorly controlled diabetes (fasting blood glucose \>10 mmol/L) or receiving high-dose glucocorticoid therapy.
6.5 Patients with active or uncontrolled severe infections. 6.6 Patients with decompensated liver disease, active hepatitis B (HBV-DNA ≥10\^4 copies/ml or 2000 IU/ml), or hepatitis C (positive for hepatitis C antibodies and HCV RNA) exceeding the lower limit of the analytical method.
6.7 Patients with hyperthyroidism or hypothyroidism. 6.8 Patients with active tuberculosis.
7. Unresolved toxicities of grade 2 or higher, excluding alopecia, caused by any prior treatment.
8. Individuals with multiple factors that affect oral medication administration, such as dysphagia, chronic diarrhea, and intestinal obstruction.
9. Individuals with urine routine showing urinary protein ≥++, and confirmed 24-hour urine protein quantification \>1.0 g.
10. Individuals who underwent major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to randomization.
11. Abnormal coagulation function: INR \>1.5 or prothrombin time (PT) \> ULN + 4 seconds or APTT \> 1.5 ULN, with a bleeding tendency or receiving thrombolytic or anticoagulation therapy. Patients who experienced any bleeding or hemorrhagic events ≥ grade 3 CTCAE within 4 weeks prior to randomization, with unhealed wounds, ulcers, or fractures.
12. Occurrence of arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism.
13. Pregnant or lactating women.
14. Presence of distant metastasis.
15. Patients with significant bone marrow suppression.
16. Patients with mental illness or a history of substance abuse with psychotropic drugs.
17. Patients who participated in other drug clinical trials within 4 weeks.
18. Patients with accompanying diseases that, in the investigator's judgment, pose a serious risk to patient safety or may affect the patient's completion of the study.
19. Patients with inherited bleeding tendencies, coagulation disorders, potential invasion of major blood vessels, and other bleeding risks, who experienced clinically significant bleeding symptoms or had a clear bleeding tendency with gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood ++ and above within 3 months prior to enrollment.
20. Patients deemed unsuitable
