This prospective observational study (PKU-ESCC-Monitor) aims to characterize the dynamic evolution of esophageal squamous cell carcinoma (ESCC) using integrated multi-omics, including tissue genomics, ctDNA, imaging features, immune profiling and microbiome. Two cohorts will be followed: a peri-operative cohort after standard neoadjuvant therapy and surgery, and an advanced cohort receiving first-line immunotherapy. Clinical outcomes (DFS/PFS/OS) and biomarker dynamics will be analyzed to improve risk stratification and response prediction.

The study integrates clinical data with multi-omics (tumor tissue, surgical specimens, archived FFPE slides where applicable, serial blood for ctDNA and cytokines such as IL-6/IL-8, and exploratory immune/microbiome assessments). Patients are followed monthly or per routine visits up to 36-60 months. Analyses include RECIST 1.1-based responses (ORR, DCR, TTR, DOR), survival endpoints, and biomarker-clinical modeling to delineate ESCC evolutionary patterns and treatment response.

Inclusion Criteria:

Peri-operative cohort:

1. Age ≥18 and <80 years; ECOG 0-1.
2. Histologically confirmed ESCC.
3. Completed standard neoadjuvant therapy and planned/underwent 4.transthoracic esophagectomy with routine surgical specimens available.

5.Able to provide clinical course/outcomes and comply with follow-up at participating sites.

Advanced first-line immunotherapy cohort:

1. Age ≥18 and <80 years; ECOG 0-1.
2. Histologically confirmed ESCC, or highly suspected by endoscopy/imaging when surgery is not feasible.
3. No prior systemic anti-cancer therapy for advanced disease; archived FFPE slides (3-5 µm, 5-8 slides) acceptable if fresh tissue unavailable.
4. Able to provide clinical information and comply with follow-up.

Exclusion Criteria:

1. Prior anti-cancer therapy (except standard neoadjuvant therapy in the peri-operative cohort).
2. Other malignancy within 5 years (exceptions: non-melanoma skin cancer, in-situ melanoma, in-situ cervical cancer).
3. Inadequate clinical information.
4. Known infection with HIV, HBV, HCV, or syphilis.
5. Pre-operative imaging indicates insufficient tumor tissue (no visible target region) for study procedures.
6. Any condition deemed by investigators to make the patient unsuitable.

Adults (18-79 years) with histologically confirmed esophageal squamous cell carcinoma (ESCC) treated at Peking University Cancer Hospital and participating centers in China. Two prospective cohorts: (1) peri-operative patients who complete standard neoadjuvant therapy and undergo transthoracic esophagectomy; (2) unresectable/advanced ESCC receiving standard-of-care first-line immunotherapy. ECOG 0-1. Tumor tissue (biopsy or surgical; archived FFPE slides acceptable if fresh tissue is unavailable) and serial blood are collected for multi-omics analyses. Key exclusions include prior systemic therapy for advanced disease (except neoadjuvant in the peri-operative cohort), other active malignancies within 5 years (allowing non-melanoma skin and in-situ cervical cancer), inadequate clinical information, or investigator-assessed unsuitability.