Numerous studies have confirmed that ctDNA-MRD detection technology based on peripheral blood can identify minimal residual disease (MRD) following surgery and other curative treatments, indicating a higher risk of recurrence. Multiple exploratory studies in esophageal cancer have demonstrated that patients who are ctDNA-MRD positive after definitive chemoradiotherapy (dCRT) exhibit poorer progression-free survival (PFS) and a higher risk of recurrence. Furthermore, the recent NEXUS-1 translational study confirmed that 66.7% of unresectable patients achieved the goal of conversion surgery after receiving definitive chemoradiotherapy combined with immunotherapy. Notably, patients who were ctDNA-MRD positive after chemoradiotherapy had a significantly worse prognosis. These findings suggest that ctDNA-MRD status after chemoradiotherapy has prognostic stratification value and that consolidative immunotherapy is effective.

Based on these previous discoveries, this study aims to investigate the safety and efficacy of an escalated treatment strategy involving immunotherapy combined with chemotherapy for high-risk populations after definitive chemoradiotherapy for esophageal cancer, guided by personalized MRD detection results.

• Inclusion Criteria

  1. Histologically confirmed locally advanced esophageal squamous cell carcinoma (ESCC), with clinical stage Ⅱ-Ⅳ unresectable disease (including unresectable cases, patients with surgical contraindications, or those who refuse surgery). According to the 8th edition AJCC staging system, the pretreatment clinical stage is defined as: cT1N2-3M0, cT2-4bN0-3M0; M1 disease is limited to non-regional lymph node metastases, excluding distant organ metastases.
  2. No prior systemic therapy administered for the disease, and planned to receive definitive chemoradiotherapy (dCRT).
  3. Having undergone 1021-gene large panel testing on tissue samples.
  4. Aged 18-80 years old.
  5. Expected overall survival ≥ 6 months.
  6. ECOG performance status 0-1.
  7. Normal blood biochemical parameters, with normal liver and kidney function.
  8. Able to understand the study protocol, voluntarily participate in the study, and sign the informed consent form.
  9. Good compliance, able to cooperate with specimen collection at all designated time points and provide relevant clinical data.

• Exclusion Criteria

  1. Have participated in other clinical trials within 3 months prior to enrollment.
  2. Have a history of other malignant tumors within 3 years prior to the diagnosis of esophageal cancer.
  3. Have a history of severe mental illness.
  4. Patients who are unable to understand the study protocol and thus cannot cooperate, or who refuse to sign the informed consent form.
  5. Have contraindications to chemoradiotherapy.
  6. Have a history of autoimmune diseases.