The goal of this randomized, controlled phase III clinical trial is to evaluate whether combining Tislelizumab with standard SOX chemotherapy improves disease-free survival (DFS) compared to chemotherapy alone in patients with stage III gastric or gastroesophageal junction adenocarcinoma who are ctDNA-MRD positive after surgery. The study will enroll 416 patients across multiple centers and will compare outcomes between two groups: patients receiving tislelizumab plus SOX chemotherapy and those receiving standard SOX chemotherapy alone. The primary questions to be addressed are whether the combination therapy improves 1-year DFS rates and whether it demonstrates an acceptable safety profile. Participants will provide tissue and blood samples for ctDNA-MRD testing, undergo postoperative adjuvant therapy (chemotherapy ± immunotherapy), and complete regular follow-up visits to monitor treatment response and safety. The trial will assess key outcomes, including DFS, overall survival (OS), and ctDNA clearance rates, to determine the clinical benefit and safety of tislelizumab in this population.

Inclusion Criteria:

Histological or Cytological Confirmation: Patients must have a confirmed diagnosis of stage III gastric or gastroesophageal junction adenocarcinoma (according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system) based on histological or cytological examination.

Surgical Resection: Patients must have undergone D2 or more extensive lymph node dissection surgery, with available tumor tissue samples. Patients who received neoadjuvant therapy prior to surgery are excluded.

Age: Patients must be between 18 and 75 years of age. General Condition: Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Informed Consent: Patients must be able to understand the study protocol and voluntarily participate in the study, providing written informed consent.

Compliance: Patients must demonstrate good compliance, willingness to adhere to the treatment regimen specified in the study protocol, and ability to provide blood samples at designated time points.

Clinical Data: Patients must have complete imaging and pathological clinical data available.

Life Expectancy: Patients must have an expected survival of more than 3 months. Organ and Marrow Function: Patients must have adequate organ and bone marrow function.

Exclusion Criteria:

Inability to Confirm Diagnosis: Patients who cannot be confirmed as having primary stage III gastric or gastroesophageal junction adenocarcinoma through histological or cytological examination.

Inability to Receive Treatment: Patients who are unable to receive immune checkpoint inhibitors or SOX chemotherapy.

Inability to Comply with Follow-up: Patients who are unable to adhere to the predetermined clinical follow-up schedule.

Inability to Accept Study Protocol: Patients who cannot accept the treatment regimen specified in the study protocol.

Inability to Provide Efficacy Assessment: Patients who cannot undergo or provide designated efficacy assessment methods such as CT scans.

Autoimmune Diseases: Patients with a history of autoimmune diseases. Psychiatric or Substance Abuse Issues: Patients with a history of substance abuse that cannot be discontinued or those with psychiatric disorders, or any severe and/or uncontrolled medical conditions.

Severe Comorbidities: Patients with any severe comorbidities that, in the investigator's judgment, may jeopardize patient safety or completion of the study.

Pregnancy or Breastfeeding: Pregnant or breastfeeding women. Prior Neoadjuvant Therapy: Patients who received neoadjuvant therapy prior to surgery or intraoperative chemotherapy infusion.