ctDNA-MRD Monitoring After Neoadjuvant Therapy in Gastric Cancer With pCR or MPR

A Prospective, Single-Center Observational Study Evaluating Recurrence Risk Using ctDNA-Based Molecular Residual Disease Monitoring in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma Achieving Pathological Complete Response or Major Pathological Response After Neoadjuvant Therapy

This prospective observational study will enroll adults with gastric or gastroesophageal junction adenocarcinoma who achieve pathological complete response or major pathological response after neoadjuvant therapy and R0 gastrectomy. The study will evaluate whether postoperative circulating tumor DNA-based molecular residual disease status can identify participants at increased risk of recurrence despite a favorable pathological response. All postoperative treatment decisions will be made by the treating clinicians according to routine care and will not be assigned by the study. Tumor-informed ctDNA-MRD testing will be performed longitudinally, and results will not be used to alter treatment. Participants will be followed for disease-free survival, overall survival, recurrence detection, and adverse events.

This is a prospective, single-center, noninterventional real-world cohort study in participants with locally advanced gastric or gastroesophageal junction adenocarcinoma who have completed neoadjuvant therapy, undergone R0 gastrectomy, and achieved pathological complete response or major pathological response.

The primary objective is to assess the prognostic stratification value of postoperative ctDNA-based molecular residual disease status. Secondary objectives are to compare disease-free survival across clinician-selected postoperative adjuvant treatment strategies among ctDNA-MRD-negative participants, evaluate the diagnostic performance and lead time of ctDNA-MRD monitoring for recurrence, and describe adverse events associated with routine postoperative treatment.

The tumor-informed ctDNA-MRD assay will use somatic variants identified from diagnostic biopsy or resection tissue to construct an individualized monitoring panel. Plasma cell-free DNA will undergo ultra-deep sequencing with molecular error correction. A negative result is defined as no stable detection of tumor-derived variants at an allele frequency of 0.02 percent or higher in a quality-controlled sample with adequate cell-free DNA input. Blood is planned before surgery, approximately 1 month after surgery before adjuvant treatment, approximately 3 months after surgery or after completion of adjuvant chemotherapy, and subsequently every 3 to 6 months when feasible. ctDNA-MRD results are intended for correlative analysis and will not direct changes in clinical treatment.

Postoperative adjuvant therapy will be selected by treating clinicians according to applicable guidelines, pathological and molecular features, treatment tolerance, multidisciplinary discussion, participant preference, and financial considerations. The study will not randomize participants or assign therapy. Imaging and survival follow-up will occur every 3 months during the first postoperative year and every 3 to 6 months thereafter through 3 years after surgery or until recurrence or death. Analyses will include Kaplan-Meier estimates, Cox proportional hazards models, and propensity score methods to address measured confounding in comparisons of treatment strategies.

Inclusion Criteria:

• Age 18 to 75 years.
• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma.
• Completion of preoperative neoadjuvant therapy followed by R0 gastrectomy.
• Postoperative pathological complete response, defined as Becker tumor regression grade 1a or Ryan tumor regression grade 0, or major pathological response, defined as Becker tumor regression grade 1b or Ryan tumor regression grade 1 with 10 percent or less residual viable tumor.
• Willingness to undergo serial blood collection and follow-up and provision of written informed consent.
• Eastern Cooperative Oncology Group performance status of 0 or 1 with adequate major organ function.
• Adequate diagnostic biopsy or preoperative tumor tissue for 1021-gene panel testing.

Exclusion Criteria:

• Postoperative pathological assessment showing neither pathological complete response nor major pathological response, including more than 10 percent residual viable tumor or Becker tumor regression grade 2 to 3.
• Distant metastatic disease identified intraoperatively or postoperatively.
• Another malignant tumor within the previous 5 years.
• Severe postoperative complications preventing any postoperative antitumor therapy.
• Contraindication to immunotherapy, including active autoimmune disease.