Research on Colorectal Cancer Recurrence Monitoring and Individualized Treatment Based on MRD

Research on Colorectal Cancer Recurrence Monitoring and Individualized Treatment Based on MRD

This study aims to evaluate whether plasma molecular residual disease (MRD), assessed using circulating tumor DNA (ctDNA), can help optimize the duration of immunotherapy in patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

Patients with MSI-H/dMMR metastatic colorectal cancer can achieve durable responses to immune checkpoint inhibitors, but the optimal duration of treatment remains uncertain. Prolonged immunotherapy may increase treatment burden and the risk of immune-related adverse events. ctDNA-based MRD testing may provide a sensitive method for detecting residual tumor burden and identifying patients who may be able to safely stop treatment.

In this study, patients receiving immunotherapy will undergo serial plasma MRD testing. After completing 1 year of immunotherapy, patients with two consecutive negative MRD results will be randomly assigned to either continue immunotherapy or stop treatment and enter observation. Patients will then be followed every 3 months for 2 years with MRD testing and routine clinical assessments, including imaging and laboratory examinations.

The study will compare clinical outcomes between the two groups and evaluate whether serial plasma MRD monitoring can support a more individualized approach to the duration of immunotherapy in MSI-H/dMMR metastatic colorectal cancer.

Inclusion Criteria:

1. Voluntary participation in the study and provision of written informed consent.
2. Age ≥18 years at the time of signing informed consent.
3. Histologically confirmed colorectal adenocarcinoma with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status.
4. Clinically confirmed stage IV disease.
5. No prior immunotherapy for the current colorectal cancer.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Availability of adequate pretreatment tumor tissue and peripheral blood samples for whole-exome sequencing (WES) and personalized circulating tumor DNA (ctDNA)/MRD analysis.
8. Life expectancy >12 months.
9. Willing and able to comply with the study procedures and scheduled follow-up.

Exclusion Criteria:

1. Presence of another malignancy.
2. Prior immunotherapy for the current stage IV colorectal cancer.
3. Organ transplantation within 3 months before enrollment.
4. History of blood transfusion within 3 months before enrollment.
5. Active, known, or suspected autoimmune disease, or evidence of active or chronic infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).
6. Pregnancy or breastfeeding.
7. Presence of a serious concurrent disease that, in the investigator's judgment, may substantially affect life expectancy or study participation.
8. Failure to provide written informed consent.
9. Any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.