MRD-Guided Surveillance in Resectable Stage IV Metastatic Colorectal Cancer (SURVEILLANCE-II)

This is a multicenter, prospective, observational study designed to evaluate the effectiveness of ctDNA-based MRD monitoring in predicting disease recurrence and survival outcomes in patients with resectable stage IV metastatic colorectal cancer (mCRC). The study will enroll 181 patients who have not previously received chemotherapy, radiotherapy, or targeted therapy.

Key Objectives

Primary Objective:

To explore the correlation between MRD status and recurrence-free survival (RFS) in resectable stage IV mCRC patients.

Secondary Objectives:

To assess the relationship between MRD status and 1-year/2-year event-free survival (1yEFS, 2yEFS).

To evaluate the association between MRD status and 2-year recurrence-free survival (2yRFS).

To assess the impact of MRD status on overall survival (OS).

Exploratory Objective:

To determine the average time by which MRD detection precedes imaging-based detection of disease recurrence.

Study Design

Patients will undergo blood sampling at key time points:

Baseline (pre-treatment) Pre-surgery (0-7 days before surgery) Post-surgery (7±2 days after surgery) Follow-up visits at 1, 3, 6, 9, 12, 18, and 24 months post-surgery MRD status will be assessed using a ctDNA methylation-based PCR test, which provides a rapid, cost-effective alternative to traditional NGS-based methods.

Statistical Analysis Kaplan-Meier survival analysis will be used to estimate RFS, EFS, and OS. Cox proportional hazards models will assess whether MRD status serves as an independent prognostic factor for recurrence.

Multivariate analysis will adjust for clinical variables, including tumor burden and treatment history.

Ethical Considerations The study adheres to the principles of the Declaration of Helsinki and Chinese Good Clinical Practice (GCP) guidelines.

Informed consent will be obtained from all participants, and privacy and confidentiality will be strictly maintained.

Expected Outcomes This study aims to validate the clinical utility of ctDNA-based MRD monitoring in predicting recurrence and survival outcomes for resectable stage IV mCRC patients. If successful, MRD testing may offer a more effective tool for postoperative surveillance and treatment planning, allowing for earlier interventions and improved long-term outcomes.

Inclusion criteria

• Age 18-80 years old, male or female;
• histologically confirmed primary foci of colorectal adenocarcinoma (i.e., adenoepithelial carcinoma, including adenocarcinoma, mucinous adenocarcinoma, imprinted cell carcinoma, and undifferentiated carcinoma; excluding adenosquamous carcinoma); (3) Preoperative stage IV and no surgical resection; (4) Not receiving chemotherapy, radiotherapy, targeted therapy or other anti-tumor therapy;

• Surgical resection of primary/metastatic foci is possible; 6) ECOG score 0-1; 7) Subjects voluntarily enrolled in the study and signed the informed consent, good compliance, and actively cooperate with the regular clinical follow-up clinic back in the hospital.

Exclusion criteria

• Previous other malignant tumors (including non-adenocarcinoma colorectal cancer);
• Pregnant and lactating women;
• Patients with other concurrent illnesses that, in the judgment of the investigator, may interfere with follow-up and short-term survival;
• The subject has other factors that may cause this study to be forced to be terminated halfway, such as other serious illnesses (including psychiatric illnesses) that require comorbid treatment, serious laboratory test abnormalities, accompanied by family or social factors that would affect the safety of the subject, or the collection of data and samples.