Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients

Inclusion Criteria:

• Age ≥18 and ≤75 years old
• Histologically confirmed colorectal adenocarcinoma
• Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
• Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, andpMMR/MSS
• Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
• Primary colorectal tumor has been or can be radically resected
• Liver metastatic lesions are resectable (including radiofrequency ablation and SBRT),and postoperative NED (no evidence of disease) is expected. Resectable livermetastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection can beperformed (including radiofrequency ablation and SBRT); ③ Sufficient residual livervolume is expected after resection; ④ At least one hepatic vein can be preserved afterresection, with preserved blood flow in and out of the residual liver and preservedbile ducts, and can preserve at least two adjacent liver segments; ⑤ No extrahepaticmetastases.
• No prior anti-tumor therapy for liver metastases, except for surgical resection ofprimary lesions
• Normal hematological function (platelets >90×109/L; white blood cells >3×109/L;neutrophils >1.5×109/L)
• Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 timesULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin ≥35g/L
• Liver function classified as Child-Pugh grade A
• Serum creatinine below the upper limit of normal (ULN), or calculated creatinineclearance rate >50ml/min (using Cockcroft-Gault formula)
• ECOG performance status 0-1
• Expected lifespan >3 months
• Signed written informed consent
• Willing and able to be followed up until death or end of study or study termination.

Exclusion Criteria:

• Diagnosis of colorectal cancer with distant extrahepatic metastases
• Prior chemotherapy, targeted therapy, intervention, or immunotherapy for livermetastases
• No planned surgical resection for liver metastatic lesions
• Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one year
• Any toxicity residuals from previous chemotherapy, excluding alopecia, such asperipheral neuropathy ≥NCI CTC v3.0 grade 2
• Use of immunosuppressive drugs one week prior to study treatment initiation, excludingtopical corticosteroids via nasal, inhalational, or other routes or physiologicaldoses of systemic corticosteroids (i.e., not exceeding 10 mg/day of prednisone orequivalent) or steroids used for prevention of contrast agent allergy
• Interstitial lung disease requiring corticosteroid treatment
• Known active autoimmune disease requiring symptomatic treatment or with a history ofsuch disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia, orGraves' disease who have not required systemic treatment within the past 2 years,patients with hypothyroidism requiring only thyroid hormone replacement therapy, andpatients with type I diabetes requiring only insulin replacement therapy can beincluded
• Known history of primary immunodeficiency
• Patients with active tuberculosis
• History of allogeneic organ or hematopoietic stem cell transplantation
• Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil,oxaliplatin) preparation or excipient component
• Bleeding tendency or coagulation disorder
• Significant symptoms of intestinal obstruction
• Hypertensive crisis or hypertensive encephalopathy
• Severe uncontrolled systemic complications such as infection or diabetes
• Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6months before enrollment), myocardial infarction (within 6 months before enrollment),hypertension that remains uncontrolled after appropriate drug treatment, unstableangina pectoris, congestive heart failure (NYHA 2-4), or arrhythmia requiringmedication
• Past or physical examination showing central nervous system diseases (such as primarybrain tumor, epilepsy uncontrolled by standard treatment, any history of brainmetastasis, or stroke)
• Diagnosis of other malignant tumors within the past 5 years (excluding basal cellcarcinoma and/or carcinoma in situ of the cervix after radical surgery)
• Patients who received any investigational drug therapy within the last 28 days priorto the study
• Pregnant or lactating women and women of childbearing age not using or refusing to useeffective non-hormonal contraception (intrauterine devices, barrier contraceptioncombined with spermicidal gel, or sterilization surgery) or men with reproductivepotential unwilling or unable to comply with the study protocol