Modified Short-Course Radiotherapy Combined With Tislelizumab and CAPOX for pMMR/MSS Rectal Cancer

Prior treatment

• 1\. Prior use of PD-1, PD-L1 or other immune checkpoint inhibitors.
• 2\. Prior receipt of any anti-tumor therapy for colorectal cancer, including radiotherapy, chemotherapy, or tumor resection.
• 5\. Participation in another anti-tumor investigational drug clinical trial within 4 weeks prior to enrollment.
• 7\. Confirmed immunodeficiency disease or active autoimmune disease, including but not limited to systemic lupus erythematosus, inflammatory bowel disease, myasthenia gravis, autoimmune hepatitis, rheumatoid arthritis, multiple sclerosis, glomerulonephritis, vasculitis, etc.; use of other immunosuppressants or systemic corticosteroids for immunosuppressive purposes within 4 weeks prior to enrollment.
• 11\. Severe infection (CTCAE grade \>2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; active pulmonary inflammation indicated on baseline chest imaging; active tuberculosis infection identified by medical history or CT scan, history of active tuberculosis within 1 year before enrollment, or history of active tuberculosis \>1 year previously without adequate treatment.

Other illness

• 6\. History of hypersensitivity to any components of monoclonal antibodies, tislelizumab, capecitabine, or oxaliplatin.
• 8\. Known human immunodeficiency virus (HIV) infection; known clinically significant liver disease, including viral hepatitis \[active HBV infection (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL), hepatitis C (positive anti-HCV antibody with HCV RNA above the assay lower limit of detection)\].
• 10\. Uncontrolled cardiac clinical signs or diseases, including but not limited to: a) NYHA class II or higher heart failure; b) unstable angina; c) myocardial infarction within the past 1 year; d) clinically significant supra-ventricular or ventricular arrhythmia that is untreated or poorly controlled after clinical intervention.
• 12\. Diagnosis of another malignancy within 5 years before the first dose of study drug, except for malignancies with low risk of metastasis or death (5-year survival rate \>90%), such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• 14\. Vulnerable populations other than the elderly or illiterate subjects, including patients with psychiatric disorders, cognitive impairment, critically ill patients, etc.
• 15\. Other conditions that, in the investigator's judgment, may force premature termination of study participation.

Lab values

• 9\. Diseases associated with high bleeding risk such as gastrointestinal hemorrhage, bleeding diathesis, or thromboembolic diseases requiring long-term oral anticoagulants or anti-platelet agents.

Other

• 3\. Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR).
• 4\. Presence of peritoneal metastasis or metastasis to other distant organs.
• 13\. Pregnant or lactating women.

• 1\. Participants aged 18 years or older, regardless of gender.
• 2\. Tumor located in the rectum, ≤10 cm from the anal verge.
• 3\. Histologically confirmed adenocarcinoma, with pMMR by immunohistochemistry or MSS by genetic testing.
• 4\. Clinical stage cT3-4N0/+M0.
• 5\. ECOG PS 0-1.
• 6\. Adequate function of major organs and bone marrow.
• 7\. No contraindications to surgery.
• 8\. Good compliance and willingness to complete subsequent follow-up.
• 9\. Voluntary participation in this study and signed informed consent form.