A Clinical Trial Comparing Long-Course Versus Short-Course Radiotherapy Followed by Immunotherapy Combined With Total Neoadjuvant Therapy (TNT) to Long-Course Radiotherapy Followed by TNT in High-Risk Locally Advanced Rectal Cancer

Inclusion Criteria: 1. Patients or their family members agree to participate in the study and sign the informed consent form; 2. Age 18-75 years, male or female; 3. Histologically confirmed Locally Advanced rectal adenocarcinoma; 4. Immunohistochemistry and/or genetic testing confirmed pMMR/MSS; 5. inferior margin ≤ 10 cm from the anal verge; 6. Pelvic MRI shows high risk \[meets one of the following conditions\]: • Clinical tumor (cT) staging cT4a or cT4b (according to AJCC 8th Edition) • Extramural vascular infiltration • Clinical lymph node (cN) staging cN2 (according to AJCC 8th Edition) • Mesenteric fascia is involved • Lateral lymph node enlargement 7. ECOG performance status score is 0-1; 8. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc; 9. There was no operative contraindication; 10. Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 11. Urinary protein \< 2+ or 24-hour urinary protein excretion \< 1 g at baseline. Exclusion Criteria: 1. Patients with non-high-risk pMMR LARC； 2. Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms; 3. Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).