This study is a national multicenter, prospective randomized, placebo- controlled Phase III clinical trial designed to investigate the potential therapeutic benefit of immunotherapy combined with total neoadjuvant therapy (TNT) and to compare the efficacy of different radiotherapy modalities followed by immunotherapy.

This study is a national multicenter, prospective randomized, placebo- controlled phase III clinical trial, with the following objectives: 1. For patients with LARC, to determine whether the efficacy of TNT combined with immunotherapy is superior to that of the treatment mode of LCRT followed by TNT; 2. To compare the differences in efficacy and toxicity between long-course radiotherapy and short-course radiotherapy under the mode of TNT combined with immunotherapy.

For precision management of patients with cCR post-neoadjuvant therapy, dynamic MRD monitoring was implemented, including baseline and follow-up testing for patients having tumors ≤5 cm from the anal verge.

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. ECOG performance status score is 0-1;
7. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
8. There was no operative contraindication;
9. 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;
10. Urinary protein < 2+ or 24-hour urinary protein excretion < 1 g at baseline.

Exclusion Criteria:

1. Patients with MSI-H/dMMR 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).