Neoadjuvant Moderately Hypofractionated Radiotherapy Combined With Chemotherapy and Immunotherapy for High-risk pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Multi-center Randomized Control Phase II Trial

Inclusion Criteria:

* Age ≥ 18 years and ≤ 75 years.
* Histologically confirmed colorectal adenocarcinoma with the lower margin of the lesion ≤ 10 cm from the anal verge as assessed by MRI, and immunohistochemistry confirming pMMR, or genetic testing demonstrating MSI-L or MSS.
* Presence of at least one of the following high-risk factors as assessed by pelvic MRI: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph node (longest diameter \> 7 mm).
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
* No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
* Able to tolerate radiotherapy, chemotherapy, and immunotherapy: ECOG performance status score 0-2. Laboratory results: white blood cell count ≥ 4.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 80 g/L, ALT \< 2 × ULN, total bilirubin \< 35 μmol/L, serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min, thyroid-stimulating hormone within normal range (patients with stable thyroid function after hormone replacement therapy may be enrolled).
* Willing to participate and able to provide written informed consent.

Exclusion Criteria:

* Presence of distant metastasis.
* Patients with stage I or II rectal cancer who do not require preoperative neoadjuvant therapy.
* Severe diseases involving the heart, lung, brain, kidney, gastrointestinal tract, or other systemic conditions.
* Untreated chronic hepatitis B or HBV carriers with HBV DNA \> 500 IU/mL, or patients positive for HCV RNA. Patients with inactive hepatitis B surface antigen (HBsAg) carriers, those with hepatitis B who have been treated and are stable (HBV DNA \< 500 IU/mL), and those who have been cured of hepatitis C may be enrolled.
* Active autoimmune disease or history of autoimmune disease with potential for relapse.
* Receipt of corticosteroids (at a dose equivalent to prednisone \> 10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
* History of thyroid dysfunction.
* Severe chronic or active infection requiring systemic antifungal or antiviral therapy, including tuberculosis infection.
* History of allergic constitution or allergy to multiple drugs.
* History of prior pelvic radiotherapy.
* History of inflammatory bowel disease.
* Unwillingness to participate or inability to provide written informed consent.