This study aims to observe and evaluate the efficacy and safety of moderately hypofractionated radiotherapy combined with chemotherapy and immunotherapy, compared with conventional neoadjuvant chemoradiotherapy, in patients with high-risk locally advanced colorectal cancer.

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.