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 car…