Short-Course Radiotherapy Followed by Immunotherapy Combined With Chemotherapy for Microsatellite Stable Locally Advanced Rectal Cancer: A Prospective, Randomized, Controlled Phase II Clinical Trial

Inclusion criteria

• Age 18-75 years, regardless of gender;
• Stage II/III disease (cT3-T4N0 or cT2-4N+) without distant metastasis on magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS), according to the 8th edition of the AJCC Cancer Staging Manual (2018);
• The lower boundary of the lesion is ≤ 10 cm from the anal verge, confirmed by colonoscopy or digital rectal examination;
• Pathologically confirmed or re-reviewed rectal adenocarcinoma;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Meet the following laboratory diagnostic indicators:

Hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.5×10⁹/L;

• Neutrophil count ≥ 1.5×10⁹/L, platelet count ≥ 100×10⁹/L;
• Creatinine ≤ 1.0×upper normal limit (UNL), blood urea nitrogen (BUN) ≤ 1.0×UNL;
• Alanine aminotransferase (ALT) ≤ 1.5×UNL;
• Aspartate aminotransferase (AST) ≤ 1.5×UNL;
• Alkaline phosphatase (ALP) ≤ 1.5×UNL;
• Total bilirubin (TBIL) ≤ 1.5×UNL;
• Urinary protein (-); normal bleeding and coagulation time.
• No history of allergy to platinum-based drugs;
• For patients with primary rectal cancer, no surgery (except palliative colostomy), chemotherapy, or other anti-tumor treatments have been performed from diagnosis to enrollment;
• No previous radiation therapy to the intended radiation field;
• Signed informed consent form.

Exclusion criteria

• Previous treatment with anti-PD-1/L1, anti-CTLA-4 immunotherapeutic drugs, or other experimental immunotherapeutic agents;
• Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.;
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia;
• Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation;
• History of other malignant tumors, excluding curable non-melanoma skin cancer and carcinoma in situ of the cervix;
• Patients with active infection, heart failure, myocardial infarction within 6 months, unstable angina pectoris, or unstable arrhythmia;
• Physical examination or clinical laboratory findings that the investigator believes may interfere with the results or increase the risk of treatment complications in patients, or other uncontrollable diseases;
• Lactating or pregnant women;
• Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or history of organ transplantation or allogeneic stem cell transplantation;
• Known active hepatitis B virus (HBV) infection (HBV-DNA ≥ 2000 U/mL), hepatitis C virus (HCV) infection, or active pulmonary tuberculosis infection;
• Patients who have received tumor vaccines or other vaccines within 4 weeks before the start of treatment; (Note: Seasonal influenza vaccines for injection are mostly inactivated vaccines and thus allowed, while intranasal preparations are usually live attenuated vaccines and thus not allowed);
• Patients receiving concurrent use of other immunomodulators, chemotherapeutic drugs, drugs in other clinical studies, or long-term cortisol therapy are not eligible for enrollment;
• Patients with mental illness, substance abuse, or social problems that affect compliance will not be enrolled after review by doctors;
• Patients with allergies or contraindications to the study drugs.