Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)

Inclusion Criteria: * • Voluntarily signs a written informed consent form. * Aged between 18 and 75 years at the time of enrollment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Expected survival of more than 2 years. * Histologically confirmed rectal adenocarcinoma. * Tumor biopsy indicates proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2, or molecular testing confirms microsatellite stability (MSS). * Clinical stage T3-4N0M0 or TanyN+M0 based on the 8th edition of the AJCC TNM classification, as evaluated by high-resolution MRI ± endoscopic ultrasound/transrectal ultrasonography, with the tumor located in the mid-to-lower rectum below the peritoneal reflection. * Prior to enrollment, a qualified surgical attending physician must assess the patient's medical history and confirm eligibility for curative R0 resection. * No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy. * Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes. * Adequate organ function, defined as follows: * Hematologic (without use of blood components or growth factors within 7 days prior to treatment initiation): * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L * Platelet count ≥ 100 × 10⁹/L * Hemoglobin ≥ 90 g/L * Renal: * Calculated creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula: CrCl (mL/min) = \[(140 - age) × weight (kg) × 0.85 (if female)\] / (72 × serum creatinine \[mg/dL\]) * Urine protein \< 2+ on dipstick or \< 1.0 g per 24-hour collection * Hepatic: * Total bilirubin ≤ 1.5 × ULN * AST and ALT ≤ 2.5 × ULN * Serum albumin ≥ 28 g/L * Coagulation: * INR and APTT ≤ 1.5 × ULN * Cardiac: * Left ventricular ejection fraction (LVEF) ≥ 50% * Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to initiating study treatment. If the urine test is inconclusive, a serum test must confirm the negative result. Women of childbearing potential who are sexually active with non-sterilized male partners must agree to use highly effective contraception from screening through 120 days after the last dose of study drug. The need for continued contraception beyond this period should be discussed with the investigator. * Women of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and have not undergone menopause (defined as ≥12 months of amenorrhea without alternative medical cause, with FSH levels in the postmenopausal range). * Highly effective contraception methods are those with \<1% failure rate per year when used consistently and correctly (e.g., hormonal contraceptives). In addition to barrier methods, hormonal contraception is required. Periodic abstinence and the calendar method are not considered acceptable. * Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements. Exclusion Criteria: * • Presence of suspected metastatic lesions or unresectable locally advanced disease, regardless of clinical stage. * History of any other malignancy within 5 years prior to enrollment, excluding those considered cured by local therapy (e.g., basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast). * Lesions initially staged as T1N0 eligible for local excision, or T2N0 suitable for sphincter-preserving surgery after multidisciplinary discussion. * Evidence of acute conditions requiring emergency surgery, such as bowel obstruction, perforation, or gastrointestinal bleeding. * Synchronous multiple primary rectal cancers. * History of pelvic or abdominal radiotherapy. * Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption. * Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell-based therapies), biologics, or small-molecule targeted therapy. * Use of nonspecific immunomodulatory treatments (e.g., interleukins, interferons, thymic peptides, tumor necrosis factor) within 2 weeks prior to study treatment (excluding IL-11 for thrombocytopenia), or use of herbal or traditional Chinese medicines with anti-tumor indications within 1 week prior to treatment. * Active autoimmune disease requiring systemic treatment (e.g., with disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years. Replacement therapies (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments. * History of or current interstitial lung disease or non-infectious pneumonitis requiring systemic corticosteroid treatment. * History of bleeding disorders or coagulopathy; patients requiring long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2). * Uncontrolled comorbidities, including but not limited to: decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe peptic ulcer or gastritis, or psychiatric/social conditions affecting compliance or consent. * History of myocarditis, cardiomyopathy, or malignant arrhythmias; unstable angina, heart failure requiring hospitalization, or vascular disease (e.g., aortic aneurysm requiring repair or deep vein thrombosis) within 12 months prior to study treatment; other cardiac conditions impacting safety (e.g., poorly controlled arrhythmia, myocardial infarction, or ischemia). * Within 6 months prior to treatment: history of gastroesophageal varices, severe ulcers, non-healed wounds, gastrointestinal perforation, fistulas, bowel obstruction, intra-abdominal abscess, or acute GI bleeding. * Arterial thromboembolism, grade ≥3 venous thromboembolism (per NCI-CTCAE v5.0), transient ischemic attack, stroke, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to study treatment. * Acute exacerbation of COPD within 1 month prior to treatment; current hypertension not controlled to \<160/100 mmHg despite antihypertensive medication. * Active or prior inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea. * Severe infections within 4 weeks prior to treatment, including complications requiring hospitalization, sepsis, or severe pneumonia; active infections requiring systemic anti-infective therapy within 10 days prior to treatment (excluding antiviral therapy for HBV or HCV). * Major surgery or serious trauma within 30 days prior to treatment; minor local surgery within 3 days (excluding PICC placement). * History of immunodeficiency or HIV antibody positivity; long-term systemic corticosteroid or immunosuppressive therapy. * Active tuberculosis or suspected TB not ruled out via clinical assessment (e.g., sputum test, chest X-ray); known active syphilis. * History of allogeneic organ or hematopoietic stem cell transplantation. * Untreated active hepatitis B (HBsAg-positive with HBV DNA \> 1,000 copies/mL or 200 IU/mL); active hepatitis C (HCV antibody-positive with detectable HCV RNA). * Receipt of a live vaccine within 30 days prior to treatment or planned live vaccination during the study. * Known hypersensitivity to any component of the investigational drugs, or history of serious hypersensitivity reactions to monoclonal antibodies. * Known history of psychiatric disorders, substance abuse, alcoholism, or drug addiction. * Pregnant or breastfeeding women. * Any disease, treatment, or abnormal laboratory finding that may interfere with study results, affect full study participation, or is not in the patient's best interest. * Systemic or local disease caused by a benign tumor, or tumor-related complications/symptoms that pose high medical risk or survival uncertainty (e.g., leukemoid reaction with WBC \> 20 × 10⁹/L, cachexia with \>10% weight loss in 3 months prior to screening, or BMI ≤18).