Short-course Radiotherapy Followed by Sequential Chemotherapy With or Without PD-1 Monoclonal Antibody and Bevacizumab as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer （SPARK）

Inclusion Criteria:

1. Voluntarily signed written informed consent form.
2. Age ≥18 and ≤75 years at enrollment.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
4. Life expectancy \>2 years.
5. Histologically confirmed rectal adenocarcinoma.
6. Tumor biopsy demonstrating pMMR (all four mismatch repair proteins-MSH1, MSH2, MSH6, and PMS2-positive by immunohistochemistry) or genetic testing confirming MSS (microsatellite stable).
7. Clinical stage II-III rectal cancer (cT3-4NanyM0 or cTxN+M0) per AJCC 8th Edition TNM staging, assessed via high-resolution MRI ± endoscopic ultrasound/transrectal Doppler ultrasound. Tumor must be ≤12 cm from the anal verge by MRI.
8. Pre-enrollment surgical evaluation by an attending surgeon confirming eligibility for curative-intent R0 resection.
9. No prior systemic or local anti-cancer therapy for rectal cancer (radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy).
10. Willingness to provide tumor tissue (archival or fresh biopsy) and peripheral blood samples for biomarker analysis during screening and study procedures.
11. Adequate organ function.
12. For women of childbearing potential (WOCBP):Negative urine or serum pregnancy test within 3 days prior to treatment (serum test required if urine result is inconclusive).Agreement to use highly effective contraception (e.g., intrauterine device, hormonal implants) from screening until 120 days after last study treatment. Periodic abstinence and calendar-based methods are prohibited.
13. The subject is willing and able to comply with scheduled visits, treatment regimens, laboratory tests, and other study requirements as outlined in the protocol.

Exclusion Criteria:

1. Suspected metastatic lesions or locally advanced unresectable disease regardless of stage.
2. History of other malignancies within 5 years prior to enrollment, except those cured by local therapy (e.g., basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the breast).
3. Concurrent participation in another interventional clinical trial (observational or non-interventional studies allowed).
4. Acute complications requiring emergency surgery (e.g., bowel obstruction, perforation, hemorrhage).
5. Multiple primary rectal cancers.
6. Prior pelvic/abdominal radiotherapy.
7. Conditions impairing oral drug absorption (e.g., dysphagia, malabsorption syndrome).
8. Prior systemic/local anti-tumor therapy for locally advanced rectal cancer (surgery, chemotherapy, radiotherapy, immunotherapy \[checkpoint inhibitors/agonists, cell therapy\], biologics, or targeted agents).
9. Non-specific immunomodulators (e.g., interleukins, interferons) within 2 weeks or anti-tumor herbal medicines within 1 week prior to treatment.
10. Active autoimmune disease requiring systemic immunosuppression (e.g., corticosteroids \>10 mg/day prednisone equivalent) within 2 years (hormone replacement allowed).
11. History of non-infectious pneumonitis or interstitial lung disease requiring steroids.
12. Bleeding diathesis/coagulopathy or chronic anticoagulation (e.g., CHADS2 score ≥2 for atrial fibrillation).
13. Uncontrolled comorbidities (e.g., decompensated cirrhosis, nephrotic syndrome, peptic ulcers) or psychiatric disorders affecting consent/study compliance.
14. Cardiac history:Myocarditis/cardiomyopathy/malignant arrhythmias.Unstable angina/CHF within 12 months.Arterial thromboembolism within 6 months (e.g., stroke, TIA).Grade ≥3 venous thromboembolism (CTCAE v5.0).Uncontrolled hypertension (SBP ≥160 mmHg/DBP ≥100 mmHg).
15. Active inflammatory bowel disease (Crohn's/ulcerative colitis) or chronic diarrhea.

16Active severe infection requiring hospitalization/systemic antibiotics within 4 weeks (excluding HBV/HCV antivirals).

17.Major surgery/trauma within 30 days or minor procedures within 3 days (excluding PICC placement).

18.Immunodeficiency (HIV-positive, chronic immunosuppressants). 19.Active tuberculosis (confirmed by sputum/X-ray) or syphilis. 20.Prior allogeneic organ/stem cell transplantation. 21.Active hepatitis:HBV: HBsAg+ with HBV-DNA \>1000 copies/mL (200 IU/mL) without antiviral therapy.HCV: Anti-HCV+ with detectable HCV-RNA.

22.Live vaccines within 30 days or planned during study. 23.Hypersensitivity to study drugs/monoclonal antibodies. 24.Substance abuse or psychiatric disorders compromising compliance. 25.Pregnancy/lactation. 26.Conditions confounding efficacy/safety assessments or limiting survival evaluation (e.g., leukemoid reaction \[WBC \>20×10⁹/L\], cachexia \[\>10% weight loss in 3 months\], BMI ≤18).

27.Other conditions deemed inappropriate by investigators.