PD-1 + FOLFOXIRI vs CAPOX as Total Neoadjuvant Therapy for pMMR Low Rectal Cancer

Inclusion Criteria:

* Histologically confirmed rectal adenocarcinoma.
* pMMR status documented by immunohistochemistry (MSH1, MSH2, MSH6 and PMS2 all positive) or by MSI testing showing MSS or MSI-L.
* Primary tumor located within 5 cm from the anal verge on pelvic MRI.
* Clinical stage cT3-4bN0M0 or cTxN+M0, with or without positive mesorectal fascia (MRF) and/or extramural vascular invasion (EMVI), and assessed by the multidisciplinary team as resectable with the potential for R0 resection.
* No clinical or radiologic evidence of bowel obstruction.
* No prior colorectal surgery.
* No prior chemotherapy or radiotherapy.
* No prior treatment with biologic agents (e.g., monoclonal antibodies), immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4), or other investigational drugs.
* Age 18 to 75 years (inclusive).
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Estimated life expectancy \> 2 years.
* Adequate bone marrow function: WBC \> 3.5 × 10\^9/L; platelets \> 100 × 10\^9/L; hemoglobin \> 80 g/L.
* Adequate liver function: ALT and AST ≤ 1.5 × upper limit of normal (ULN); total bilirubin \< 23.0 μmol/L.
* Adequate renal function: eGFR ≥ 60 mL/min/1.73 m² (CKD-EPI) or creatinine clearance (Ccr) ≥ 60 mL/min.
* Ability to understand and willingness to sign a written informed consent form.

Exclusion Criteria:

* Evidence of inguinal or lateral pelvic lymph node metastasis (lymph node short-axis diameter ≥ 7 mm or MRI features typical for metastatic lymph nodes).
* Clinically significant cardiac disease, including arrhythmias requiring anti-arrhythmic treatment (except β-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure \> NYHA class II.
* Uncontrolled severe hypertension.
* History of HIV infection or active chronic hepatitis B (HBV DNA \> 2 × 10\^3 IU/mL) or hepatitis C (HCV RNA \> 1 × 10\^3 IU/mL).
* Active pulmonary tuberculosis under treatment or having received anti-tuberculosis therapy within 1 year before screening.
* Other active severe infections (as defined by NCI-CTCAE v5.0).
* Evidence of distant metastasis outside the pelvis before treatment.
* Cachexia or decompensated organ dysfunction.
* Prior pelvic or abdominal radiotherapy.
* Multiple primary colorectal cancers.
* History of seizures requiring ongoing treatment (e.g., corticosteroids or anti-epileptic drugs).
* History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or basal cell carcinoma of the skin.
* Drug or alcohol abuse, or any medical, psychological, or social condition that, in the investigator's judgment, could interfere with study participation or the evaluation of study results.
* Any active autoimmune disease or history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, or hypothyroidism).
* Receipt of any prophylactic vaccine against infectious diseases (e.g., influenza, varicella) within 4 weeks before enrollment.
* Requirement for long-term immunosuppressive therapy or systemic/local corticosteroids at immunosuppressive doses (equivalent to \> 10 mg/day of prednisone or other corticosteroids).
* Known or suspected allergy or hypersensitivity to any study drug or to any component of the study treatments.
* Any unstable condition or other circumstance that may, in the opinion of the investigator, compromise patient safety or study compliance.
* Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use adequate contraception during the study.
* Refusal or inability to provide written informed consent.