Total Neoadjuvant Treatment for pMMR Locally Advanced Low Rectal Cancer: Anti-PD-1 Antibody With FOLFOXIRI and Preoperative Radiation Therapy

Inclusion criteria

• The pathological confirmation is rectal adenocarcinoma. Additionally, the tumor biopsy immunohistochemistry indicates pMMR, with all MSH1, MSH2, MSH6, and PMS2 showing positive expression.
• Age: 18 to 75 years old,allgenders
• MRI examination confirms that the lower margin of the tumor is within 5cm from the anal verge.
• Clinical stage cT3-4N0M0 or cTxN+M0, with or without positive MRF, with or without positive EMVI, estimated to be eligible for R0 resection.
• No signs of intestinal obstruction before surgery; or resolution of obstruction after proximal colostomy surgery
• Performance status (ECOG score) ≤ 2
• Hematology: WBC > 3 × 10^9 / L; PLT > 80 × 10^9 / L; Hb > 90 g/L;
• Liver function: ALT and AST ≤ 2.5 × ULN; bilirubin ≤ 1.5 × ULN;
• Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;
• Signed informed consent, willingness to undergo treatment according to this protocol, and good compliance with medication.
• No history of prior surgery, chemotherapy, radiation therapy, or immunotherapy.

Exclusion criteria

• Co-existing with other serious illnesses, including severe electrolyte disorders, bleeding tendencies, etc.
• Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV) infection. b) Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×104 copies/mL or >2000 IU/mL)]. c) Known hepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies/mL), or other hepatitis, liver cirrhosis.
• Women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures.
• Patients with severe brain disorders or mental illnesses (such as depression, mania, obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability to self-report.
• Patients with autoimmune diseases, blood system disorders, and a history of organ transplantation, long-term use of steroids, or immunosuppressive agents
• History of other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
• History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation).
• Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).