Short-Course Radiotherapy Followed by Sequential Chemotherapy Combined With PD-1 Monoclonal Antibody and Bevacizumab Versus Short-Course Radiotherapy Followed by Sequential Chemotherapy as Total Neoadjuvant Therapy in pMMR/MSS Locally Advanced Rectal Cancer
Safety and efficacy of 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. Complete Response (CR) Rate of 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.
• Voluntarily signed written informed consent form.
• Age ≥18 and ≤75 years at enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy \>2 years.
• Histologically confirmed rectal adenocarcinoma.
• Tumor biopsy demonstrating pMMR (all four mismatch repair proteins-MSH1, MSH2, MSH6, and PMS2-positive by immunohistochemistry) or genetic testing confirming MSS (microsatellite stable).
• 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.
• Pre-enrollment surgical evaluation by an attending surgeon confirming eligibility for curative-intent R0 resection.
• No prior systemic or local anti-cancer therapy for rectal cancer (radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy).
⁃ Willingness to provide tumor tissue (archival or fresh biopsy) and peripheral blood samples for biomarker analysis during screening and study procedures.
⁃ Adequate organ function.
⁃ 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.
⁃ The subject is willing and able to comply with scheduled visits, treatment regimens, laboratory tests, and other study requirements as outlined in the protocol.