Long-course Chemoradiotherapy or Short-course Radiotherapy Combined With CAPOX, PD-1antibody, and COX-2 Inhibitor for MSS Locally Advanced Rectal Cancer (SERRAC)

• Long-course radiotherapy (Radiation), also known as LCRT: Long-course radiation: 50Gy/25Fx
• Oxaliplatin (Drug): Oxaliplatin: 130mg/m2 d1 q3w
• Capecitabine (Drug): Xeloda
• Celecoxib (Drug): celecoxib 200 mg orally twice a day
• Short-course radiotherapy (Radiation), also known as SCRT: Short-course radiotherapy: 25Gy/5Fx
• Serplulimab (Drug): Serplulimab 300mg, d1, q3w

Primary outcomes

• Complete response (CR) rate [1 month after the surgery or the decision of W&W]: Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy.

Secondary outcomes

• Grade 3-4 adverse effects rate [From date of randomization until 3 months after the completion neoadjuvant therapy]: Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
• 3 year anal preservation rate [From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.]: 3 year anal preservation rate
• 3 year disease free survival rate [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]: Rate of 3 year disease free survival
• 3 year local recurrence free survival rate [From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.]: Rate of 3 year local recurrence free survival
• 3 year overall survival rate [From date of randomization until the date of death from any cause, assessed up to 36 months.]: Rate of 3 year overall survival
• Rate of surgical complications [The surgical complications were assessed within 3 months after the surgery.]: Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Age 18-75 years, gender not limited
2. Pathologically confirmed rectal adenocarcinoma
3. ≤10 cm from the anus
4. Baseline stage T3-4/N+
5. No distant metastasis
6. MSI/MMR status MSS/pMMR
7. Karnofsky performance status score ≥70
8. No prior chemotherapy or other anti-cancer treatment prior to enrollment
9. No prior immunotherapy prior to enrollment
10. Ability to comply with the study protocol
11. Written informed consent

Exclusion Criteria:

1. Pregnancy or breast-feeding women;
2. Known history of other malignancies within 5 years;
3. Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc;
4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
7. Uncontrolled infection which needs systemic therapy;
8. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
9. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. Allergic to any component of the therapy.

• Zhen Zhang, M.D, PH.D, Principal investigator, Fudan University