SERRAC is a prospective, multicentre, randomized phase II trial. 138 LARC (T3-4/N+M0, distance from anal verge ≤10cm) patients will be treated with neoadjuvant therapy and assigned to Group A and Group B (1:1). Group 1 receives LCRT (50Gy/25Fx) followed by 3 cycles of CAPOX.Group 2 receives SCRT (25Gy/5Fx) followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody. The COX2 inhibitor celecoxib 200 mg was started orally twice a day during chemotherapy until the end of neoadjuvant treatment.TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal preservation rate, 3-year DFS rate, etc.

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.