The study is a multicenter, randomized controlled, phase III clinical study, and the purpose of the study is to explore the complete response rate (CR, Defined as pathological complete response (pCR) + Clinical complete response (cCR) sustained for over one year) of patients with locally advanced rectal cancer(LARC) treated with personalized long-course radiotherapy plus chemotherapy with or without Serplulimab. A total of 184 patients were included in this study.

Patients diagnosed with locally advanced rectal cancer (T3-4/N+) and presenting with combined risk factors, where the lower boundary of the lesion is ≤ 10 cm from the anal margin, will undergo neoadjuvant therapy. The primary endpoint of the study is the complete response rate (CR), defined as the combination of pathological complete response (pCR) and clinical complete response (cCR) sustained for over one year.

Inclusion Criteria:

1. Age: ≥18 years old; sex is not limited.

2. Patients with stage II/III rectal cancer staged under MRI or endoscopic ultrasonography and have at least one risk factor: cT4a and invasion of intestinal lumen for more than 1/2 week (measured by MRI)；cT4b(resectable)；cT3c-d with EMVI+ (upper middle rectum)；cN2；MRF+ (≤2mm)；lower rectal cancer is located on the anterior wall and tumor reaching T3 and occupying the intestinal cavity for more than 1/2 week; lower rectal cancer is mainly located on the lateral posterior wall need invading the intestinal wall (anal sphincter) ≥ 5mm； tumor of lower rectal cancer invades the external anal sphincter or levator ani muscle (stage 4) . [According to the 8th edition of the 2018 AJCC Cancer Staging Manual and the 2008 ESMO Lower Segment Colorectal Cancer Staging Criteria] . The preoperative T stage is referred to endoscopic ultrasonography or rectal MRI. The N stage is referred to abdominal CT. The M stage is referred to abdominal and thoracic CT. If symptoms occur, other appropriate imaging examinations are needed (cranial MRI or ECT) . Patients with contraindications to MRI can be interpreted with caution based on CT and endoluminal ultrasound staging. MDT should review the staging of all patients.

3. The lower edge of lesion is less than 10cm from anal verge according to rigid sigmoidoscopy or rectal digital examination.

4. No distant metastasis after a thorough examination .

5. Pathological diagnosis of rectal adenocarcinoma,and Immunohistochemistry and/or genetic testing for MSS/pMMR;

6. ECOG score: 0-1.

7. Patients with primary rectal cancer who had not received surgery prior to surgery (except for palliative ileostomy or colostomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy.

8. The main organ function is normal, including the following characteristics:

   ①Blood routine examination: HB ≥9g/dL, WBC ≥ 3.5/4.0×109/L，NE≥ 1.5×109/L，PLT≥ 100×109/L

   ②Biochemical examination：Crea and BIL ≤ 1.0 upper normal limit（ULN），ALT and AST≤ 2.5 upper normal limit（ULN）, ALP≤2.5×UNL，Tbil≤1.5×UNL。

9. Not allergic to 5-Fu or Platinum.

10. The site of radiotherapy had not previously received radiation.

11. If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF (Informed Consent Form) is signed until 8 weeks after the last dose of study drug.

12. Participants are volunteered to participate in this study, sign informed consent, good compliance, cooperation with follow-up.

Exclusion Criteria:

1. Patients who have previously received pelvic radiotherapy.
2. Presence of active or progressive infection requiring systemic treatment, such as active tuberculosis, active hepatitis, etc.
3. Presence of systemic diseases that are not stably controlled by the investigator, including diabetes mellitus, hypertension, liver cirrhosis, rheumatic immune diseases, and severe lung diseases.
4. Have had prior or concurrent cancer distinct in primary site or histology (including synchronous colon cancer) , except for curatively treated cervical cancer in situ, Basal cell carcinoma of skin.
5. Has any other disease, metabolic abnormality, physical examination abnormality, or laboratory abnormality that, in the judgment of the investigator, has reason to suspect that the patient has a disease or condition for which the study drug is inappropriate for use, or that would affect the interpretation of the study results, or place the patient in a high-risk condition.
6. Estimated inadequate patient compliance to participate in this clinical study.
7. History of gastrointestinal fistula, perforation, bleeding or severe ulceration or presence of severe gastrointestinal disease that affects the absorption of oral chemotherapy drugs.
8. Patients who have received solid organ transplantation or bone marrow transplantation, or have had active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.