Total Neoadjuvant mFOLFOX6 Plus Suvemcitug and Enlonstobart With Selective Omission of Pelvic Radiotherapy for High-Risk Mid-Rectal Locally Advanced Rectal Cancer

Inclusion Criteria:

1. Age 18 to 75 years, male or female.
2. Histologically confirmed rectal adenocarcinoma.
3. pMMR or MSS status confirmed by genetic testing or immunohistochemistry.
4. Tumor lower margin located 5-12 cm from the anal verge, based on colonoscopy or MRI, consistent with mid-rectal cancer.
5. Pelvic MRI showing high-risk locally advanced rectal cancer, meeting at least one of the following criteria: cT3c/d, defined as tumor extension \>5 mm beyond the muscularis propria; cN2 disease, defined as \>=4 regional metastatic lymph nodes; definite extramural venous invasion positivity.
6. No distant metastasis confirmed by chest and abdominal imaging, including contrast-enhanced CT or MRI.
7. ECOG performance status of 0 or 1.
8. Adequate organ function, including absolute neutrophil count \>=1.5 x 10\^9/L; platelet count \>=100 x 10\^9/L; hemoglobin \>=9 g/dL; ALT and AST \<=2.5 x upper limit of normal; total bilirubin \<=1.5 x upper limit of normal; serum creatinine \<=1.5 x upper limit of normal or creatinine clearance \>=50 mL/min.
9. Not pregnant or breastfeeding. Participants of reproductive potential must agree to use effective contraception during study treatment and for the protocol-specified period after the last dose.
10. Voluntary participation with signed written informed consent.

Exclusion Criteria:

1. Imaging evidence of cT4 disease, mesorectal fascia positivity, or lateral lymph node metastasis.
2. Prior pelvic radiotherapy or prior systemic antitumor treatment for the current disease, including chemotherapy, targeted therapy, or immunotherapy.
3. Special histologic subtypes, including mucinous adenocarcinoma, signet-ring cell carcinoma, undifferentiated carcinoma, or other special histologic types.
4. Known allergy or contraindication to any component of the study drugs, including oxaliplatin, 5-fluorouracil, suvemcitug, or enlonstobart.
5. Active or previous severe autoimmune disease, including systemic lupus erythematosus or inflammatory bowel disease, or long-term use of systemic immunosuppressive agents.
6. Serious cardiovascular events within 6 months, including acute myocardial infarction or stroke, refractory hypertension, or NYHA class III-IV heart failure.
7. Active infection, including active tuberculosis, uncontrolled hepatitis B or C, or HIV infection with high viral load.
8. Other malignancy within 5 years, except cured localized skin cancer or carcinoma in situ.
9. Pregnancy or breastfeeding.
10. Inability to undergo MRI examination.
11. Multiple primary colorectal cancers.
12. Intestinal obstruction, intestinal perforation, or high risk of obstruction or perforation.
13. Hypertension that cannot be controlled to the normal range with antihypertensive therapy, defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg.
14. NYHA class III-IV cardiac insufficiency or left ventricular ejection fraction \<50% on echocardiography.
15. Proteinuria, defined as urine protein \>1+ at screening, or urine protein 1+ that does not return to normal on repeat testing within 24 hours.
16. Definite tendency for gastrointestinal bleeding, including active local ulcerative lesions with fecal occult blood positivity of ++; history of melena or hematemesis within 2 months; high risk of bleeding such as grade \>=3 bleeding within 6 months, hemoptysis \>=2.5 mL per episode, imaging evidence of tumor invasion into major blood vessels, or bleeding risk deemed unacceptable by the investigator.
17. High risk of gastrointestinal perforation or fistula, including gastrointestinal perforation or active peptic ulcer within 6 months, or pelvic tumor invasion of the bladder or rectum with potential fistula risk as judged by the investigator.
18. Coagulation abnormality, including INR \>1.5 or APTT \>1.5 x upper limit of normal, with bleeding tendency.
19. Chronic unhealed wound or fracture; major surgery within 4 weeks; or severe traumatic injury, fracture, or ulcer within 4 weeks.
20. Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment or unlikely to comply with follow-up.