This open-label, multicenter, randomized controlled trial involved 196 patients with pathologically confirmed, previously untreated, resectable MSI-L or MSS/pMMR ultra-low rectal adenocarcinoma. Patients were randomly assigned (1:1) to two groups to receive concurrent chemoradiotherapy followed by 4-6 cycles of chemotherapy ± tislelizumab. After treatment, patients who achieved complete clinical response (cCR), including those who reached pCR after local excision, or near cCR with pCR after local excision, were recommended to continue with 4-2 cycles of chemotherapy ± tislelizumab, followed by a watch-and-wait approach. Patients evaluated as incomplete responders were recommended for total mesorectal excision (TME) surgery. The primary endpoint is the anus preservation rate, while secondary endpoints include CR rate, 1-year/2-year/3-year organ preservation rates, 1-year/2-year/3-year EFS rates, and 1-year/2-year/3-year OS rates, etc.
Able to provide written informed consent, understand, and comply with the requirements and evaluation schedule.
Age ≥18 and ≤75 years old.
Histologically confirmed rectal adenocarcinoma.
Immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6, and PMS2), or PCR/NGS confirmed MSI-L or MSS.
Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma.
Previously received treatment for rectal cancer or have evidence of distant metastasis.
Presence of the following high-risk factors assessed by MRI: MRF+, EMVI+, cN2, positive lateral lymph nodes, T3d.
Presence of or at high risk for obstruction, perforation, or bleeding.
Parallel
Long-course chemoradiotherapy
Radiation45-50.4 Gy in 25-28 fractions to the pelvis on Days 1-5 each week. Capecitabine at a dose of 825 mg/m², taken orally twice daily (bid), 5 days per week during radiotherapy.
Tislelizumab combined with the CAPOX regimen
DrugTislelizumab 200 mg IV on Day 1 of each 21-day cycle. Capecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle. Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.
CAPOX regimen
DrugCapecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle. Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.
Anus preservation rate
Defined as the anus preservation rate in the efficacy-evaluable analysis set of patients, as assessed by the investigators.
Complete Response rate (CR Rate)
Defined as the proportion of participants with clinical complete response (cCR) and pathologic complete response (pCR), determined by the investigators.
1/2/3-Year Organ-Preservation Rate
Defined as the proportion of participants who survived and did not undergo TME at 1, 2, and 3 years.
1/2/3-Year EFS Rate
Defined as the proportion of participants who did not develop local recurrence, distant metastasis, new invasive primary lesions of colorectal cancer, or death at 1, 2, and 3 years.
1/2/3-Year OS Rate
Defined as the proportion of participants who survived at 1, 2, and 3 years.
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