This is a single-arm, prospective, multicenter study evaluating a novel neoadjuvant treatment strategy for patients with early, mid-low rectal adenocarcinoma that is microsatellite stable (MSS). Instead of irradiating regional lymph nodes, we deliver short-course radiotherapy (25 Gy in 5 fractions) exclusively to the primary tumor ("lymph-node-sparing" approach), immediately followed by four 3-week cycles of capecitabine plus combined PD-1/CTLA-4 immune checkpoint inhibitors. Two weeks after completing chemo-immunotherapy, tumor response is assessed. Patients who achieve a clinical complete response may enter a "watch-and-wait" program; others will undergo local excision or total mesorectal excision (TME) as appropriate. The primary endpoint is the rate of complete response (clinical and pathological). Secondary endpoints include organ-preservation rate, 3-year local recurrence, 3-year disease-free and overall survival, toxicity, and quality-of-life measures. Results from a pilot study suggest that this regimen may substantially improve complete response rates while reducing radiation-related toxicity, potentially allowing more patients to avoid radical surgery and permanent stoma.
Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
Male or Female aged 18-80.
Patients diagnosed with low rectal cancer within 7 cm from the lower edge of the tumor to the anal verge by pelvic MRI and rectal ultrasound, the clinical stage is cT2-3N0M0.
Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
Patients with a previous history of malignant tumors besides rectal cancer.
Patients with distant metastases before enrollment.
Patients with metastatic regional or non-regional lymph nodes are assessed by MRI or CT.
Patients with obstruction, perforation, or bleeding that require emergency surgery.
Single group
Lymph-node-sparing short-course radiotherapy
RadiationThree-dimensional conformal or intensity-modulated radiotherapy targeting only the primary tumor bed (no regional lymph nodes), delivering a total dose of 25 Gy in 5 Gy fractions over five consecutive days.
Capecitabine
DrugOral capecitabine 1,000 mg/m² administered twice daily on Days 1-14 of each 21-day cycle, for a total of four cycles.
PD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection)
DrugIntravenous PD-1/CTLA-4 bispecific monoclonal antibody at 5 mg/kg every 3 weeks for four cycles, starting on Day 8 after completion of radiotherapy.
Clinical and pathological complete response rate (CR rate)
Proportion of enrolled patients who achieve a clinical complete response (cCR) on imaging, endoscopy, and biopsy and/or a pathological complete response (pCR) in surgical specimens (if resected) following lymph-node-sparing short-course radiotherapy combined with capecitabine and PD-1/CTLA-4 inhibitor.
Organ preservation rate
Proportion of patients who avoid total mesorectal excision (TME) and permanent stoma by remaining in watch-and-wait or undergoing only local excision.
3-year local recurrence rate
Proportion with tumor recurrence in the pelvis
Overall survival(OS）
The three-year overall survival of patients.
Adverse effects rate
Rate of radiotherapy, chemotherapy and immunotherapy related adverse events
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Sir Run Run Shaw Hospital
Lead sponsor
Sir Run Run Shaw Hospital, Qingchun Campus, Zhejiang University School of Medicine,
Sponsor institution
