Low-dose radiotherapy

This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Tumor response will be assessed after two cycles using endoscopy and pelvic magnetic resonance imaging (MRI). Participants with non-progressive disease, defined as partial response (PR) or stable disease (SD), will receive no further low-dose radiotherapy and will continue pucotenlimab plus CAPEOX for cycles 3 and 4. Participants with local progressive disease, defined as enlargement of the rectal tumor, will receive salvage chemoradiotherapy according to the center's standard operating procedures. Participants who develop distant metastases will receive further treatment determined by a multidisciplinary team (MDT). After four cycles, participants who achieve a clinical complete response (cCR) may enter a watch-and-wait strategy. Participants without cCR and without progressive disease will undergo radical surgery according to total mesorectal excision (TME) principles. Participants with progressive disease will receive individualized treatment determined by the MDT.