Local Advanced Rectal Cancer

This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone. After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.

This is a randomized, controlled clinical trial based on prior exploratory findings, designed to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with tafolecimab(an anti-PCSK9 inhibitor) and sintilimab (an anti-PD-1 inhibitor) versus neoadjuvant chemoradiotherapy combined with sintilimab alone in patients with pMMR/MSS locally advanced rectal cancer. The primary endpoint is the complete response (CR) rate, including the pathological complete response (pCR) rate in patients who undergo surgery after neoadjuvant therapy, and the clinical complete response (cCR) rate in patients managed with a watch-and-wait strategy. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), downstaging rate, R0 resection rate, tumor regression grade, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), and safety.

The purpose of this multicenter randomized non-inferiority trial is to evaluate the safety of low anterior resection for rectal cancer performed with versus without a diverting stoma in patients with a low predicted risk of colorectal anastomotic leakage. The primary objective is to determine whether the rate of anastomotic leakage within 30 days after surgery in the no-stoma group is non-inferior to that in the diverting stoma group. The secondary objectives include comparison between groups regarding: Stoma rate at 1 year after surgery; Quality of life at 30 days and 1 year (EORTC QLQ-C30, EORTC QLQ-CR29, and LARS score); Short-term postoperative outcomes, including postoperative day metrics, length of hospital stay, and complications graded according to the Clavien-Dindo classification; Reoperation rates within 30 days and 1 year. Participants will include adult patients with mid- or low-rectal adenocarcinoma who are scheduled for radical minimally invasive total mesorectal excision and have a predicted risk of anastomotic leakage \<10% according to the study risk model.