Initial reports have described rectal endoscopic knife-assisted full-thickness resection (kFTR) as a novel technique for achieving R0 resection in deeply invasive rectal cancer or technically challenging rectal lesions, offering a potential alternative to surgery and reducing associated morbidity and mortality.^1,2 This study aimed to evaluate the feasibility, safety, and technical outcomes of rectal kFTR in an international, multicenter cohort.

We conducted an observational cohort study of consecutive patients undergoing rectal kFTR at 16 centers across 5 continents between April 2017 and April 2025. Eligible patients had rectal lesions with suspected deep submucosal invasion, severe submucosal fibrosis, or subepithelial pathology. Primary outcomes were technical success, en-bloc and R0 resection rates, and adverse events (AEs). Secondary outcomes included length of hospital stay, rectal preservation, and recurrence. Risk factors for AEs were assessed using univariate and multivariate logistic regression.

97 patients (mean age 66 years [IQR 58-74]; 57.7% male; 79.1% ASA I/II) were included. The median lesion size was 35 mm [IQR 25-50].

kFTR was performed for suspected deep invasion (59; 60.8%), severe fibrosis (30; 30.9%), and subepithelial lesions (8; 8.2%). 

The technical success rate was 97.9% (95/97), while en-bloc and R0 resection rates were 96.9% and 79.4%, respectively. 31 (32.0%) lesions were T2 adenocarcinomas, 27 (27.8%) non invasive/T1 adenocarcinomas, 28 (28.9%) T1 sm2-3 adenocarcinomas, 8 subepithelial lesions (8.2%), 3 (3.1%) T3 adenocarcinomas.

Overall, 19 adverse events occurred in 15/97 (15.5%) patients: 12 grade I, 2 grade II, and 5 grade III per AGREE classification. Delayed bleeding occurred in 4 (4.1%) patients, and post-procedural pain in 7 patients (7.2%). One patient required surgery for a recto-vaginal fistula. Increasing lesion size was the only risk factor independently associated with a higher risk of adverse events (OR 1.05, 95% CI 1.02–1.09, p = 0.003).

Median procedural time was 135 minutes (IQR 100–180), and median hospital stay was 1 day (IQR 0.5–3). Rectal preservation was achieved in 75.9% (22/29) of patients with T1 adenocarcinoma and 45.2% of T2 (14/31) adenocarcinomas.

Among 59 patients with adenocarcinoma and available follow-up (median 12 months (IQR 6 - 23.5)), 3 (5.1%) experienced loco-regional recurrences, and 1 (1.7%) had distant metastasis. There were no cancer-related deaths.

 Table 1. Technical outcomes of endoscopic knife-assisted full-thickness resection across different histopathological groups.

kFTR appeared to be a feasible and safe technique for excising deeply invasive adenocarcinomas and complex fibrotic or subepithelial rectal lesions in expert centres. Rectal kFTR may serve as an alternative to device-assisted endoscopic full-thickness resection and local surgical excision, potentially avoiding radical surgery in highly selected patients.