Hybrid endoscopic mucosal resection with endoscopic full thickness resection for large colonic lesions with focal suspicion of submucosal invasive cancer: an international, multicentre cohort study

Aims Large lateral spreading tumours (LST) in the colon with focal suspicion of submucosal cancer pose a clinical challenge. A hybrid approach combining endoscopic mucosal resection (EMR) for the non-suspicious parts and endoscopic full-thickness resection (eFTR) for the suspected invasive component may offer a viable alternative to endoscopic submucosal dissection or primary surgery, especially when deeper submucosal invasion is suspected. However, data on the safety and efficacy of this approach is scarce.

Methods Consecutive patients undergoing hybrid EMR-eFTR for suspected T1 colon cancer or non-lifting lesions with confirmed adenocarcinoma were selected from the prospective Dutch eFTR registry and three German centers (November 2015 to July 2024. Primary outcomes were technical success, R0 resection, and adverse events according to AGREE classification. Secondary outcome was cancer recurrence, assessed via surveillance endoscopies, CT-scans and CEA levels, as per local protocols. Technical success was defined as macroscopic en bloc resection of the suspected malignant component, R0 resection as carcinoma-free resection margins (> 0.1mm) of the eFTR specimen, low-risk T1 cancer as R0 resection without poor tumour differentiation, lymphovascular invasion and high-grade tumour budding.

Results A total of 59 patients (median age 72 years, 53% male) with a median lesion size of 30 mm (IQR 24-40) were included. Most lesions were located in the proximal colon (40/59, 68%), with 19 (32%) in the distal colon. The technical success rate was 54/59 (92%). Histology identified adenocarcinoma in 50/59 (85%) patients, including 37/50 (74%) T1 cancers (sm1: 35% [13/37]; sm2-3: 65% [24/37]), and 13/50 (26%)≥T2. Of the T1 cancers, 19/37 (51%) were considered low-risk. The overall R0 resection rate was 43/59 (73%), including 27/37 (73%) for T1 cancer (sm1: 92% [12/13]; sm2-3: 63% [15/24]). Incomplete resection of T1 cancer (n=10) was mainly based on positive lateral margins (10/10) rather than positive vertical margins (5/10). Adverse events occurred in 8/59 (14%) patients, including 2 (3%) perforations (1 immediate, 1 delayed) requiring surgery (Grade IIIb) and 1 (2%) delayed bleeding without bleeding focus at endoscopy (Grade IIIa). Following hybrid eFTR, 22/59 (37%) patients underwent completion surgery, while surveillance was initiated in the remaining 37 (63%). In the surveillance cohort (8 non-invasive, 16 low-risk T1, 9 high-risk T1, 4 T2), no locoregional cancer recurrences were detected over a median follow-up of 16 months (IQR 7-50). However, 1 patient with high-risk T1 cancer developed liver metastases at 41 months.

Conclusions This study shows promising technical and short-term oncological results for hybrid EMR-eFTR as an alternative treatment for large LSTs in the colon with focal T1 cancer suspicion. Given the presence of sm2-3 in the majority of T1 cancers, this approach could further push the boundaries for endoscopic resection. Prospective studies, preferably comparative, are needed to further establish the efficacy and oncological outcomes of this approach.