Cold snare endoscopic mucosal resection for large nonpedunculated adenomatous polyps: not all new techniques will develop in the future

The European Society of Gastrointestinal Endoscopy guidelines recommend conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥20 mm) laterally spreading tumors (LSTs) as a strong recommendation with high quality of evidence [1]. However, adverse events, such as perforation, delayed bleeding, and post-polypectomy syndrome remain clinical concerns. Recently, the cold snare polypectomy technique, which is recommended for the removal of small polyps (6–9 mm) [1], has been extended to LSTs by employing submucosal injection and sequential piecemeal cold snare resection. Cold snare EMR (CS-EMR) appears to reduce the adverse events primarily related to electrocautery. However, it inevitably results in superficial and piecemeal resection of large lesions, which may increase local recurrence. There is a paucity of data comparing hot EMR and CS-EMR for resection of large flat LSTs.

“The clinical indications for extensive cold snare EMR may be limited to serrated lesions without dysplasia.”

Given this background, in this issue of Endoscopy, Nogales et al. present their findings from a multicenter randomized controlled trial (RCT), which was conducted to compare CS-EMR with hot EMR for large flat nonpedunculated colonic lesions [2]. The primary end point was the recurrence rate. A total of 229 patients were randomized to receive CS-EMR or hot EMR of lesions with a median size of 25 mm, 75% of which were adenomas. At the first follow-up at 6 months, the recurrence rate in the CS-EMR group was 33.0% vs. 16.2% with hot EMR (P = 0.004); the absolute risk difference was 16.81% (95%CI 5.63% to 27.99%; P = 0.004) in the intention-to-treat analysis. Recurrence in lesions ≥30 mm was 43.1% with CS-EMR and 18.2% with hot EMR. The en bloc resection rate was statistically higher in the hot EMR arm than in the CS-EMR arm in both the intention-to-treat analysis (23.7% vs. 1.7%; P < 0.001) and per-protocol analysis (24.3% vs. 0%; P < 0.001). Furthermore, the median number of fragments was significantly greater with CS-EMR than with hot EMR (6 vs. 3; P < 0.001). There were no differences in adverse events, with delayed bleeding in 3.5% of the hot EMR arm and 2.6% of the CS-EMR arm, and no perforations in either arm. The trial was prematurely stopped as recommended by the Independent Safety Committee, and the P value met the O’Brien–Flemming criteria for the intention-to-treat and per-protocol populations.

This RCT highlighted two clinical drawbacks of CS-EMR for large flat adenomatous polyps. First, the en bloc and R0 resection rates in the CS-EMR arm were considerably lower, resulting in a greater number of piecemeal fragments, and, consequently, a significantly higher local recurrence rate compared with hot EMR. These findings underscore the technical limitation of CS-EMR, requiring intensive follow-up and repeated endoscopic resection, thereby increasing the socioeconomic burden. This drawback is supported by a previous similar RCT by O’Sullivan et al. [3]. Although this latter study included routine margin thermal ablation after resection, recurrence was significantly greater after CS-EMR than after hot EMR (16/87 [18.4%] vs. 1/90 [1.1%]; relative risk 16.6, 95%CI 2.24–122; P < 0.001) [3]. While the risk of adverse events is acceptable and consistent with the data from a previous RCT by Steinbrück et al. [4], local recurrence is much more clinically relevant than the adverse events.

The second concern is that multiple fragments from piecemeal resection may lead to inaccurate histologic analysis. As described by the authors in the methods section, it is essential to perform detailed preoperative evaluation using high-definition white-light endoscopy, magnifying virtual endoscopy, or chromoendoscopy, and to analyze lesion characteristics based on the Narrow-Band Imaging International Colorectal Endoscopic classification, Japan Narrow Band Imaging Expert Team classification, or pit pattern classification. However, the combination of piecemeal resection with multiple fragments and superficial resection with CS-EMR, which does not include the muscularis mucosa and submucosa, logically reduces the quality of histologic analysis. Consequently, clinicians might not receive accurate feedback from the histology. Although the authors reported that 75% of lesions were adenomas despite large lesions >20 mm, there is a concern that a carcinoma component might be missed in large flat adenomatous lesions, particularly in the CS-EMR arm where piecemeal resection with multiple fragments is performed. This study was terminated early, and the long-term outcomes could not be fully assessed. There remains a risk of invasive recurrence after piecemeal EMR due to the underdiagnosis of the depth of invasion and the potential for missed lymphovascular invasion [5]. This negative RCT underscores that not all new techniques will develop in the future. The clinical indications for extensive CS-EMR may be limited to serrated lesions without dysplasia.

It should be noted that local recurrence could be mainly explained by piecemeal resection. Although thermal margin ablation as recommended by the guidelines may help to reduce local recurrence [1], the inherent limitations of piecemeal resection still compromise the quality of histologic analysis, even in LSTs. Colorectal endoscopic submucosal dissection (ESD) offers en bloc and R0 resection regardless of lesion size and location [6]. ESD was pioneered in Japan and over the past decade has achieved widespread acceptance as a minimally invasive resection technique in Western countries [7]. With the growing utility of ESD, new and exciting research has followed. A recent RCT from France showed the local recurrence rate of neoplastic tissue was significantly lower with ESD than with EMR including piecemeal resection [8].

Clinicians should recognize the balance between the limits of current resection techniques and the potential for further development and should reconsider how we can provide better clinical practice.

Publication History

Article published online:
14 May 2025

• References

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