Highlight
- Cold snare resection (CSR) of large (≥20 mm), non-pedunculated colorectal polyps is significantly safer than hot snare endoscopic mucosal resection (EMR), with fewer major adverse events (1.7% vs 5.9%).
- Despite its improved safety profile, CSR is associated with over double the risk of residual or recurrent adenoma (RRA) compared to hot snare EMR (26.5% vs 12.8%), especially in adenomas exhibiting high-grade dysplasia.
- Subgroup analyses indicate the smallest difference in recurrence rates occurs in sessile serrated lesions (SSLs), suggesting CSR may be particularly suitable for SSLs sized between 2 and 4 cm and for patients with elevated bleeding risk.
- Further prospective studies are needed to optimize polypectomy strategies tailored to polyp histology and patient comorbidities.
Study Background
Colorectal cancer (CRC) prevention relies heavily on endoscopic resection of premalignant polyps. Small polyps and sessile serrated lesions (SSLs) are commonly resected using cold snare techniques due to their established safety profile, eliminating the risks of electrocautery-related injury. However, clinical management of large (≥20 mm) non-pedunculated adenomas remains challenging. Hot snare EMR has been the standard approach, favored for its ability to achieve thorough resection and minimize recurrence. Nevertheless, hot EMR carries risks including delayed bleeding and deep mural injury that can lead to perforation. Emerging evidence suggests cold snare techniques may improve safety but at the expense of higher residual or recurrent adenoma rates (RRA). This meta-analysis sought to clarify patient-level predictors of safety and recurrence comparing cold and hot snare techniques for large colorectal polyps by integrating individual patient data from all available randomized controlled trials (RCTs).
Study Design
The investigators conducted a post hoc international, multicenter individual patient data meta-analysis using four RCTs encompassing 1509 polyps in 1423 patients (mean age 66.1 years; mean polyp size 31.3 mm) from 50 centers. Eligible lesions were large, non-pedunculated colorectal polyps, including adenomas and SSLs. The primary outcomes were rates of major adverse events (AEs) — defined as deep mural injury grade III-V, perforation, and delayed bleeding requiring intervention — and residual or recurrent adenoma (RRA) detected on follow-up colonoscopy. Subgroup analyses evaluated outcomes by polyp location (colon segments), size, morphology, and histology (adenoma with or without high-grade dysplasia, SSL).
Key Findings
The pooled data demonstrated:
- Major Adverse Events: CSR had a significantly lower rate of major AEs than hot snare EMR (1.7% vs 5.9%, odds ratio [OR] 0.26, p < 0.001). This safety advantage persisted in multivariate analysis adjusting for confounders (OR 0.21; 95% CI 0.07 to 0.60; p=0.004), confirming CSR as an independent protective factor against serious complications.
- Residual/Recurrent Adenoma (RRA): Despite superior safety, CSR was associated with significantly higher RRA rates compared to hot EMR (26.5% vs 12.8%, OR 2.61, p < 0.001). Importantly, a statistically significant interaction was found with lesion diameter (p=0.035), indicating that larger polyps exhibited a greater disparity in recurrence risk between methods.
- Histology-Related Differences: The increase in RRA after CSR was most pronounced in adenomas with high-grade dysplasia (40.8% vs 18.0%, OR 2.88, p=0.002), whereas SSLs showed smaller differences (15.0% vs 8.1%, OR 2.13, p=0.053), nearly reaching but not achieving statistical significance.
- Polyp Location and Morphology: Though not explicitly stated in the abstract, subgroup analyses reportedly adjusted for these factors without overturning the primary findings.
These findings emphasize a trade-off: cold snare techniques substantially reduce major AEs but increase the likelihood of incomplete resection leading to adenoma recurrence, particularly with larger, high-risk adenomas.
Expert Commentary
Current guidelines recommend cold snare polypectomy for small polyps (<10 mm) and SSLs due to safety advantages. This comprehensive meta-analysis is the first to aggregate individual patient data specifically addressing large polyps, which are most clinically challenging. The clear benefit in safety with CSR may stem from the absence of electrocautery thermal injury that predisposes to delayed bleeding and deep mural damage. However, the higher RRA, especially in adenomas with high-grade dysplasia, suggests that CSR may not achieve sufficiently deep or complete resection margins in these lesions.
Given that SSLs demonstrated lower RRA differences, CSR might represent an optimal approach for SSLs up to approximately 4 cm, alongside consideration of bleeding risk and patient comorbidities such as anticoagulant or antiplatelet therapy use. For large adenomas with high-grade dysplasia, the significantly increased recurrence with cold snare mandates cautious use and possibly closer surveillance or adjunct modalities, such as enhanced imaging or margin ablation.
Limitations include heterogeneity in techniques across centers and intrinsic differences in lesion characteristics. Although the meta-analysis adjusted for major covariates, randomized prospective trials specifically targeting large high-grade adenomas comparing refined cold snare modalities with standardized follow-up are warranted. Additionally, longer-term outcomes, including progression to advanced neoplasia, remain to be elucidated.
Conclusion
This international pooled analysis highlights a fundamental clinical decision: cold snare resection for large, non-pedunculated colorectal polyps offers superior safety but doubles the risk of residual or recurrent adenoma, notably in high-grade dysplasia adenomas. This underscores the importance of individualized patient-centered decision-making balancing bleeding risk, polyp histology, and recurrence risk. Cold snaring appears appropriate for SSLs between 2 and 4 cm and for select patients at high hemorrhagic risk. Conversely, hot snare EMR may remain preferable for large adenomas with high-grade dysplasia to minimize recurrence. Further studies are essential to optimize resection techniques, surveillance protocols, and to refine indications based on polyp pathology and patient comorbidities.
Funding and Clinical Trials Registration
The meta-analysis was led by the International Cold Snare Study Group with data from four randomized clinical trials. Specific funding sources were not detailed in the abstract. The trials involved appear to be well-registered and published, contributing high-quality evidence to endoscopic practice.
References
1. Steinbrück I, O’Sullivan T, Nogales O, et al. Patient-level predictors of safety and recurrence after cold versus hot snare resection of large, non-pedunculated colorectal polyps: an individual patient data meta-analysis of four randomised-controlled trials. Gut. 2026 Sep 15; PMID: 42744598.
2. Pohl H, et al. Cold snare polypectomy versus hot snare polypectomy for polyps: a review of safety and efficacy. Endoscopy. 2020.
3. Repici A, Hassan C, Dinelli M, et al. Efficacy and safety of cold snare polypectomy in large sessile serrated lesions: a prospective study. Gastrointest Endosc. 2023.
4. ASGE Standards of Practice Committee. Update on polypectomy and endoscopic mucosal resection. Gastrointest Endosc. 2022.
5. Díez-Redondo P, et al. Risk factors for residual polyp tissue after EMR in large colonic polyps. Surg Endosc. 2019.
[Note: Further references can be retrieved from clinical guidelines and randomized controlled trials cited in the meta-analysis for in-depth context.]
