Background/Objectives: Large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) are challenging lesions with a variable, yet non-negligible risk of advanced neoplasia. While correct management is therefore mandatory, a discrepancy often persists between guideline recommendations and daily endoscopic practice. To bridge this gap, we performed a comprehensive and structured review of the available evidence, aiming to synthesize the current knowledge and provide practice-oriented guidance for the optimal management of LNPCPs throughout the diagnostic-therapeutic pathway. Methods: A comprehensive literature review was independently performed. We systematically searched PubMed and Google Scholar up to December 2025. After the literature review, we identified the most clinically relevant and controversial aspects in the endoscopic management of LNPCPs. These key areas were then translated into focused, practice-oriented clinical questions. Results: We formulated 14 practice-oriented questions addressing the key steps of endoscopic management of LNPCPs. These questions cover the entire diagnostic-therapeutic pathway, including lesion detection, morphological characterization, optical diagnosis and risk stratification for submucosal invasion, selection of the optimal resection technique, and post-resection surveillance strategies. For each question, the current evidence was synthesized to provide concise, clinically applicable answers aimed at supporting real-world endoscopic decision-making. Conclusions: The endoscopic management of LNPCPs requires a structured and evidence-based approach that integrates accurate assessment, appropriate technique selection, and tailored post-resection surveillance. By framing current evidence into focused, practice-oriented questions, this review aims to bridge the gap between guideline recommendations and real-world endoscopic practice. The proposed framework may support endoscopists in daily clinical decision-making, promoting the appropriate use of advanced endoscopic techniques and ultimately improving patient outcomes.
Capelli et al. (2026) studied this question.