High-definition (HD) colonoscopy is the gold standard for early diagnosis and treatment of lower gastrointestinal neoplasms, with the adenoma detection rate (ADR) serving as a key quality indicator due to its inverse correlation with colorectal cancer incidence. ADR is influenced by operator expertise, fatigue, and human error, which may be mitigated by advanced imaging technologies such as computer-aided detection (CADe). CADe systems provide real-time visual and auditory alerts for suspected polyps and have been shown to increase ADR, though their effectiveness under different operator conditions (high- vs. low-volume, fatigue-related performance, impact on polyp detection rate [PDR] and withdrawal time) remains unclear. This multicenter, prospective, national, open-label randomized trial (6 Italian centers) will compare HD-Iscan colonoscopy with and without CADe assistance (1:1 allocation), with primary endpoint ADR and secondary endpoints including PDR, withdrawal time, and performance stratified by operator fatigue. Eligible patients (aged 40-80, undergoing screening, surveillance, or diagnostic colonoscopy) will be recruited consecutively, with exclusions for prior colonic resection, recent diverticulitis, inflammatory bowel disease, familial polyposis, inadequate bowel preparation, complete colonoscopy within 5 years, inability to consent, or unsafe ongoing antithrombotic therapy. Colonoscopies will follow ESGE guidelines with standard split-dose PEG preparation; all polyps will be resected and documented. Operator allocation to high- (≥200 colonoscopies/year) or low-volume (<200/year) groups will follow routine clinical scheduling, with stratified analyses performed. The trial involves no investigational drugs or additional invasive procedures, and no adverse events are anticipated beyond those inherent to colonoscopy.

Inclusion criteria:

• Age 40-80 years, any sex
• Indication for screening, surveillance, or diagnostic colonoscopy (e.g., anemia, abdominal symptoms)
• Written informed consent

Exclusion criteria:

• Previous (even partial) colon resection or colonic stenosis
• Acute diverticulitis within 4 weeks
• Inflammatory bowel disease, familial adenomatous polyposis, or microscopic colitis
• Complete colonoscopy within 5 years
• Inadequate suspension of antithrombotic/antiplatelet therapy (per ESGE guidelines)
• Inability to provide consent
• Inadequate bowel preparation (Boston Bowel Preparation Scale <2 in any segment)

Individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).

Researchers who provide a methodologically sound proposal.