An artificial intelligence-assisted system versus white light endoscopy alone for adenoma detection in individuals with Lynch syndrome (TIMELY): an international, multicentre, randomised controlled trial.

BACKGROUND

Computer-aided detection (CADe) systems for colonoscopy have been shown to increase small polyp detection during colonoscopy in the general population. People with Lynch syndrome represent an ideal target population for CADe-assisted colonoscopy because adenomas, the primary cancer precursor lesions, are characterised by their small size and higher likelihood of showing advanced histology. We aimed to evaluate the performance of CADe-assisted colonoscopy in detecting adenomas in individuals with Lynch syndrome.

METHODS

TIMELY was an international, multicentre, parallel, randomised controlled trial done in 11 academic centres and six community centres in Belgium, Germany, Italy, and Spain. We enrolled individuals aged 18 years or older with pathogenic or likely pathogenic MLH1, MSH2, MSH6, or EPCAM variants. Participants were consecutively randomly assigned (1:1) to either CADe (GI Genius) assisted white light endoscopy (WLE) or WLE alone. A centre-stratified randomisation sequence was generated through a computer-generated system with a separate randomisation list for each centre according to block-permuted randomisation (block size 26 patients per centre). Allocation was automatically provided by the online AEG-REDCap database. Participants were masked to the random assignment but endoscopists were not. The primary outcome was the mean number of adenomas per colonoscopy, calculated by dividing the total number of adenomas detected by the total number of colonoscopies and assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04909671.

FINDINGS

Between Sept 13, 2021, and April 6, 2023, 456 participants were screened for eligibility, 430 of whom were randomly assigned to receive CADe-assisted colonoscopy (n=214) or WLE (n=216). 256 (60%) participants were female and 174 (40%) were male. In the intention-to-treat analysis, the mean number of adenomas per colonoscopy was 0·64 (SD 1·57) in the CADe group and 0·64 (1·17) in the WLE group (adjusted rate ratio 1·03 [95% CI 0·72-1·47); p=0·87). No adverse events were reported during the trial.

INTERPRETATION

In this multicentre international trial, CADe did not improve the detection of adenomas in individuals with Lynch syndrome. High-quality procedures and thorough inspection and exposure of the colonic mucosa remain the cornerstone in surveillance of Lynch syndrome.

FUNDING

Spanish Gastroenterology Association, Spanish Society of Digestive Endoscopy, European Society of Gastrointestinal Endoscopy, Societat Catalana de Digestologia, Instituto Carlos III, Beca de la Marato de TV3 2020. Co-funded by the European Union.

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Déclaration de conflit d'intérêts

Declaration of interests AL-R received payment or honoraria for lectures, presentations, speakers bureaus, or educational events from Boston Scientific, Fujifilm, NEC, and Olympus. AZG-G received grants from Fundación de la Sociedad Española de Endoscopia Digestiva and University Hospital of the Canary Islands. CH received a grant from AIRC under IG 2022 (ID 27843) project and consulting fees from Boston Scientific, Fujifilm, Olympus, and Odin. IP received consulting fees from Fujifilm and support for travels and attending meetings from Fujifilm and Casen. JN received grants or contracts from Deutsche Forschungsgemeinschaft (DFG), Deutsches Zentrum für Infektionsforschung (DZIF), Deutsche Krebshilfe, Hector-Stiftung, Bundesministerium für Bildung und Forschung (BMBF); and payment honoraria for lectures and presentations, travel, and attending meetings from Falk foundation. RB received research funding, speaker, and advisory fees from Medtronic; grants and contracts from Pentax, Digital Endoscopy, and Fujifilm; payment or honoraria for lectures and presentations from Medtronic, Pentax, and Fujifilm; receipt of equipment from Fujifilm and Pentax; and payment for expert testimony from Pentax. RB is also supported by a grant of Research Foundation Flanders. RH received grants or contracts from DFG, DZIF, Deutsche Krebshilfe, Hector-Stiftung, and BMBF; received payment for lectures and presentations from Falk Foundation and MSD Sharp&Dohme; and received equipment from Fujifilm. MP received speakers fees from Medtronic and advisory and speakers fees from Fujifilm and Olympus. FB received consultant fees from Olympus, Nouscom, Sysmex, and Norgine, and editorial fees from Elsevier. RJ received contracts from Medtronic through a research grant institution. All other authors declare no competing interests.