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

Lancet Gastroenterol Hepatol. 2024 Sep;9(9):802-810. doi: 10.1016/S2468-1253(24)00187-0. Epub 2024 Jul 19.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adenoma* / diagnosis
  • Adenoma* / pathology
  • Adult
  • Aged
  • Artificial Intelligence*
  • Colonoscopy* / methods
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Diagnosis, Computer-Assisted / methods
  • Early Detection of Cancer / methods
  • Female
  • Humans
  • Male
  • Middle Aged

Associated data

  • ClinicalTrials.gov/NCT04909671