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FAECAL IMMUNOCHEMICAL TEST TO DETECT COLORECTAL NEOPLASIA IN LYNCH SYNDROME – A PROSPECTIVE MULTICENTRE STUDY

Date
May 19, 2024

Objective
Colonoscopy surveillance for Lynch syndrome is burdensome and post-colonoscopy colorectal cancers (CRCs) still occur. The non-invasive faecal immunochemical test (FIT) might guide optimal colonoscopy intervals.

Design
Prospective, multi-centre observational study in which individuals with Lynch syndrome performed a quantitative FIT prior to high-quality surveillance colonoscopy. Diagnostic performance of FIT at various thresholds ≤20 μg/g was assessed for relevant neoplasia, including advanced neoplasia (CRC, advanced adenomas [AA] and advanced serrated lesions [ASL]) and non-advanced adenomas (NAA).

Results
Of the 217 included individuals (59% female, median age 51y), 4 had CRC, 5 AA, 4 ASL and 57 NAA as most relevant neoplasia. The lowest FIT positivity threshold (2.55 μg/g, 14% positivity rate) maximised detection: 4/4 CRCs, 4/5 AA, 1/4 ASL and 9/57 NAA were detected, resulting in a sensitivity and negative predictive value (NPV) of, respectively, 89% and 99% for CRC plus AA, 69% and 97% for advanced neoplasia, and 26% and 72% for all relevant neoplasia (91% specificity for all groups). At equal sensitivity and NPV, specificity for advanced neoplasia optimised to 94% at threshold 4.08 μg/g. Per 100 FITs at threshold 4.08 μg/g, 11 individuals would test positive and thus be referred for colonoscopy, 2 individuals with advanced neoplasia would be missed and 3 individuals would need colonoscopy to detect 1 advanced neoplasia.

Conclusion
FIT ≤ 4.08 μg/g may be a safe strategy to postpone colonoscopy in approximately 9 out of 10 individuals with Lynch syndrome. Large validation studies that also provide gene mutation-specific outcomes should be prioritised.
Diagnostic accuracy of the faecal immunochemical test in Lynch syndrome

Diagnostic accuracy of the faecal immunochemical test in Lynch syndrome

Outcomes per 100 individuals with Lynch syndrome tested by faecal immunochemical test at different thresholds

Outcomes per 100 individuals with Lynch syndrome tested by faecal immunochemical test at different thresholds


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