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

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.