FITting noninvasive testing into Lynch syndrome colorectal cancer surveillance: a multicenter, prospective trial

PROJECT SUMMARY/ABSTRACT Lynch syndrome (LS), the most common inherited cause of colorectal cancer (CRC) affecting ~1.2 million Amer- icans, carries 3-8x higher lifetime CRC risk than the general population. Colonoscopy starting early in adulthood and repeated yearly or biennially is the only recommended surveillance strategy which translates into ~25-50 lifetime colonoscopies. This intensive colonoscopy surveillance is not ideal because: a) CRC risk varies widely by LS gene and age, b) colonoscopies are invasive, costly, and not readily accessible to all patients, and c) adherence is suboptimal. Personalized surveillance strategies in LS that integrate non-invasive tests with colon- oscopy would address limitations and barriers in current clinical practice but have not been previously studied. To address these gaps, this multi-center, prospective trial will examine performance of fecal immunochemical test (FIT) in LS patients undergoing colonoscopy surveillance. In addition to measuring FIT test characteristics (specificity, sensitivity, negative and positive predictive value), this study will examine LS patients' attitudes and acceptability of non-invasive tests (Aim 1). The proposal will evaluate personalized surveillance strategies in LS that integrate non-invasive tests and colonoscopy using simulation modeling (Aim 2). An important deliverable is the 1st well-annotated, prospective LS biobank in the US for future studies of promising biomarkers and clinical outcomes (Aim 3). This study is timely because of the unique opportunity to harmonize data with the UK “FIT for Lynch” study that began recruitment in 2023 in order to evaluate FIT performance in a large, international LS cohort. Taken together, the proposal is significant because it has potential to change paradigms of CRC surveil- lance in order to improve the lives and longevity of LS patients.