Abstract PR014: FIT for red flag signs and symptoms of early onset colorectal cancer: low value or viable diagnostic tool?

Purpose: Early-onset colorectal cancer (EOCRC) incidence is rising in a predominantly symptomatic population of young adults. Effective triage tools are needed to identify high-risk individuals in this relatively low incidence population. We examined fecal immunochemical test (FIT) use among adults ages <50 with red flag signs and symptoms for EOCRC and evaluated whether FIT use is predictive of EOCRC risk. Methods: Retrospective cohort study of US Veterans (ages 18-49) receiving Veterans Health Administration (VHA) care during 1999-2022 with a documented EOCRC red flag sign or symptom (abdominal distension, abdominal pain, anemia [non-specific and iron-deficiency], change in bowel habits, constipation, diarrhea, hematochezia, nausea/vomiting) based on International Classification of Diseases, 9th (ICD-9) or 10th (ICD-10) Revision codes, or lab results. The primary exposure was FIT uptake and result, documented via lab results, shown as a three-level variable (no FIT use, negative FIT or positive FIT). The primary outcome was EOCRC diagnosis, derived from linkages to the VA Oncology Domain and National Death Index. Covariates included age at symptom presentation, sex, race and ethnicity, and number of symptoms within 60 days of first symptom presentation. Participants entered the study at first symptom onset and were followed until the first of: incident or fatal EOCRC diagnosis, non-EOCRC-related death, 2 years follow-up, age 50 or December 31, 2022. We derived cumulative CRC incidence estimates using Kaplan-Meier estimation. Multivariable, mixed-effects Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for CRC risk among those who received a FIT test. Results: Among 751,116 Veterans, 38,019 (5.1%) received a FIT. The most common symptoms yielding a FIT were abdominal pain (29.6%), anemia (20.4%), hematochezia (18.5%), and diarrhea (16.4%). Approximately 76% of patients who received a FIT had one symptom at presentation. Among 38,019 patients who received a FIT, 6,191 (16.3%) had a positive finding. Approximately 1,295 (21%) of 6,191 FIT-positive patients received a diagnostic colonoscopy compared to 46,693 (6.6%) of 713,097 non-FIT patients. After two years of follow-up, patients with a positive FIT had a 1.44% cumulative EOCRC incidence (95% CI: 1.12%-1.77%), compared to a 0.12% among those with a negative FIT (95% CI; 0.08%-0.16%) and 0.12% among those who did not receive a FIT (95% CI: 0.12%-0.13%). The findings correspond to an aHR for EOCRC of 12.81 (95% CI: 8.47-19.36) for FIT-positive patients compared to those with a negative FIT. Conclusions: Among adults ages 18-49 presenting with a red flag sign or symptom to VHA care, FIT use was low. However, a positive FIT result was linked to a substantially elevated EOCRC risk relative to a negative result. To address potential concerns about generalizability, future research should confirm whether systematic use of FIT as a clinical triage tool could help identify symptomatic adults at high EOCRC risk who need a diagnostic colonoscopy. Citation Format: Daniel Sabater Minarim, Kylie Morgan, Lin Liu, Matthew P. Banegas, Maria Elena Martinez, Samir Gupta, Josh Demb. FIT for red flag signs and symptoms of early onset colorectal cancer: low value or viable diagnostic tool? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr PR014.