S668 Comparative Effectiveness of Stool-Based Screening vs Colonoscopy on Long-Term Colorectal Cancer Incidence: A Retrospective Cohort Analysis

Introduction: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally. Colonoscopy is the gold standard for screening due to its ability to detect and remove precancerous lesions. However, its invasive nature has led to increased use of stool-based screening tests—including guaiac fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and stool DNA testing—for their convenience and potential to improve adherence. This study evaluated long-term CRC incidence and mortality among individuals screened exclusively by stool-based methods compared to those undergoing colonoscopy. Methods: We conducted a retrospective cohort analysis using the TriNetX database. Patients aged 45–80 years with no prior CRC diagnosis or history of colonoscopy were grouped based on stool-based screening method (gFOBT or FIT DNA stool ) and matched 1:1 with a colonoscopy cohort. Propensity score matching adjusted for demographics (age, sex, race) and comorbidities (alcohol use, tobacco use, diabetes, family/personal malignancy history, and lipid disorders). Primary outcomes included subsequent CRC incidence and CRC-related mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated; significance was set at P < 0.05. Results: Following matching, the FIT (n = 1,829,596) and gFOBT (n = 1,517,107) groups had significantly higher CRC incidence than the colonoscopy group (FIT: odds ratio [OR] 1.65, 95% CI 1.58–1.74, P < 0.001; gFOBT: OR 1.84, 95% CI 1.75–1.94, P < 0.001). The stool DNA group (n = 373,740) showed no significant difference in CRC incidence versus colonoscopy (OR 1.02, 95% CI 0.90–1.16, P = 0.711). CRC mortality was higher in the FIT (OR 1.63, 95% CI 1.61–1.65, P < 0.001) and gFOBT (OR 1.84, 95% CI 1.81–1.86, P < 0.001) cohorts, but significantly lower in the stool DNA group (OR 0.51, 95% CI 0.49–0.52, P < 0.001). Conclusion: Colonoscopy remains the most effective screening modality, given its ability to detect and remove precancerous lesions directly. Although stool-based tests are less invasive and may improve screening uptake, reliance on FIT or gFOBT alone was associated with higher CRC incidence and mortality. In contrast, stool DNA testing demonstrated comparable outcomes to colonoscopy and even lower CRC mortality, suggesting its potential as a robust noninvasive alternative in CRC screening strategies.