Abstract C160: Risk stratification of red flag signs and symptoms for early-onset colorectal cancer detection

Background and Purpose: Early-onset colorectal cancer (CRC) incidence is increasing. In the absence of routine screening before age 45, early-onset CRC diagnosis often depends on timely work-up of symptoms to mitigate later-stage diagnosis and worse survival among younger patients. To inform risk-based diagnostic triage among symptomatic adults under age 50, we estimated associations between CRC risk and nine clinical signs and symptoms (hereafter referred to as symptoms). Methods: We conducted a retrospective cohort study using IBM® MarketScan administrative claims data (2017–2024). The analytic cohort included a representative national sample of 16.4 million commercially insured adults ages 18–49. We compared 5-year CRC risk among patients with nine symptoms—abdominal pain, abdominal distension, constipation, changes in bowel habit, diarrhea, nausea/vomiting, hematochezia, iron deficiency anemia (IDA), and anemia (not otherwise specified)—to that of asymptomatic individuals. We used Kaplan-Meier analysis to estimate cumulative incidence and derive absolute risk differences (RD) with 95% confidence intervals (CIs). To account for time-varying symptom exposure, we employed Poisson regression to calculate adjusted incidence rate ratios (IRR). Estimates of the number needed to scope to identify one CRC case (NNS) offer a clinical translation of observed risk differences, highlighting variation in diagnostic yield by symptom. We also conducted age-stratified analyses (18-34, 35-39, 40-44, and 45-49 years). Results: Among 16,377,276 individuals ages 18–49, 3,885,071 (23.7%) presented with at least one red flag sign or symptom. In the full sample, 5-year CRC risk was 0.08%. The symptoms most strongly associated with absolute CRC risk were hematochezia (RD: 0.43%, 95% CI: 0.41%-0.44%; NNS: 169), changes in bowel habit (RD: 0.36%, 95% CI: 0.33%-0.39%; NNS: 279), and anemia (RD: 0.21%, 95% CI: 0.20%-0.23%; NNS: 475). In Poisson regression analyses, hematochezia (IRR: 5.79, 95% CI: 5.53-6.07), changes in bowel habit (IRR: 3.20, 95% CI: 2.93-3.50), and IDA (IRR: 3.65, 95% CI: 3.09-4.31) were associated with increased CRC risk. Age-stratified analyses demonstrated increasing 5-year CRC risk with age across most symptoms. Among individuals presenting with hematochezia, for example, CRC risk rose from 0.07% (ages 18–34) to 0.45% (35–39), 0.62% (40–44), and 0.76% (45–49), with similar gradients observed for changes in bowel habit and anemia. Conclusions: Hematochezia, changes in bowel habit, and anemia were most strongly associated with early-onset CRC in adults under 50. Age-stratified findings suggest increasing CRC risk with age, with notably elevated CRC risk emerging at ages 35-39. These population-level risk estimates and age-stratified findings could support tailored, symptom-based triage in frontline settings, helping to guide diagnostic prioritization—particularly in contexts with limited colonoscopy access. Citation Format: Lola Van Doosselaere, Lin Liu, Matthew P. Banegas, Maria Elena Martinez, Samir Gupta, Cassandra Fritz, Joshua Demb. Risk stratification of red flag signs and symptoms for early-onset colorectal cancer detection [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C160.