Characterizing symptom patterns in early-onset colorectal cancer: insights from a national inpatient analysis

While colorectal cancer (CRC) incidence overall is declining, early-onset CRC (EOCRC, diagnosed before age 50) continues to rise. In response, screening guidelines were lowered from age 50 to 45 in 2021. However, many EOCRC cases still occur under age 45, highlighting the need to identify high-risk individuals beyond current criteria. We hypothesized that EOCRC presents with distinct symptom profiles compared to late-onset CRC (LOCRC).

We analyzed 2020-2022 National Inpatient Sample data, performing 1:1 age-matched comparisons between CRC patients and controls without CRC. Symptoms were defined using ICD-10 codes. Adjusted odds ratios (aORs) were calculated and stratified by age and sex. Bonferroni correction was applied for 12 symptom groups (p < 0.004).

Among 18,017 EOCRC hospitalizations, several symptoms demonstrated differential associations compared to LOCRC, including constipation, iron-deficiency anemia, and hematochezia. Data-driven stratification revealed that constipation showed the strongest divergence between EOCRC and LOCRC (aOR 2.50 vs. 1.12), particularly among women under 40 (aOR 5.72; p < 0.001). Colon cancer was identified in 1.31% of constipation-related hospitalizations in adults aged 40-44, comparable to the 1.07% incidence among all hospitalizations in adults 45-49.

Symptom pattern analysis from a large national inpatient cohort demonstrates distinct clinical presentations of EOCRC. Constipation showed a stronger association in younger adults, particularly women, suggesting a potential role in identifying higher-risk presentations. However, these findings reflect hospitalized encounters and may be enriched for patients with more advanced or complicated disease rather than early-stage detection. Importantly, despite significant relative associations, the absolute prevalence of colorectal cancer among constipation-related hospitalizations remained low, underscoring the need for cautious interpretation and further prospective validation.

EOCRC: In this unstructured, symptom-driven national analysis, constipation emerged as a disproportionately stronger association with early-onset colorectal cancer (EOCRC) than with late-onset disease. These findings suggest that data-driven symptom evaluation can uncover clinically relevant signals to inform earlier recognition and diagnosis of EOCRC.