“Divergent paths in the right colon”: A 24-year analysis of appendiceal cancer versus cecal cancer mortality in the United States (1999-2023) and age and sex disparities.

e15712 Background: Despite their anatomical proximity, appendiceal and cecal cancers represent distinct biological entities with divergent incidence patterns. While right-sided colon cancer mortality has generally benefited from screening advances, appendiceal cancer remains largely occult. We analyzed US mortality trends over 24 years to quantify the widening gap between the dramatically rising appendiceal cancer against the backdrop of stable cecal cancer mortality, specifically examining the impact of early-onset disease and sex disparities. Methods: We utilized the CDC WONDER database to identify cancer-specific mortality for appendiceal (ICD-10: C18.1) and cecal (ICD-10: C18.0) malignancies from 1999 to 2023. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated. Joinpoint regression analysis was performed to calculate the Average Annual Percent Change (AAPC). Cohorts were stratified by sex and age to assess disparities in early-onset mortality. Results: A total of 21,120 deaths were identified (Appendix: 11,971; Cecum: 9,149). From 1999 to 2023, overall appendiceal AAMR increased significantly (AAPC: +4.814, CI: 4.09-5.54; p<0.01), whereas cecal mortality remained stable (AAPC: 1.17, CI: -2.07-4.54; p>0.05). The divergence was most pronounced in the early-onset cohort (<50 years): appendiceal mortality rose sharply (AAPC: [+4.71, CI: 3.42-5.12; p<0.001), significantly outpacing cecal trends. Sex-stratified analysis revealed that while men had higher absolute mortality rates in both groups, the rate of increase for appendiceal cancer was steeper in men (AAPC: 5.008, CI: 4.31-5.71; p<0.01). Conversely, cecal mortality in older adults (≥50) showed a stable trend (AAPC: 0.05, CI: -1.68-1.89; p>0.05), while appendiceal cancer revealed a stark increase (AAPC: 5.91, CI: 4.90-6.92; p<0.01) reflecting screening efficacy not seen in appendiceal cohorts. Conclusions: This 24-year analysis confirms a significantly rising mortality burden for appendiceal cancer, sharply contrasting with the stability of cecal cancer, challenging the practice of grouping these entities in epidemiological reporting. The alarming rise in early-onset appendiceal mortality highlights a critical public health gap, as current colorectal screening guidelines fail to detect these malignancies. Distinct clinical vigilance and research into environmental or biological drivers of appendiceal carcinogenesis are urgently warranted. Cecal vs appendiceal cancer mortality trend 1999-2023. Average Annual Percent Change (AAPC) Cohort Lower Endpoint Upper Endpoint AAPC Lower CI Upper CI Test Statistic~ P-Value~ Cecum-Malignant neoplasms-3 JP 1999 2023 1.1787 −2.0782 4.5439 0.7019 0.482725 Appendix-Malignant neoplasms-1 JP 1999 2023 4.8145* 4.0938 5.5402 13.3572 <0.000001 * = Statistical significance at p<0.05.