Colorectal Cancer in the U.S., 1999–2021: Declining Rates, Rising Concerns, and Persistent Disparities

Background: Colorectal cancer (CRC) incidence and mortality have declined in the United States over the past two decades, yet disparities persist by age, sex, race/ethnicity, and geography. To characterize population-level survival signals, we examined trends in age-adjusted incidence rates (AAIR), mortality rates (AAMR), and the mortality-to-incidence ratio (AAMIR) from 1999 to 2021, stratified by key subgroups. Methods: This retrospective analysis utilized de-identified data from the CDC WONDER United States Cancer Statistics database, encompassing incident CRC cases (SEER codes 21041–21052) and deaths (ICD-10 codes C18–C20) in adults aged 20 years and older. Age-adjusted rates (per 100,000, 2000 U.S. standard population) and AAMIR were calculated using Stata 17.0. Joinpoint regression identified trends (annual or average annual percent change APC/AAPC, p < 0.05). Results: Among 3,489,881 cases and 1,225,986 deaths, AAIR decreased from 78.24 (1999) to 50.79 (2021; AAPC: −2.20%, 95% CI: −2.52 to −1.89), AAMR decreased from 29.34 to 17.92 (AAPC: −2.33%, −2.46 to −2.20), and AAMIR from 0.375 to 0.353 (AAPC: −0.08%, −0.47 to 0.30; p = 0.669). Women showed a significant AAMIR decline (AAPC: −0.29%), unlike men (AAPC: 0.07%). Young adults (20–39 years) had rising AAIR (AAPC: 2.42%) and AAMR (0.87%) but improving AAMIR (AAPC: −1.71%). Non-Hispanic Black individuals had the highest AAMIR (0.400 in 2021; AAPC: −0.54%). The Northeast had the most favorable AAMIR trend (AAPC: −0.40%), while the Midwest, South, and West were stable. States like New Jersey and Massachusetts achieved low AAMIR (0.292 and 0.304 in 2021), contrasting with Nebraska and Arizona (0.402 in both). Conclusions: Although colorectal cancer incidence and mortality have declined substantially in the United States from 1999 to 2021, the mortality-to-incidence ratio improved only marginally and remained markedly uneven across subgroups. Targeted interventions—enhancing screening and treatment access for men, racial/ethnic minorities, younger adults, and high-burden regions and states—can promote equitable outcomes.