The Incidence of Rectal Neuroendocrine Tumors Is Increasing in Younger Adults in the US, 2001–2020

Simple Summary Prior data showed an increasing incidence of rectal neuroendocrine tumors (RNET) in the US. There are limited comprehensive recent data on RNET incidence and time-trends among demographic-specific populations. The aim of this study was to evaluate recent age-specific RNET incidence rates and time-trends in demographic- and tumor-specific populations, using the United States Cancer Statistics (USCS) data covering ~98% of the US population between 2001 and 2020. Our nationwide analysis including 59,846 patients diagnosed with RNET shows a significantly increasing incidence of RNET in younger adults. An age-specific comparative analysis showed a significantly greater increase in younger adults compared to older adults. A sex-specific analysis showed that the increase was mostly driven by younger women and by tumors diagnosed at an early stage. The age-specific difference in RNET incidence was noted in various races. A sensitivity analysis of microscopically confirmed RNET cases showed similar results to the overall analysis. Our study provides comprehensive epidemiological data aiming to guide further investigations on this emerging topic. Abstract Prior non-comparative data showed increasing incidence of rectal neuroendocrine tumors (RNET) in the US. We aimed to evaluate age-specific RNET incidence rates and time-trends in demographic- and tumor-specific populations. The RNET age-adjusted incidence rates were calculated from the United States Cancer Statistics (USCS) database between 2001 and 2020. The population was stratified by age into older (≥55 years) and younger adults (<55 years), as well as by sex and race. The tumors were categorized by their stage at diagnosis into early and late. The annual percentage change (APC) and average APC (AAPC) were estimated using joinpoint regression and Monte Carlo permutation analysis. Pairwise comparison assessed for parallelism and coincidence. There were 59,846 patients diagnosed with RNET between 2001 and 2020 (50.3% women). Overall, the RNET incidence rates during this period were increasing in younger but not older adults (AAPC = 3.12 vs. −1.10; AAPC difference = 4.22, p < 0.001), with non-identical non-parallel data (p-values < 0.001). While similar results were seen in men, a greater age-specific difference was noted in women (AAPC = 3.31 vs. −1.10; AAPC difference = 4.41, p = 0.003). The difference between younger and older adults was seen in non-Hispanic White (AAPC-difference = 4.89; p < 0.001) and non-Hispanic Black (AAPC-difference = 3.33; p = 0.03) patients, and, in most years, among Hispanic and Non-Hispanic Asian/Pacific Islander patients, and it was mostly driven by early-stage tumors (AAPC-difference = 3.93; p < 0.001). The nationwide data show a significantly increasing RNET incidence in younger adults, most notably in younger women and in early-stage tumors, seen in various races. Future studies should evaluate RNET risk factors and outcomes in demographic-specific populations.