Colon, colorectal, and all cancer incidence increase in the young due to appendix reclassification

BACKGROUND: Increases in colon and colorectal cancer incidence among adolescents and young adults have been reported progressively. Most of the increase may be because of an artifact caused by reclassifying appendiceal carcinoids and neuroendocrine tumor (NET) as malignant. METHODS: Age-adjusted incidence and survival data were obtained from the Surveillance, Epidemiology, and End Results SEER22 database. RESULTS: In adolescents and young adults during 2000-2020, appendix cancer had an average annual percent change in incidence increase that in males was 3.7 times greater than the next most increasing cancer (average annual percent change = 12.8, 95% confidence interval CI] = 10.9% to 14.6% vs average annual percent change = 3.4 kidney, 95% CI = 2.7% to 3.5%) and correspondingly in females 2.9-fold greater (average annual percent change = 14.6,95% CI = 11.9% to 17.3% vs average annual percent change = 4.2 pancreas, 95% CI = 3.6% to 4.8%). From 2000-2009 to 2015-2020, appendix cancer incidence increased 17-, 6.5-, and 2.5-fold in children aged 0-14 years, adolescents and young adults aged 15-39 years, and adults aged 40-49 years, respectively. NET accounted for 95%, 90%, and 80% of appendix cancer increase in the 3 age groups, respectively. In 3446 adolescents and young adults diagnosed during 2010-2020 with malignant appendix NET, the 6-year cancer-specific survival was 99.4% (95% CI = 99.0% to 99.6%). From 2000-2009 to 2015-2020, colon carcinoma incidence in adolescents and young adults increased 61% with the appendix included and only 11% with the appendix excluded. CONCLUSIONS: Reclassification of appendix NET/carcinoids as malignant has artifactually increased the incidence of colon, colorectum, and all cancer in children and adolescents and young adults. Appendix NET/carcinoids are rarely fatal in those aged younger than 40 years and should not be considered as cancer and included in colorectal cancer analyses. To the extent that the appendix artifact occurs in adults aged 40-49 years, recommendations for starting colorectal cancer screening earlier may be affected.