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

Abstract Introduction Increases in colon and colorectal cancer incidence among adolescents and young adults (AYAs) have been reported progressively. Most of the increase may be due to an artifact caused by reclassifying appendiceal carcinoids/neuroendocrine tumor (NET) as malignant. Methods Age-adjusted incidence and survival data were obtained from the Surveillance, Epidemiology, and End Results (SEER) SEER22 database. Results In AYAs during 2000-2020, appendix cancer had an average annual percent change (AAPC) in incidence increase that in males was 3.7 times greater than the next most increasing cancer (AAPC12.8,95%CI: 10.9-14.6 vs AAPC3.4 [kidney] , 95%CI : 2.7-3.5) and correspondingly in females 2.9-fold greater (AAPC14.6,95%CI : 11.9-17.3 vs AAPC4.2 [pancreas], 95%CI : 3.6-4.8). From 2000-2009 to 2015-2020, appendix cancer incidence increased 17-,6.5-and 2.5-fold in children 0-14, AYAs 15-39, and adults 40-49 years of age, respectively. Carcinoid/NET accounted for 95%, 90% and 80% of appendix cancer increase in the three age groups, respectively. In 3,446 AYAs diagnosed during 2010-2020 with ‘malignant’ appendix NET, the 6-year cancer specific survival was 99.4% (95%CI , 99.0%to99.6%). From 2000-2009 to 2015-2020, colon carcinoma incidence in AYAs 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 AYAs. Appendix NET/carcinoids are rarely fatal in < 40 year-olds and should not be considered as cancer and included in colorectal cancer analyses. To the extent that the appendix artifact occurs in 40-49 year-olds, recommendations for starting colorectal cancer screening earlier may be affected.\