Rising incidence of early-onset colorectal cancer: impact of anatomy and histology

This is the authors' abstract. We don't add key points for this paper.

The incidence of early-onset colorectal cancer (EO-CRC)—defined as CRC diagnosed in adults younger than age 50—has been steadily increasing over the past several decades. Although the steepest rise has been seen among adults aged 20-29 years, EO-CRC incidence is highest in adults aged 45-49 years, with an age-adjusted incidence rate of 33.4 per 100 000 between 2015 and 2019.1,2 EO-CRC is currently the leading cause of cancer-related death in men age <50 years and the second leading cause among women age <50 years.3,4 In response to these trends, the United States Preventative Services Task Force (USPSTF) formally recommended lowering the age at which to start CRC screening from 50 to 45 years for average-risk individuals in 2021.5 The target of these screening efforts is the early detection of colorectal adenocarcinomas, which are the most common histological subtype of colorectal tumors and associated with higher mortality than gastrointestinal neuroendocrine tumors (NET), which can also arise from the bowel but generally harbor more indolent biology. Gastrointestinal NETs, previously called carcinoid tumors, have also been noted to be increasing in incidence among younger adults. An analysis of the US Cancer Statistics database found that between 2001 and 2020, the overall incidence of gastrointestinal and pancreatic NETs in individuals age 15-55 years increased by an average of 5.23% per year.6 Anorectal NETs had the highest overall incidence rate among this group; however, appendiceal NETs had the steepest rise, increasing on average by 13.59% per year.6 Others have also noted a steep increase in appendix cancer incidence in individuals <50 years old.7,8 Notably, in an analysis of appendiceal cancer cases in SEER 18 from 2007-2016, NETs comprised 75.3% of appendiceal cancers in individuals age 20-39 years, but only ∼35% in individuals >50 years.8 The drivers of the rising rates of appendiceal NETs are not known. One proposed hypothesis is that the rise is artifactual, due to reclassification and recoding of NETs in large cancer registries.9,10 This has led to efforts to delineate epidemiological trends in both CRC and appendix cancer incidence by histological subtype.11-14