Early-Onset Colorectal Cancer: Are Neuroendocrine Tumors or Adenocarcinomas the Culprit? Analysis of the Largest U.S. Cancer Incidence Database, 2001-2020.

(1) Background: While prior data showed an increasing incidence of colorectal cancer (CRC) in young adults, the contribution of adenocarcinoma (ADC) and neuroendocrine tumors (NETs) to this trend is not well studied. Therefore, we conducted a comparative analysis of the incidence rates and time trends of colorectal ADC and NETs in young adults (aged 24-54) using the United States Cancer Statistics (USCS) database. (2) Methods: Age-adjusted CRC incidence rates between 2001 and 2020 were calculated and categorized by sex, histopathology, and stage at diagnosis. Annual percentage change (APC) and average APC (AAPC) were computed via joinpoint regression utilizing weighted Bayesian information criteria to generate the simplest trend. Pairwise comparative analysis of ADC and NETs was conducted using tests of identicalness and parallelism. (3) Results: In this study, 514,875 patients were diagnosed with early-onset-CRC between 2001 and 2020 (54.8% men). While CRC incidence was significantly increased, including both ADC (448,670 patients) and NETs (36,205 patients), a significantly greater increase was seen for NETs (AAPC = 2.65) compared to ADC (AAPC = 0.91), with AAPC difference = 1.73 ( = 0.01) and non-identical non-parallel trends (-values < 0.001). This was most notable in males (AAPC difference = 1.81, = 0.03) and for early-stage tumors (AAPC difference = 3.56, < 0.001). (4) Conclusions: Our study, covering ~98% of the U.S. population provides the first comparative analysis of early-onset CRC histopathological subtypes, showing that the rate of increase of NETs in young adults is much greater than that of ADC. Given that patients with NETs with malignant behavior can experience significant mortality, our findings are importance, highlighting the rapidly increasing NET incidence in young adults and encouraging early screening that can improve outcomes.