Contributions of Adenocarcinoma and Carcinoid Tumors to Early-Onset Colorectal Cancer Incidence Rates in the United States.

BACKGROUND: Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as "colorectal cancer" in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported. OBJECTIVE: To assess EOCRC IRs and changes in IRs over time, stratified by histology. DESIGN: Retrospective analysis. SETTING: Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology ("overall" CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age. PATIENTS: 119 624 patients with CRC. MEASUREMENTS: IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years. RESULTS: The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000]; P < 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000]; P < 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000]; P < 0.050). Corresponding APCs were 1.6% (P < 0.050), 2.2% (P < 0.050), and 1.2% (P < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000]; P < 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000]; P < 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases. LIMITATION: Population-based data. CONCLUSION: These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research. PRIMARY FUNDING SOURCE: None.

Geographic and intra-racial disparities in early-onset colorectal cancer in the SEER 18 registries of the United States.

BACKGROUND: Although early-onset colorectal cancer (EOCRC) incidence rates (IRs) are increasing, geographic and intra-racial IR disparities are not well defined. METHODS: 2000-2015 Surveillance, Epidemiology, and End Results (SEER) program CRC IR Analysis (170,434 cases) was performed from ages 30 to 60 in four US regions, 18 individual registries, metropolitan and nonmetropolitan locations and stratified by race. Analyses were conducted in 1-year and 5-year age increments. RESULTS: Wide US regional EOCRC IR variations exist: For example, age 45 IRs in the south are 26.8/100,000, 36.0% higher than the West, 19.7/100,000 (p < 0.0001). Disparities magnify between individual registries: EOCRC IRs in highest risk registries were 177-348% (Alaska Natives), 75-200% (Hawaii), 76-128% (Louisiana), and 61-125% (Kentucky) higher than lowest risk registries depending on age. EOCRC IRs are 18.2%-25.6% higher in nonmetropolitan versus metropolitan settings. Wide geographic intra-racial disparities exist. Within the White population, the greatest IR difference (78.8%) was between Kentucky (5.9/100,000) and Los Angeles (3.3/100,000) in 30- to 34-year-olds (p < .0001). Within the Black population, the greatest difference (136.2%) was between rural Georgia (30.7/100,000) and California excluding San Francisco-Oakland/San Jose-Monterey/Los Angeles (13/100,000) in 40- to 44-year-olds (p = 0003). CONCLUSION: Marked geographic EOCRC disparities exist with disproportionately high IRs in Alaska Natives, Hawaii, and southern registries. Geographic intra-racial disparities are present within White and Black populations. In Blacks, there are disproportionately high EOCRC IRs in rural Georgia. Although vigilance is required in all populations, attention must be paid to these higher risk populations. Potential interventions include assuring early investigation of symptoms, targeting modifiable risk factors and utilizing earlier age 45 screening options supported by some guidelines.

Trends in Incidence of Early-Onset Colorectal Cancer in the United States Among Those Approaching Screening Age.

Importance: Early-onset colorectal cancer incidence rates among patients aged 45 to 49 years have been considered much lower compared with the rates among patients aged 50 to 54 years, prompting debate about earlier screening benefits at 45 years. However, the observed incidence rates in the Surveillance, Epidemiology, and End Results (SEER) registries may underestimate colorectal cancer case burdens in those younger than 50 years compared with those older than 50 years because average-risk screening is generally not performed to detect preclinical cases of colorectal cancer. Finding steep incidence increases of invasive stage (beyond in situ) cases of colorectal cancer from age 49 to 50 years would be consistent with high rates of preexisting, undetected cancers in younger patients ultimately receiving a diagnosis of colorectal cancer after undergoing screening at 50 years. Objective: To assess the preclinical burden of colorectal cancer by analyzing its incidence in 1-year age increments, focusing on the transition between ages 49 and 50 years. Design, Setting, and Participants: Data from the SEER 18 registries, representing 28% of the US population, were used to conduct a cross-sectional study of colorectal cancer incidence rates from January 1, 2000, to December 31, 2015, in 1-year age increments (ages 30-60 years) stratified by US region (South, West, Northeast, and Midwest), sex, race, disease stage, and tumor location. Statistical analysis was conducted from November 1, 2018, to December 15, 2019. Main Outcomes and Measures: Incidence rates of colorectal cancer. Results: A total of 170 434 cases of colorectal cancer were analyzed among 165 160 patients (92 247 men [55.9%]; mean [SD] age, 51.6 [6.7] years). Steep increases in the incidence of colorectal cancer in the SEER 18 registries were found from 49 to 50 years of age (46.1% increase: 34.9 [95% CI, 34.1-35.8] to 51.0 [95% CI, 50.0-52.1] per 100 000 population). Steep rate increases from 49 to 50 years of age were also seen in all US regions, men and women, white and black populations, and in colon and rectal cancers. The rate ratio incidence increase in the SEER 18 registries from 49 to 50 years of age (1.46 [95% CI, 1.43-1.51]) was significantly higher than earlier 1-year age transitions. Steep rate increases in the SEER 18 registries were found from 49 to 50 years of age in localized-stage (75.9% increase: 11.2 [95% CI, 10.7-11.7] to 19.7 [95% CI, 19.0-20.3] per 100 000) and regional-stage (30.3% increase: 13.2 [95% CI, 12.7-13.8] to 17.2 [95% CI, 16.7-17.8] per 100 000) colorectal cancers. A total of 8799 of the 9474 cases (92.9%) of colorectal cancer in the SEER 18 registries from 2000 to 2015 that were diagnosed among individuals aged 50 years were invasive. Conclusions and Relevance: Steep incidence increases between 49 and 50 years of age are consistent with previously undetected colorectal cancers diagnosed via screening uptake at 50 years. These cancers are not reflected in observed rates of colorectal cancer in the SEER registries among individuals younger than 50 years. Hence, using observed incidence rates from 45 to 49 years of age alone to assess potential outcomes of earlier screening may underestimate cancer prevention benefits.