Colorectal cancer in the 45-to-50 age group in the United States: a National Cancer Database (NCDB) analysis

From 2004 through 2017, there were 67,442 cases of colorectal adenocarcinoma in patients 45 to 50 years old. Of these, 54% (n = 36,417) were male and 46% (n = 31,025) female. The majority were white (78.3%, (n = 52,827). The most frequent site was the colon (59.7%, n = 40,247), followed by rectum (30%, n = 20,219) and then the rectosigmoid junction (10.3%, n = 6,976). From the surgical pathology, 26.5% (n = 17,862) had stage III and 21.1% (n = 14,200) had stage IV disease. Full demographic and pathologic data are in Table 1.

This work quantified the growth of CRC in the 45-to-50 population, finding an AAPC of 1.6% from 2004 through 2017. Without any changes, the incidence rates for CRC in the 45-to-50 population would increase 25% in a 13-year period, from 2017 to 2030. Additionally, sex, race, and anatomic site-specific variations in incidence were found within the 45-to-50 group. The greatest CRC increases were in American Indian/ Alaska Natives/ and Asian American/ Pacific Islander races, rectal cancer, and male sex.

This work uniquely quantifies the impact of CRC in the 45–50-year-old population, which has the potential change trends in the burden of CRC from the recent change in screening guidelines. The premature morbidity and mortality in this working age have major impact on the nation’s labor productivity, as this age contributes the greatest participation rates and productivity to the US work force [18]. Nearly half of the 45-to-50-year-old CRC cases presented with advanced stage disease, stage III or IV. These cases bear an inherently worse prognosis and subsequently a greater burden for this cohort [19‐22]. Prior studies in other countries reported a substantial contribution from CRC premature mortality to earning losses. In Spain, the losses amounted to up to 10% or €510 million, of all cancer-related productivity losses in. In Ireland, these losses are estimated to accumulate to €8.3 billion between 2011 and 2030. Worldwide in 2017, CRC caused 19 million DALY, of which 95% were YLL [1, 23‐25]. This is aligned with our findings of an impactful CRC burden of 899,905 DALY and massive lost earnings, resulting almost entirely from YLL. In an economic evaluation in the US, Bradley et al. assessed the cost savings from CRC screening in the overall population by 2020 could result in 101,353 deaths avoided and $33.9 billion in savings in reduced productivity loss, $12.4 billion from risk factor reduction, and $8.4 billion from improved treatment [26]. Thus, there is great potential benefit for the individuals and society in lowering the CRC screening age to 45 years old and targeting this population to ensure compliance.

The recently published USPSTF guidelines stated that there would be a moderate benefit in reducing CRC mortality and increasing life years gained in lowering the screening recommendation from 50 to 45 [8, 9]. Some evidence used by the USPSTF stems from a microsimulation model, where the benefits from lowering the initial screening age to 45 resulted in a moderate increase in life years gained and decrease in CRC cases and mortality, outweighing the estimated burden from screening [27]. They provided estimations for the general population at average risk, while the current work uses a retrospective review of actual hospital-based data. The findings in the current work agree and complement this modeling. We found missed opportunities for earlier diagnosis in almost half of the cohort. CRC is preventable and amenable to treatment if detected early and appropriate treatment delivered [28, 29]. Previous work has shown younger patients are more tolerant and more likely to receive appropriate treatment [30‐32]. Thus, there is great potential benefits for the 45-to-50 cohort specifically from lowering the CRC screening recommendations.

The increase in CRC rates over time in individuals from 45-to-50 years old contrasts with the overall population trends. According to CRC statistics work in United States, the overall CRC rates have been declining since the mid-1980s, related to change in risk factors and CRC screening uptake. While the incidence rates for individuals 50 years old and younger had been increasing since the mid-1990s [10]. The current CRC 5-year AAPC for overall male population is − 1.5% and for female is − 1.0% [4].

The overall increase in EOCRC has been reported by other works.[2, 4, 33] This work is the 1^st to focus just on the 45–50-year-old population having an active intervention. Several published works in the overall EOCRC population agree with the findings here of higher incidence for males and certain racial minorities, but within all EOCRC ages.[10, 34] Published works also differ from the current work in demographic and anatomic variations. Siegel et al. reported EOCRC (20–49 years old) increased in young adults, with a ten-year AAPC from 0.8% to 4.2% (2.2% in United States) and no anatomic site-specific variation [2]. In New York State, Altieri et al. reported an increase in CRC for patients 21–50 years old, but with no association to race or gender [35]. Regardless of any heterogeneity in findings across studies, the common denominators driving the disparities in CRC trends are known risk factors and socio-economic factors. Alcohol consumption, smoking, obesity, sedentary lifestyle, and high-fat, processed diets, [36, 37] as well as access to convenient cost-effective, high-quality screening affect CRC trends [38]. Race is another factor impacting trends. In this work, there was an alarming increase in CRC rates in other patients in the 45-to-50 age group. Some racial disparities in CRC trends might be related to unmodifiable genetic factors. But race is also a social construct, grouped by differences in income, education, health insurance, and access to care and screening. The effectiveness of the screening recommendations could be lower in this population, and targeted interventions may enhance access and improve earlier-stage detection in the most vulnerable populations [10]. For instance, recognizing that African Americans were being diagnosed at a younger average with more advanced stage disease and had the highest CRC mortality, the American College of Gastroenterology (ACG) changed guidelines to recommend that African Americans should begin their CRC screening at age 45 [39]. While screening disparities still exist, CRC screening rates among African Americans have improved significantly since changing the initial guidelines. Programs that target individuals, their communities, address known barriers to screening, use multiple methods of message delivery, and are delivered over multiple time points in addition to earlier screening may have the best outcomes for reversing the trends seen within the 45-to-50 population [40, 41].

Although this work’s estimations comprehend a 13-year time frame, it is unlikely that the CRC rates in the 45-to-50-year-old population would decline or even reach a plateau, beyond this period, without any interventions. The largest population groups are the 20–39 years old, currently [42]. Considering the reported positive trends in CRC in this age bracket and this being the most populous group [4], we would expect to see rates continue to rise exponentially for the foreseeable future.

We recognize the limitations in the current work. The NCDB-PUF is a retrospective hospital-based registry, so there are limitations in the data fields available, risks for data entry errors, and assumptions made from the fields reported. However, the NCDB-PUF is a nationally representative, large sample with quality standards in data collection and reporting to maintain accreditation and systematically employed quality checks [12, 43]. These features yield a reliable and comprehensive hospital registry that can be used for cancer trend studies. Additional compensations as health insurance, retirement benefits, and paid leaves are not factored in the loss of future earnings calculation, what might result in underestimation. The possible benefits are also reliant on eligible patients having the appropriate screening. With the current rates of compliance with screening less than 2/3 in the general population, further work will need to assess effective screening uptake strategies.

In conclusion, CRC has been steadily increasing in the US in the 45-to-50 age group at an AAPC of 1.6%. Without any intervention, the incidence will continue to rise 25% through 2030. There is a huge economic and quality of life burden from CRC in this population. Thus, there is great potential benefit in lowering the recommended routine CRC screening age to 45. Higher rates of CRC incidence were seen within the 45-to-50 age group for male and AI/AN-API races. These disparities can guide targeted interventions to optimize the uptake of screening in these groups. In benchmarking the current and potential future CRC burden in this group, ongoing research can be designed to assess outcomes on the US incidence and survivorship from this change in screening guidelines. Additionally, this assessment could be useful in other countries as well. Having data are imperative for making evidence-based decisions for public health initiative. Even when national screening programs are in place, performing this exercise is important to ensure that the population is compliant and the methods selected for screening are effective.