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CRC Incidence Among Younger US Adults Continues to Rise
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Colorectal cancer diagnoses among individuals aged younger than 50 years continued to increase in the United States over the past decade, according to results of a retrospective study published in Cancer.
The increased incidence — plus the fact younger adults more often present with and die of advanced disease — should be factored into conversations about colorectal cancer screening guidelines, researchers concluded.
“Several studies over the last few years have shown that the incidence rates and the mortality of colorectal cancer [among] younger adults have increased in the U.S. over the past 30 years,” Boone Goodgame, MD, medical director of Shivers Cancer Center, medical director for oncology at Seton Healthcare Family and assistant professor of medicine at The University of Texas at Austin, told HemOnc Today. “We were able to confirm these trends in a larger database that captures the majority of patients in the U.S. with cancer. We showed that this trend has particularly worsened in the last decade.”
Overall incidence of colorectal cancer incidence has decreased in the United States over the past several decades, but SEER data have shown incidence is increasing among individuals aged younger than 50 years.
Last year, the American Cancer Society updated its guidelines to recommend that adults at average risk for colorectal cancer begin screening at age 45 years. However, the U.S. Preventive Services Task Force continues to recommend screening for asymptomatic adults be performed between ages 50 and 75 years.
Virostko and colleagues conducted their study to determine whether the National Cancer Database (NCDB) — which includes more than 70% of new cancer cases in the U.S. — mirrored the trend of earlier colorectal cancer incidence observed in the SEER database, which accounts for 28% of the U.S. population.
The analysis included 1.18 million people diagnosed with colorectal cancer between 2004 and 2015. Of these, 11% (n = 130,165) were diagnosed prior to age 50 years, and 89% (n = 1.05 million) were diagnosed at age 50 years or older.
The percentage of colorectal cancer cases diagnosed among adults aged younger than 50 years increased from 10% in 2004 to 12.2% in 2015 (P < .0001).
Those aged younger than 50 years appeared more likely than those aged 50 years or older to have primary rectal tumors (40% vs. 28.5%; P < .0001). They also were more likely to have stage III disease (28.1% vs. 23.1%; P < .0001) or stage IV disease (23.5% vs. 16.9%; P < .0001).
Younger adults had higher rates of lymph node involvement and metastatic disease. However, the 90-day mortality rate was higher among older patients.
When researchers analyzed colorectal cancer cases among both men and women, results showed an increasing proportion of cases diagnosed at a young age among non-Hispanic whites (P < .001) and Hispanic whites (P < .05) but not among blacks or Asians.
Investigators then stratified ethnic and racial groups by sex. Among men, they only observed a proportional increase in diagnosis prior to age 50 years among non-Hispanic whites (P < .0001). Among women, they observed proportional increases among non-Hispanic whites (P < .001) and Hispanic whites (P < .05).
“I was surprised that — [among] African Americans and Hispanics with colon cancer — 14% and 18.3% respectively were diagnosed before age 50, and this did not change over the decade we studied,” Goodgame said. “The increase in younger cases was predominantly seen [among] persons of white race in nonrural areas, which is difficult to explain.”
The researchers acknowledged study limitations. Unlike the SEER database, the National Cancer Database does not collect population data. Consequently, it cannot calculate incidence or other epidemiologic metrics. In addition, patients with lower socioeconomic status are less likely to be treated at accredited cancer centers represented in the database.
Large prospective studies of individuals aged younger than 50 years “are strongly needed” to help identify those at greatest risk for colorectal cancer, and to provide more insights into the potential benefits, risks and costs of screening for that population, Goodgame and colleagues wrote.
“Cancer is still predominantly a disease of older people and, for this reason, it is frequently missed or diagnosed late in younger people,” Goodgame told HemOnc Today. “[Because] these rates are increasing, physicians and patients need to be more aware of potential cancer symptoms and more vigilant in adhering to screening guidelines.”
Although an increase in diagnoses among any population is concerning, the magnitude of the increase among individuals aged younger than 50 years is small, and colorectal cancers in this age group remain rare, Chyke A. Doubeni, MD, MPH, a USPSTF member who serves as presidential professor and associate professor of epidemiology at University of Pennsylvania, wrote in an accompanying editorial.
Doubeni reiterated the concerns about the NCDB’s limitations.
Because it is not population based, it cannot provide incidence or mortality rates, he wrote. Also, the NCDB may not adequately capture data from individuals from disadvantaged backgrounds, and it captures a greater proportion of younger patients than those aged 65 years or older.
“Because of these limitations, NCDB data are not suited for informing trends in cancer incidence or subgroups disproportionately affected,” Doubeni wrote.
The impact of expanded screening to younger individuals also remains unclear, he added.
“Because the number of colorectal cancer cases from inherited causes is much higher in younger individuals, it is unknown whether screening for sporadic cases in a group with such low disease rates would result in a favorable balance of harms and benefits,” Doubeni wrote. “It is, therefore, imperative that the various hypotheses for increasing colorectal cancer incidence among people younger than 50 years be rigorously tested to determine whether changing the current screening age for people who are not at increased familial risk represents the most appropriate public health response.” – by John DeRosier
Disclosures: The authors report no relevant financial disclosures. Doubeni reports membership on the USPSTF, as well as an author role with UpToDate.
Perspective
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Jordan J. Karlitz, MD
This is an important study because of the debate over whether colorectal cancer screening should begin at age 45 or 50. This study adds a new perspective on the colorectal cancer burden in people younger than 50. The authors took a different approach where they looked at the proportion of cases diagnosed younger than 50 vs. age 50 and older and how those have changed over time. They used the National Cancer Database (NCDB) from 2004-2015 and found that the proportion of the total number of patients diagnosed with colorectal cancer aged younger than 50 rose during the study period (10% in 2004 vs. 12.2% in 2015). Younger patients presented with more advanced disease. Although the proportion of earlier diagnosis rose in all income quartiles, they found that the highest income quartile had the highest proportion of younger cases. The proportion also rose in urban, but not rural, areas. The authors also found that in men, only non-Hispanic white individuals showed an increase in the proportion of cases diagnosed aged younger than 50; whereas in women, non-Hispanic white individuals and Hispanic white individuals had increase in this proportion.
The use of proportions in this study contrasts with prior studies demonstrating rising colorectal cancer incidence rates in younger patients in which incidence rates per 100,000 were used. The reason that proportions were used is that the NCDB collects only absolute numbers of cases and is not matched to local populations, so incidence rates cannot be measured.
A strength of using the NCDB is, according to the authors, it represents more than 70% of newly diagnosed cancer cases in the U.S. However, there are a number of limitations to consider when interpreting this study. Importantly, and as mentioned by the authors, the use of relative proportions before age 50 vs. age 50 and older means that “the relative increase in young cases found in this study likely reflects both the true rising incidence in young patients and the decreasing incidence of CRC in older patients.” Further limitation is that patients with lower socioeconomic status may be less likely captured within the NCDB. Hence, the results, including the subgroup analyses described above must be interpreted with caution. Nevertheless, the results are thought-provoking and, combined with preexisting studies, create further impetus for additional studies to home in on the etiology of early-onset CRC development. I have been fortunate to be involved in a Fight Colorectal Cancer Working Group. A number of us met in Denver in February 2019 to explore research priorities regarding early-onset CRC.
I think a key take home message is that at this time, although the etiology of rising early-onset CRC may not be completely known, we have to diligently assess younger patients with concerning symptoms to assure that they are evaluated in an expeditious manner. For example, for young patients with rectal bleeding, we cannot assume that this is benign in nature (eg, due to hemorrhoids); they should be referred for further work up, including colonoscopy. Further, as providers, we have to be diligent about taking detailed family histories to try to identify higher-risk patients for earlier screening. We also need to be mindful, that it is not just a family history of colorectal cancer that places younger patients at higher-risk, but also other types of cancers, often outside of the GI tract, that could indicate the presence of a familial syndrome, such as Lynch syndrome. Additionally, even a family history of an advanced adenoma (not yet colorectal cancer), may prompt earlier screening in family members. This is a point that is highlighted in the USMSTF guidelines that providers should be familiar with and also something that our working group at the National Colorectal Cancer Roundtable has been focusing on (including the development of a toolkit).
Overall, studies like this are important to help inform decision making in guidelines. Not all the guidelines align, in terms of whether average-risk screening should begin at age 45 or 50. The American Cancer Society recently came out stating that all average-risk individuals should begin screening at age 45, whereas some of the other guidelines continue to say 50, although the USMSTF recommends age 45 in African Americans.
Such studies make it possible to further interpret data so there can be critical evaluation of the guidelines.
References:
- Dwyer AJ. Gastroenterology. 2019;doi:10.1053/j.gastro.2019.04.049.
- Rex DK. Am J Gastroenterol. 2017;doi:10.1038/ajg.2017.174.
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