From the Journals

CRC risk in young adults: Not as high as previously reported

Implications for CRC screening.


The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia – call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out.

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.


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