Researchers stress the importance of screening by histology, age

Over the past 20 years, the incidence of rectal carcinoid tumors has increased dramatically in younger patients, substantially impacting the incidence of overall colorectal cancer (CRC), according to results from a study published in Annals of Internal Medicine. Researchers stress that independent assessment of histologic CRC subtypes may help better understand the factors driving the overall incidence of CRC and guide efforts to reduce risks in appropriate patients.

“Recent studies using SEER (Surveillance, Epidemiology, and End Results) data demonstrated an increased incidence of early-onset colorectal cancer (EOCRC) since the 1980s. Although this increase is not fully understood, potential contributors include dietary factors, alcohol consumption, and rising obesity rates. The increase in EOCRC incidence contributed to a 2018 American Cancer Society recommendation to start CRC screening at age 45 instead of 50 years in persons at average risk,” wrote these researchers, led by Eric M. Montminy, MD, of Tulane University School of Medicine, New Orleans.

In their retrospective analysis, Montminy and colleagues used the SEER 18 databases from 2000-2016 to identify 119,624 patients with CRC. They determined the yearly incidence rates of age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology, adenocarcinoma, and carcinoid tumors, calculated per 100,000 population.

The greatest changes in adenocarcinoma 3-year average annual incidence rates occurred in the following groups:

  • Rectal-only CRC in individuals ages 20-29 years, which increased by 39% (0.33-0.46 per 100,000; P <0.050), with a corresponding annual percentage rate of 1.6% (P ˂ 0.050);
  • Rectal-only CRC in individuals ages 30-39 years, which increased by 39% (1.92-2.66 per 100,000; P < 0.50), with a corresponding annual percentage rate of 2.2% (P ˂ 0.050); and
  • Colon-only CRC in individuals ages 30-39 years, with an increase of 20% (3.30-3.97 per 100,000; P <0.050), with a corresponding annual percentage rate of 1.2% (P ˂ 0.050).

In individuals ages 40-49 years, the 3-year average annual incidence rates were increased for both colon-only (+13%; 12.21-13.85 per 100,000; P ˂ 0.050) and rectal-only (+16%; 7.50-8.72 per 100,000; P <0.050) subsites.

Colon-only carcinoid tumors were rare, but carcinoid tumors represented a large number of CRC and rectal cancer cases—approximately 4%-20% of all colorectal and 8%-34% of all rectal cases.

In all age groups—20-29, 30-39, 40-49, and 50-54 years—the incidence rates of colorectal carcinoid tumors increased more steeply than adenocarcinoma. These changes were greatest in those aged 50-54 years, who had a 159% (2.36-6.10 per 100,000) increase in rectal carcinoid tumors from 2000-2002 and 2014-2016, and an increase of 10% for adenocarcinoma (18.07-19.84 per 100,000). The combination of these represented a full 22.6% of all rectal cancer cases.

“Rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC [incidence rates] IRs. These findings underscore the importance of assessing histologic CRC subtypes independently. This approach may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research,” wrote Montminy and fellow researchers.

Although important, these results may not yet translate directly into the need to screen for CRC in younger patients, according to Michael Bretthauer, MD, PhD, of the University of Oslo, Oslo, Norway, and colleagues, in an accompanying editorial.

As way of background, they explained:

“In May 2018, the American Cancer Society (ACS) issued a new recommendation to start screening for colorectal cancer (CRC) at age 45 rather than 50 years in persons at average risk. That guideline increased the number of Americans eligible for screening by 22 million and prompted many questions about risks and benefits for patients as well as the consequences for providers and the health care system.”

But revising these recommendations may be deleterious to resource allocation for groups at highest risk, according to Bretthauer and fellow authors.

“The revised ACS guidance relied on analyses of the SEER (Surveillance, Epidemiology, and End Results) database highlighting a 22% relative increase in CRC incidence from 2000 to 2013 in persons aged 40 to 49 years (so-called early-onset CRC), from 5.9 to 7.2 cases per 100,000 person-years. Despite this increase, we and others were critical of the lower screening age because of the still very low absolute risk for CRC in persons younger than 50 years and the lack of empirical evidence for the efficacy of screening in this age group. The revised recommendation did not consider the societal cost of earlier screening, either in absolute expense or in the diversion of potentially limited resources away from populations with greater disease risk, in which screening would provide greater value,” they wrote.

Since carcinoid tumors are not the target of CRC screening, Bretthauer and colleagues urge caution in changing CRC screening recommendations.

“With the data reported in Annals and the inherent uncertainty of guidelines based on modeling, caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years. Scientific equipoise regarding the efficacy of CRC screening in young adults still exists. Equipoise situations in modern medicine call for clinical trials, not broad recommendations for implementation,” they concluded.

Study limitations include data collection beginning only in 2000 and the observational nature of the study.

  1. According to a recent population-based analysis, the greatest increases in the incidence of colorectal cancer (CRC) was seen in rectal adenocarcinomas in those aged 20-29 and 30-39 years.

  2. When analyzed according to histologic type, the greatest increases in CRC incidence were in colorectal carcinoid tumors in all age groups, a change largely driven by a significant increase in the incidence of rectal carcinoid tumors in those aged 50-54 years.

E.C. Meszaros, Contributing Writer, BreakingMED™

Montminy reported no conflicts of interest.

Bretthauer reports grants from Norwegian Research Council and the Norwegian Cancer Society for research in colorectal cancer screening.

Cat ID: 23

Topic ID: 78,23,16,23,192,925