The development of colorectal cancer screening is a cancer control success. It is preventing thousands of deaths, but it has the potential of preventing thousands more. This can be achieved through offering all eligible patients high quality screening, diagnostics, and treatment. Let us educate and encourage colorectal screening among all average risk Americans beginning at 45. Let us not allow a recommendation to start at 45 to deemphasize screening those older persons who are most likely to benefit from colorectal cancer screening.

See related article by Liu et al., p. 1701

In this issue, Liu and colleagues provide important information regarding the prevalence of colorectal cancer screening in the U.S. population (1). Such information is helpful in determining where cancer control efforts should be targeted for the greatest impact. They document an increase in the prevalence of colorectal screening from 2000 to 2018. While the increase is seen across all races/ethnicities, all socioeconomic strata, and all ages 50 to 75, there are some of the expected disparities by race and socioeconomic status. In my opinion, an extremely important finding is 33.9% of Americans aged 50 to 75 are not up to date with colorectal cancer screening. This represents a significant opportunity to prevent deaths.

The period, 2000 to 2018 was a time when all major US colorectal screening recommendations suggested screening start at age 50. The authors note that National Health Interview Survey Data revealed that approximately 45.3% of adults aged 50 to 54 years reported recent screening in 2015. This was the lowest screening prevalence of any 5-year age group. They lament that Americans aged 45 to 49 will likely have the lowest screening prevalence with more recent guidance from the American Cancer Society and the US Preventive Services Task Force that screening start at 45. Their paper is a call for intensive efforts to encourage screening in people aged 45 to 49. Interestingly, they note “care must be taken to ensure screening benefits are realized equally by all population groups, particularly adults aged 45 to 49.”

I believe there should be public education efforts to promote screening beginning at age 45, but we should not stress screening in younger subjects at the expense of promotion of screening older subjects. Full disclosure, I was a co-author of the American Cancer Society screening guideline. I fully support colorectal screening of those at average risk beginning at age 45, but I cannot ignore the data indicating opportunity for substantial good if a larger proportion of Americans aged 50 to 75 were to participate in a program of routine screening (2).

The benefit of colorectal screening in persons aged 50 to 75 is not controversial. The University of Minnesota Colon Cancer Control Trial was a three-decade long prospective randomized trial. It demonstrated that stool guaiac testing with appropriate follow-up of positive tests reduces incidence of colorectal cancer by 20% and risk of colorectal cancer death by 33% (3, 4). Subsequent studies have shown that fecal immunochemical testing for hemoglobin, testing for certain stool DNA sequences, sigmoidoscopy, virtual colonoscopy, and optical colonoscopy combined with quality treatment reduce mortality in this age group (5).

Screening is most efficient in populations with substantial incidence of disease. Focusing on groups at high risk of diagnosis increases deaths averted per number screened. The vast majority of people who develop colorectal cancer are diagnosed in their late 60s. Age-adjusted incidence from 2013 to 2017 was 33.3 per 100,000 for Americans aged 45 to 49 and 118.3 per 100,000 for Americans 65 to 69. Incidence rates are affected by the prevalence of screening in the age group, but the higher rate among those 65 to 69 still suggests that the number needed to screen to avert one death is much lower among persons in their 60s versus person in the late 40s.

Efficiency of finding disease is an important point of consideration in areas where resources to support colonoscopy are inadequate. There are parts of the United States where the number of physicians capable of providing colonoscopy is limited. A recommendation of screening residents aged 45 and over will put more stress on the healthcare system in those areas. It could increase the difficulty of getting services for the highest risk and increase disparities by race, socioeconomic status, and age (6).

A substantial number of colorectal cancer deaths can be avoided if the 30% to 40% of Americans aged 50 to 75 not receiving routine screening were to get it. Liu and colleagues put great emphasis on the fact that preventing a colorectal death in a person aged 45 to 49 leads to more years of life saved. This is true for an individual, but the cumulative person years of lives lost from colorectal cancer among Americans (a population-based statistic) is far greater for older populations. Age at diagnosis is affected by screening intensity. Slightly less than 6% of Americans dying of colorectal cancer are diagnosed at age 45 to 49 and less than 8% are diagnosed age 50 to 54. This compares to 10% to 12% of those diagnosed in each of the age ranges 60 to 64, 65 to 69, and 70 to 75 (5).

It is important to discuss some of the factors that go into making the screening recommendation to start at age 45. There is minimal observational data suggesting and no prospective randomized trial result definitively showing that colorectal screening of persons age 45 to 49 reduces mortality. The guidelines rely heavily on extrapolation and modeling of data. The estimate or gamble is that the biologic behavior of colorectal cancer among people aged 45 to 49 is like that of older patients and the benefit of screening is similar, just five years earlier. It is especially defensible to accept these assumptions when one notes that risk of colorectal cancer diagnosis is similar for Americans aged 45 to 49, compared to those aged 50 to 54. Even the death rate among people diagnosed aged 45 to 49 is similar to those diagnosed aged 50–55 (7, 8).

The lack of a prospective clinical trial to address this issue specifically, is why the American Cancer Society gave screening in those aged 45 to 49 a “qualified recommendation.” The ACS gave regular screening in adults aged 50 and older a “strong recommendation (5).” Similarly, the US Preventive Services Task Force gave screening in those aged 45 to 49, a “B” recommendation and screening in those aged 70 to 75, an “A” recommendation (9).

The recommendation to begin routine screening at age 45 was motivated by a paradox in colorectal cancer mortality statistics (10). There has been a 50% decline in colorectal cancer death rates for Americans as a whole since 1980. There has been a small but significant rise in the colorectal cancer death rate for Americans under the age of 55.

The development of colorectal cancer screening is a cancer control success. It is preventing thousands of deaths. It has the potential of preventing thousands more. This can be achieved through offering all eligible patients high quality screening, diagnostics, and treatment. Let us educate and encourage colorectal screening among all average risk Americans beginning at 45. Let us not forget those older persons who are most likely to benefit from colorectal cancer screening.

O.W. Brawley reports personal fees from Grail outside the submitted work.

This work was supported by the NIH (P30 CA 0069783 and 1U10CA180820) and Bloomberg Philanthropies.

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