Colorectal Cancer

Early detection is key

Colorectal cancer is the second-leading cause of cancer death in the United States, according to the U.S. Preventive Services Task Force. In 2016, when the USPSTF issued its most recent set of screening recommendations, an estimated 134,000 persons were likely to be diagnosed with the disease, and about 49,000 were expected to die from it.

Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 73 years.

The USPSTF found convincing evidence that screening for colorectal cancer in adults aged 50 to 75 years reduces colorectal cancer mortality. However, about one-third of eligible adults in the United States have never been screened for colorectal cancer. Offering choice in colorectal cancer screening strategies may increase screening uptake.

The benefit of early detection of and intervention for colorectal cancer declines after age 75 years, says USPSTF. Among older adults who have been previously screened for colorectal cancer, there is at best a moderate benefit to continuing screening during the ages of 76 to 85 years. However, adults in this age group who have never been screened for colorectal cancer are more likely to benefit than those who have been previously screened.

The time between detection and treatment of colorectal cancer and realization of a subsequent mortality benefit can be substantial. As such, the benefit of early detection of and intervention for colorectal cancer in adults 86 years and older is at most small.

Screening recommendations

In June 2016, the U.S. Preventive Services Task Force updated its recommendations regarding colorectal cancer screening. Eight years earlier, the USPSTF had recommended screening with colonoscopy every 10 years, annual FIT, annual high-sensitivity FOBT, or flexible sigmoidoscopy every five years combined with high-sensitivity FOBT every three years.

In the current recommendation (below), instead of emphasizing specific screening approaches, the USPSTF chose to highlight the convincing evidence that 1) colorectal cancer screening substantially reduces deaths from the disease among adults aged 50 to 75 years, and 2) not enough adults in the United States are using this effective preventive intervention.

Note that recommendations made by the U.S. Preventive Services Task Force are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Population	Recommendation	Grade
Adults aged 50 to 75 years	The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years.	A (There is a high certainty that the net benefit is substantial.)
Adults aged 76 to 85 years	The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history. · Adults in this age group who have never been screened for colorectal cancer are more likely to benefit. · Screening would be most appropriate among adults who 1) are healthy enough to undergo treatment if colorectal cancer is detected and 2) do not have comorbid conditions that would significantly limit their life expectancy.	C (The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.)

Population

Recommendation

Grade

Adults aged 50 to 75 years

The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years.

A (There is a high certainty that the net benefit is substantial.)

Adults aged 76 to 85 years

The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history.

· Adults in this age group who have never been screened for colorectal cancer are more likely to benefit.

· Screening would be most appropriate among adults who 1) are healthy enough to undergo treatment if colorectal cancer is detected and 2) do not have comorbid conditions that would significantly limit their life expectancy.

C (The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.)

Source: U.S. Preventive Services Task Force, June 2016 (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/colorectal-cancer-screening2#tab)

Colorectal cancer screening strategies

Table. Characteristics of Colorectal Cancer Screening Strategies^a

Screening Method	Frequency^b	Evidence of Efficacy	Other Considerations
Stool-Based Tests
gFOBT	Every year	High-sensitivity versions have superior test performance characteristics than older tests.	Does not require bowel preparation, anesthesia, or transportation to and from the screening examination (test is performed at home)
FIT^c	Every year	Improved accuracy compared with gFOBT. Can be done with a single specimen	Does not require bowel preparation, anesthesia, or transportation to and from the screening examination (test is performed at home)
FIT-DNA	Every 1 or 3 years^d	Specificity is lower than for FIT, resulting in more false-positive results, more diagnostic colonoscopies, and more associated adverse events per screening test. Improved sensitivity compared with FIT per single screening test	There is insufficient evidence about appropriate longitudinal follow-up of abnormal findings after a negative diagnostic colonoscopy; may potentially lead to overly intensive surveillance due to provider and patient concerns over the genetic component of the test.
Direct Visualization Tests
Colonoscopy^c	Every 10 years		Requires less frequent screening. Screening and diagnostic followup of positive results can be performed during the same examination.
CT colonography^e	Every 5 years		There is insufficient evidence about the potential harms of associated extracolonic findings, which are common
Flexible sigmoidoscopy	Every 5 years	Modeling suggests it provides less benefit than when combined with FIT or compared with other strategies	Test availability has declined in the United States
Flexible sigmoidoscopy with FIT^c	Flexible sigmoidoscopy every 10 years plus FIT every year		Test availability has declined in the United States. Potentially attractive option for patients who want endoscopic screening but want to limit exposure to colonoscopy.

Abbreviations:FIT=fecal immunochemical test; FIT-DNA=multitargeted stool DNA test; gFOBT=guaiac-based fecal occult blood test.

Source: U.S. Preventive Services Task Force, June 2016 (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/colorectal-cancer-screening2#tab)

What’s ahead for FIT?

Testing for novel protein biomarkers in stool finds significantly more colorectal cancers (CRC) and advanced adenomas (precursors to cancer) compared to testing for hemoglobin alone, according to researchers from the Netherlands Cancer Institute and VU University Medical Center, and published in Annals of Internal Medicine in November 2017.

The proteins can be detected in a small sample of the fecal immunochemical test (FIT), which suggests that they can be applied in population screening.

The researchers sought to identify novel protein biomarkers in stool that could outperform or complement hemoglobin in detecting CRC and advanced adenomas. They used mass spectrometry to search for proteins that were present in stool specimens from persons with CRC or advanced adenomas, and which were virtually absent from stool specimens from controls. By using a combination of four novel protein biomarkers, in this study the investigators found that they were able to detect almost twice as many colorectal cancers and five times as many advanced adenomas, compared to using hemoglobin alone.

According to the researchers, this new test has the potential to be easily integrated into population-wide screening programs upon successful clinical validation. Because it uses the same technology as the current standard stool-based test, few adjustments to the screening program would be needed.