Colorectal cancer screening: new recs from USPSTF

 The US Preventive Services Task Force just released their new colorectal cancer screening guidelines for asymptomatic adults at an average risk of colorectal cancer, in particular lowering the age recommended to 45; average risk = no prior diagnosis of colorectal cancer, adenomatous polyps, or inflammatory bowel disease, and no personal diagnosis of family history of known genetic disorders that predispose adults to high lifetime risk of colorectal disease (e.g. Lynch syndrome or familial adenomatous polyposis): see https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening or https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening#fullrecommendationstart

 

Recommendations: 

-- adults age 50-75: screening recommended for all adults (grade A recommendation)

-- adults aged 45-50: screening recommended (grade B recommendation)

-- adults age 76-85: selective screening recommended; evidence suggests the net benefit in this group is small, and clinicians should consider the patient's overall health, prior screening history, and preferences (grade C recommendation)

 

-- recommended screening methods (no order of priority):

    -- high-sensitivity guaiac fecal occult blood test (HSgFOBT) or FIT test screen every year

    -- stool DNA-FIT every 1 to 3 years

    -- CT colonography every 5 years

    -- flexible sigmoidoscopy every 5 years

    -- flexible sigmoidoscopy every 10 years along with annual FIT

    -- colonoscopy every 10 years

 

-- for adults 45-49yo: adequate evidence for testing that stool test, colonoscopy, CT colonography, or flexible sigmoidoscopy are the basis for their conclusion of a moderate benefit in reducing colorectal cancer mortality and increasing life-years gained, noting that earlier screenings by modeling analysis are associated with fewer colorectal cancer deaths in this younger age group. And the harms of screening are quite small

 

-- for older adults aged 76-85: routine screening by stool test, colonoscopy, CT colonography, or flexible sigmoidoscopy should provide only a small to moderate benefit in reducing colorectal cancer mortality and increasing life-years gained; the harms are small to moderate, largely from colonoscopy (for screening, or for follow-up of a positive finding from another test)

 

Commentary: 

-- colorectal cancer is the 3rd leading cause of cancer death in both men and women in the US, with a projected annual mortality of about 53,000 people in 2021

-- though the most frequent group with the diagnosis of colorectal cancer is in those 65-74 years old, its incidence is increasing in younger people

    -- 10.5% of new diagnoses occur in people younger than 50yo

    -- colorectal adenocarcinomas in those age 40-49yo increased by 15% from 2000-2002 to 2014-2016

    -- relative incidence by age:

        -- age 40-49: 20.0 new colorectal cancer cases/100,000 persons

        -- age 50-59: 47.8 new cases/100,000 persons

        -- age 60-69: 105.2 new cases/100,000 persons

-- the new recommendations reinforce their prior recommendation that screening those 50-75 has a high degree of certainty for substantial net benefit; but now recommends that screening those age 45-49 has moderate certainty of a moderate net benefit

-- people aged 76-85 who have been previously screened have a small net benefit (with moderate certainty), though those who never been screened are more likely to benefit

 

-- one issue they dealt with was whether there should be a differential approach based on certain groups: the colorectal cancer rates are higher in Black adults and American Indian/Alaskan Native adults, and in persons with a family history of colorectal cancer, men, and persons with other risk factors (e.g. obesity, diabetes, long-term smoking, unhealthy alcohol use)

    -- Black adults have 43.6 cases of colorectal cancer/100,000 persons, American Indian/Alaskan Native adults 39.0 cases/100,000 persons, white adults 37.8 cases/100,000 persons, Latinx 33.7 cases/100,000 persons and Asian/Pacific Islanders 31.8 cases/100,000 persons.

        -- The causes for these disparities, per their document, are complex and evidence points to inequities in access and utilization and the quality of colorectal cancer screening and treatment as the primary drivers for these health disparities, and not genetic differences

        -- USPSTF encourages clinicians to ensure Black persons receive recommended colorectal cancer screening, follow-up, and treatment; and that systems of care be developed to ensure all get high quality access across the continuum of screening and treatment

 

-- FIT testing: there is the standard annual FIT test, which uses antibodies to detect blood; there is also the stool DNA test that includes a FIT component (sDNA-FIT), which leads to more colonoscopies, and, based on modeling studies, they recommend every 1 to 3 years for the latter

-- for the direct visualization tests they note that colonoscopy every 10 years or CT colonography every 5 years have greater estimated life-years gained than flexible sigmoidoscopy every 5 years

-- accuracy of screening test, with colonoscopy being the gold standard:

    -- high-sensitivity gFOBT:

        -- for colorectal cancer: sensitivity ranges from 0.50-0.75 (0.09-1.0), specificity from 0.96-0.98 (0.95-0.99)

        -- for advanced adenomas: sensitivity 0.06-0.17 (0.02-0.23), specificity 0.96-0.99 (0.96-0.99)

    -- FIT:

        -- for colorectal cancer: pooled sensitivity 0.74 (0.64 -0.83), specificity 0.94 (0.93-0.96)

        -- for advanced adenomas: sensitivity 0.06-0.17 (0.02-0.23), specificity 0.96 (0.95-0.97)

    -- sDNA-FIT:

        -- for colorectal cancer: pooled sensitivity 0.93 (0.87-1.0), specificity 0.84 (0.84-0.86)

        -- for advanced adenomas: sensitivity 0.43 (0.40-0.46), specificity 0.89 (0.86-0.92)

    -- colonoscopy (with accuracy as determined by missed cases of colorectal cancer by follow-up CT colonography or repeated colonoscopy for discrepant findings on CT colonography)

        -- for colorectal cancer: not reported

        -- for advanced adenomas measuring at least 10 mm: sensitivity ranged from 0.89 (0.78-0.96) to 0.95 (0.74-0.99), specificity (from a single study) was 0.89 (0.86-0.91)

    -- CT colonography:

        -- colorectal cancer: sensitivity ranged from 0.86-1.0 (0.21-1.0), specificity not reported

        -- adenomas measuring at least 10 mm: sensitivity 0.89 (0.83-0.96), specificity 0.94 (0.89-1.0)

-- benefits of early detection and treatment:

    -- flexible sigs have a significant decrease in colorectal cancer mortality of 36% over 11 to 17 years of follow-up, mortality rate ratio 0.74 (0.68-0.80)

        -- most studies reviewed only a single round of screening

        -- there was an interesting observational study in the UK that found that a single flexible sigmoidoscopy screening significantly reduced subsequent colorectal cancer incidence over 17 years by 26% and colorectal cancer mortality by 30% (see http://gmodestmedblogs.blogspot.com/2017/04/one-time-flex-sig.html ), sigmoidoscopy having the advantage of being less invasive than colonoscopy, not requiring the intensity of the bowel prep, having less morbidity than colonoscopy, and (obviously) only picking up left-sided cancers (though the benefit of picking up right-sided cancers is significantly less clear, as noted in this blog)

    -- colonoscopy (from cohort studies) those receiving at least one colonoscopy had a 68% decrease colorectal mortality, adjusted hazard ratio of 0.32 (0.24-0.45)

        -- another Medicare study found similar numbers with a 58% decrease colorectal mortality

    -- FIT testing: 3 rounds of biennial FIT testing had a 10% decreased risk of colorectal cancer mortality at 6 years, adjusted relative risk of 0.90 (0.84-0.95)

 

-- harms of screening and treatment: mostly from false positive and false negative results, and from the harms of the workup of positive screening results with colonoscopy

    -- serious harms from colonoscopy are estimated to be 17.5 serious bleeding events and 5.4 perforations per 10,000 colonoscopies

-- harms from flexible sigmoidoscopies were 0.5 bleeding events and 0.2 perforations per 10,000 sigmoidoscopies

-- harms from CT colonography are mostly related to incidental extra-colonic findings on CT leading to medical or surgical treatments. Radiation involved is 0.8 to 5.3 mSv (for reference: annual background radiation dose is 3.0 mSv)

 

comparison to other guidelines:

-- several included lowering the screening age to 45 in Black adults; and at age 40 or 10 years before the age of diagnosis of a family member in those with a family history of colorectal cancer (e.g. see the US Multi-society Task Force recommendations: http://gmodestmedblogs.blogspot.com/2017/07/new-colon-cancer-screening-guidelines.html )

    -- this guideline also tiered their recommendations so that colonoscopy every 10 years or annual FIT tests were the preferred screening tests

    -- they also dismiss the FIT-DNA tests because of its decrease in specificity and high cost

-- the new guidelines from the American College of Physicians suggested screening ages 50-75, with a clear stop age at 75 or for those with life expectancy 10 years or less. They suggested FIT testing every 2 years (as is also recommended in Canada): seehttp://gmodestmedblogs.blogspot.com/2019/11/colon-ca-screening-per-acp.html

 

Limitations:

-- there are only cohort studies looking at colonoscopy and FIT testing, and NO randomized controlled trials. The cohort studies however are pretty impressive and lead to the high recommendation for these tests

-- colonoscopy, as noted above, does not have a great sensitivity or specificity even for lesions >10mm, which may undercut the results above for the other tests (ie, this "gold standard" seems to have some pyrite, or fool's gold, mixed in)

-- there also need to be head-to-head comparison studies in order to accurately tier screening tests against each other

    -- the current guidelines are comparing studies of individual tests to doing nothing, and these individual studies likely include very different methodologies in very different cohorts of people at very different testing times in people with very different comorbidities, etc: ie, i would not necessarily put huge trust in comparing the numbers from the different studies...

-- there should also be more data on adherence to the various screening tests by patients and clinicians, including staying on the screening schedule as noted above

 

So, another guideline on colorectal cancer screening. Colorectal cancer screening is clearly one of the most beneficial ones we do and is based on lots of data. A few comments:

-- lowering the age to 45 does make sense, even though the colorectal cancer incidence in those 40-49yo is 1/5 that of those 60-69yo (though probably more if look only at 45-50yo), since this younger group have the most years-of-life to be gained and are more likely to have higher quality in those years from earlier detection of advanced adenoma or cancer (likely fewer chronic medical problems, etc)

-- and, i personally appreciate their approach of not distinguishing by race and highlighting that the real issue is developing systems to provide accessible high quality screening and followup programs to all, instead of a "blame-the-victim" approach

-- The ACA (Affordable Care Act) specifies that any Medicare-covered service recommended with a grade A or B by the USPSTF for any indication or population must be fully covered by Medicare, with no cost sharing for the patient; ie, these new recommendations should be covered by Medicare, which typically is generalized to other insurers in time.

geoff

 

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