New colon cancer screening guidelines

The Multi-Society Task Force of Colorectal Cancer (MSTF), a combo of the Am College of Gastroenterology, Am Gastroenterological Assn, and the Am Society for Gastrointestinal Endoscopy, just published significantly revised guidelines on colorectal cancer (CRC) screening (see colon ca screening guideline ACG2017 in dropbox, or doi: 10.1038/ajg.2017.174 ).

Details:

--They differentiate between programmatic screening/screening done in an organized system which involves consistent planning, documentation, monitoring of quality, and follow-up (which exists in many industrialized countries, as well as some healthcare plans/medical organizations in the US) vs opportunistic screening, which is largely up to the provider or designee to identify patients who need screening and arrange it

-- given the potential for multiple different screens (9 are available), there are various approaches to the patient: offering the patient multiple options, though studies suggest that offering only 2 or 3 preferred options may improve patient adherence; sequential options, where the patient is offered a preferred option 1st, with subsequent options available if the 1st one were declined; or risk-stratified approach, where colonoscopy would be offered to those with a high likelihood or prevalence of advanced precancerous lesions (or potentially patients with higher than average risk, such as older patients, males, those with obesity, diabetes, or smoking), with other tests (eg FIT) being offered to patients at lower risk. 

Recommendations:

    -- offer CRC screening beginning at age 50 in average risk patients (strong recommendation, high quality evidence)

    -- any of the approaches of multiple screening options, sequential screening options, or risk stratified approaches are reasonable (weak recommendation, low quality evidence)

    --cascade of tests:

        --tier 1 tests: colonoscopy every 10 years, or annual FIT tests. (They prefer the former in sites where there are not good follow-up systems; also may be preferable in men older than 60, and women older than 65 with no prior screening)

        --tier 2 tests: CT colonography every 5 years, FIT-fecal DNA every 3 years, flexible sigmoidoscopy every 10 years (or every 5 years)

        --tier 3 tests: capsule colonoscopy every 5 years (and do not offer Septin 9)

Other considerations:

    -- family history: 

        --CRC in a first-degree relative increases the risk of CRC regardless the age of diagnosis of the affected relative, though the younger the relative, the greater the risk. 

        --family history of CRC diagnosed <60 years of age or for those with 2 first-degree relatives with CRC or advanced adenoma at any age: colonoscopy began at age 40 or 10 years before the age the relative was diagnosed, whichever comes first, with subsequent colonoscopy every 5 years. FIT testing should be offered to those who decline colonoscopy (a randomized trial showed there was a  trend favoring colonoscopy, but this was not significant).  (weak recommendation, low quality of evidence). prefer colonoscopy

        --family history of CRC or advanced adenoma in 1st degree relative diagnosed at age > 60 should have screening beginning at age 40, with normal testing intervals as above  (weak recommendation, very-low quality of evidence). prefer colonoscopy

    -- age: 

        --though the incidence of CRC in persons under age 50 is increasing,  the incidence remains low enough that they continue with 50 years old as the starting age overall, for non-African Americans​ (strong recommendation, moderate-quality of evidence).

        -- in African-American individuals, however, they suggest screening begin at age 45 (weak recommendation, very low quality evidence), since overall they have lower screening rates, higher incidence rates of CRC, early mean age at onset, worse survival and late-stage presentation, and a higher proportion of cancers before age 50. (weak recommendation, very-low quality of evidence): there are a few data suggesting benefit of screening African-Americans before age 50. see yesterday's blog: http://gmodestmedblogs.blogspot.com/2017/07/racial-disparities-in-interval.html ​ finding increased interval cancers in black persons soon after a "normal" routine colonoscopy

-- age to stop screening: potentially beneficial in persons up to age 86 if they have not previously been screened. Should be put in the perspective of comorbidities and life expectancy. Those with negative screening, especially by colonoscopy, could consider stopping at age 75, though MSTF also suggests the option of  continuing screening until life expectancy is less than 10 years (this is a variation supported by them, as opposed to stopping specifically at age 75, though they did note that this is a weak recommendation with low quality evidence). Consider screening up to age 85 if no prior screening has been done (also weak recommendation with low quality evidence). [But, the risks of colonoscopy increase in those over 75yo (eg, see http://gmodestmedblogs.blogspot.com/2015/04/risks-of-colonoscopy-in-older-people.html )]

Commentary:

-- adenomas are the precursors of about 70% of CRC's, and typically take more than 10 years to develop cancer, hence the 10 year suggested interval in those with normal colons and without genetic variants (eg Lynch syndrome). Invasive cancers from adenomas <5 mm is extremely rare, and is <1% in those 6-9 mm in size

-- one major concern with adenoma biopsies is the poor-to-moderate interobserver agreement in differentiating high- vs low-grade dysplasia by pathologists, as well as between tubular vs tubulovillous histology. Another concern is that sessile serrated polyps (SSP's) are particularly common in the proximal colon, are flat or sessile in shape, are difficult to detect a colonoscopy, and, other than hyperplastic polyps, and have a significant cancerous potential. However, there is also poor pathologist interobserver agreement in the differentiation of SSP's from hyperplastic polyps (!!!)

-- Colonoscopy has the clear advantages of high sensitivity for cancer and all classes of precancerous lesions, biopsy and diagnosis can be done right away, and there is a 10 year interval between examinations if all is normal. However, though the data are impressive through case-control studies as well as indirect trials (e.g. studies of fecal occult blood testing where large numbers of patients underwent colonoscopy), it is important to remember that there are no randomized trials of colonoscopy screening at this point. Disadvantages of colonoscopy include: thorough bowel prep (a pretty unpleasant procedure), higher risk of perforation than other modalities (0.5 per 1000), high risk of aspiration pneumonia with deep sedation, small risk of splenic injury, a greater risk of bleeding especially when biopsies are done (2.6 per 1000), and death (2.9 per 100,000). Also colonoscopy is operator-dependent, and they suggest that colonoscopists should have an adenoma detection rate greater than 25% (greater than 30% for males, greater than 20% for females), and cecal intubation rates should exceed 95%. and that patients ask/be aware of these numbers/ask the prospective colonoscopist

--FIT testing: noninvasive, one-time sensitivity for cancer 79%, about 30% sensitivity for advanced adenomas, low cost. Major disadvantage is need for repeated testing, poor or no sensitivity for serrated class precursor lesions (though there is no evidence that cancers arising from this class are less likely bleeds than those arising from adenomas). Given the requirement for annual testing, they suggest this is a more viable option in systems where there is programmatic screening available, and less dependent on clinicians remembering to offer annual screening. Although the sensitivity for FIT-DNA screening is higher (92% as well as 40% for SSP's > 1 cm), they dismiss it because of substantial decrease in specificity and high cost

-- flexible sigmoidoscopy: clearly reduce cancer incidence and or mortality in randomized trials. Lower cost and risk vs colonoscopy, more limited bowel preparation, no need for sedation. They also comment that the absence of sedation leads to low satisfaction experience for patients/less willingness to repeat the examination compared to colonoscopy (I wonder if this is really true). They do comment that there's no reason to think that sigmoidoscopy needs to be at done at 5 year intervals as previously recommended, but that 10 year intervals are probably reasonable. And there are other blogs suggesting even longer term benefit from a single sigmoidoscopy (see http://gmodestmedblogs.blogspot.com/2017/04/one-time-flex-sig.html was an observational study in UK finding decreased CRC incidence and mortality even after 17 years after a single sigmoidoscopy, as well as commenting on articles showing the benefits of colonoscopy for >15 years after a negative study)

-- there are specific recommendations in other documents by MSTF regarding the technical performance of both FIT testing and sigmoidoscopy/colonoscopy, in order to achieve high quality results

-- also, as they comment, "the best test is the one that gets done". I think this reinforces the need to use a patient-centered approach to ordering these tests instead of just prescribing one

so,

-- Some significant changes over prior recommendations, including placing the recommendations in tier groups instead of just listing them, elevating FIT testing to the top tier, and even suggesting that sigmoidoscopy could be done every 10 years

-- I have sent out several blogs in the past suggesting sigmoidoscopy as a viable option to colonoscopy, even though it clearly misses more proximal lesions. Sigmoidoscopy has fallen out of favor for a variety of reasons in the United States, including, as noted in this recommendation, the poor reimbursement and therefore less availability of this modality. The data are mixed on the importance of finding right-sided lesions, with some studies showing minimal mortality benefit in finding and excising them (ie, the major argument against sigmoidoscopy that it does not see the right side may not matter that much).​ It would be useful to have an RCT with clear clinical outcomes assessing the relative values of sigmoidoscopy and colonoscopy.

-- I must admit that I am quite impressed with the ease and acceptability for annual FIT testing, and the relatively low likelihood of requiring follow-up colonoscopy. However, I would certainly reiterate the MSTF concern about making sure there are systems to track this testing along with arranging for repeat testing. [As an aside, I should note that in Canada they recommend FIT testing every 2 years, see http://gmodestmedblogs.blogspot.com/2016/02/colorectal-screening-canada.html  , and they actually discourage using colonoscopy for screening, given the higher cost, conscious sedation (and need a driver to take patients home), an awful bowel clean-out,  more risk,  and lack of data showing benefit over FIT testing].