In an updated recommendation statement, the U.S. Preventive Services Task Force (USPSTF) continues to strongly recommend screening for colorectal cancer for asymptomatic adults aged 50 through 75; but rather than emphasize specific screening strategies, it notes there are multiple screening strategies available.1 These strategies have “different levels of evidence to support their effectiveness, as well as unique advantages and limitations,” according to the recommendation statement, and choosing which to use should be a shared decision between patient and physician.
“The goal of the task force was to emphasize the fact that it was important an individual get screened and that there are many ways in which this can be accomplished,” USPSTF Chair Kirsten Bibbins-Domingo, PhD, MD, MAS, explained in an interview with The ASCO Post. Dr. Bibbins-Domingo also holds the Lee Goldman, MD, Endowed Chair in Medicine and is Professor of Medicine and of Epidemiology and Biostatistics at the University of California, San Francisco.
Best Test Is One That Gets Done
“Screening for colorectal cancer is a substantially underused preventive health strategy in the United States,” the task force wrote. “In addition, there are no empirical data to suggest that any of the strategies provide a greater net benefit. Accordingly, the best screening test is the one that gets done, and the USPSTF concludes that maximizing the total proportion of the eligible population that receives screening will result in the greatest reduction in colorectal cancer deaths.”
The phrase “the best screening test is the one that gets done” has drawn attention. “Philosophically that makes sense,” Robert E. Schoen, MD, MPH, Professor of Medicine and Epidemiology, Division of Gastroenterology, Hepatology, and Nutrition at the University of Pittsburgh School of Medicine, was quoted in the Pittsburgh Post-Gazette. “Colorectal cancer is one of the major success stories in medicine with a decline in incidence and mortality in the United States,” he revealed. “Screening has made a difference. That’s why the task force is pushing it. There is strong evidence that it works. We need to focus on getting more people screened and more cancers prevented.”2
An editorial accompanying the recommendation statement, published in The Journal of the American Medical Association (JAMA),3 noted: “A test can rank low when tested on a representative population but still be better aligned with an individual patient’s preferences and, therefore, be most likely to get done.”
The most important message of the recommendation statement, according to Dr. Bibbins-Domingo, is that a physician and patient decide together what test is best for that patient “and to make sure that that screening gets done.”
Review of the Evidence
To update the 2008 recommendations on colorectal cancer, the USPSTF reviewed the evidence on the effectiveness of different screening strategies in reducing the incidence of colorectal cancer and of colorectal cancer and all-cancer mortality, as well as the harms of the screening tests. “The USPSTF found convincing evidence that screening for colorectal cancer with several different methods can accurately detect early-stage colorectal cancer and adenomatous polyps,” according to the updated recommendation statement. The task force also found convincing evidence that screening in adults aged 50 to 75 reduces colorectal cancer mortality, but no method of screening for colorectal cancer was shown to reduce all-cause mortality in any age group.
“The USPSTF found no head-to-head studies demonstrating that any of the screening strategies it considered are more effective than others, although the tests have varying levels of evidence supporting their effectiveness, as well as different strengths and limitations,” which are listed in a table accompanying the article in JAMA.
Screening has made a difference. That’s why the task force is pushing it. There is strong evidence that it works. We need to focus on getting more people screened and more cancers prevented.— Robert E. Schoen, MD, MPH
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The USPSTF also commissioned the Cancer Intervention and Surveillance Modeling Network (CISNET) to conduct a comparative modeling study of the available screening methods. As described in the recommendation statement, “The [CISNET] models “estimated the number of life-years gained, colorectal cancer deaths averted, life-time colonoscopies required (as a proxy measure for the burden of screening), and resulting complications (ie, gastrointestinal and cardiovascular events) for various screening strategies, varying the age at which to start and stop screening and the frequency of screening.”
Assuming 100% adherence to screening beginning at age 50 and ending at age 75, four screening strategies “were estimated to provide an efficient balance of benefits and harms while also providing roughly comparable life-years gained.” These four strategies were colonoscopy every 10 years, fecal immunochemical test annually, flexible sigmoidoscopy every 10 years combined with annual fecal immunochemical test, and computed tomography (CT) colonography every 5 years. The models estimated these strategies would avert about 20 to 24 colorectal cancer deaths per 1,000 adults aged 50 to 75 years screened.
Varying Strengths and Limitations
In addition to those four tests, the updated recommendation statement includes the guaiac-based fecal occult blood test (gFOBT) performed annually, the multitargeted stool DNA test (FIT-DNA) performed every 1 or 3 years, and flexible sigmoidoscopy alone every 5 years. In the draft recommendation published and made available for public comment, these three were listed as alternative strategies, but the designations of recommended and alternative tests were found to be confusing, Dr. Bibbins-Domingo admitted.
“We received a large volume of public comments. It is a practice of the task force to review all of those comments, and then we use those comments to try to make sure our recommendation statements are as clear as possible to as many different types of audiences as possible,” she said. Therefore, the task force decided to list all the strategies, without recommending any specific ones, because there is evidence for all of the tests to suggest some net benefit.
“These tests are very different and have varying levels and bodies of evidence to support them. The different tests have their own benefits and limitations that might factor into a patient’s decision to use one test or another or a physician’s decision to recommend one test or another. What we wanted to do was to provide all of the information for doctors and patients to make the best decision together,” Dr. Bibbins-Domingo said.
“Different screening methods may be more or less attractive for patients based on their features,” the task force pointed out. “For example, colonoscopy requires a relatively greater time commitment over a short period (bowel preparation, procedure, and recovery) but allows for much longer time between screenings compared with stool-based screening. Stool-based screening requires persons to handle their feces, which may be difficult for some, but the test is quick and noninvasive and can be done at home (the sample is mailed to the laboratory for testing). Flexible sigmoidoscopy combined with annual FIT may be an attractive option for persons who want reassurance from endoscopic screening but want to limit their exposure to colonoscopy.”
First Blood-Based Screening Test
The first blood-based test for colorectal cancer screening approved by the U.S. Food and Drug Administration (FDA) detects circulating methylated SEPT9 DNA. The task force reported that a single study of the new test met the inclusion criteria for the systematic evidence review and “found the SEPT9 DNA test to have low sensitivity (48%) for detecting colorectal cancer.”
The FDA approval was made in April of this year, which Dr. Bibbins-Domingo noted was “between the time our recommendation statement was accepted and then finalized, and we deferred to the FDA recommendation labeling for that test, which views it as a secondary test.” She continued: “In all cases, we would like to see a body of evidence that helps us to understand the net benefit of any new test and where it fits into a primary screening strategy.”
A related article4 in JAMA noted: “Given the limited sensitivity of the test for cancer and polyps, blood-based screening may erode, not enhance, potential benefits of colorectal cancer screening.”
Potential Harms of Screening
“The harms of screening for colorectal cancer in adults aged 50 to 75 years are small,” according to the task force. “The majority of harms result from the use of colonoscopy, either as the screening test or as follow-up for positive findings detected by other screening tests.”
Among the favorable considerations listed for colonoscopy are less frequent screening and being able to perform screening and diagnostic follow-up of positive findings, such as removal of polyps, during the same examination. “Harms may be caused by bowel preparation prior to the procedure (eg, dehydration and electrolyte imbalances), the sedation used during the procedure (eg, cardiovascular events), or the procedure itself (eg, infection, colonic perforations, or bleeding),” the task force noted. Flexible sigmoidoscopy can also cause colonic perforations and bleeding, although less commonly than colonoscopy.
“Computed tomography colonography can result in unnecessary diagnostic testing or treatment of incidental extracolonic findings that are of no importance or would never have threatened the patient’s health or become apparent without screening (ie, overdiagnosis and overtreatment),” according to the task force. “I as a clinician believe and the task force believes as a core principle that patients need to understand benefits and harms of screening tests generally,” Dr. Bibbins-Domingo said, even though the potential harms “likely contribute to the low rate” of colorectal screening. “These are screening tests we are doing with patients who don’t have any signs or symptoms of disease. We are doing this to prevent something in the future. It is always essential that patients get informed consent, but it is especially critical for preventive tests that patients really understand both the potential benefits, which is why we recommend these tests, as well as the potential harms.”
When to Start and Stop Screening
The updated recommendation statement concerns only screening for colorectal cancer and as such only “applies to asymptomatic adults 50 years and older who are at average risk of colorectal cancer and who do not have a family history of known genetic disorders that predispose them to a high lifetime risk of colorectal cancer (such as Lynch syndrome or familial adenomatous polyposis), a personal history of inflammatory bowel disease, a previous adenomatous polyp, or previous colorectal cancer. When screening results in the diagnosis of colorectal adenomas or cancer, patients are followed up with a surveillance regimen, and recommendations for screening no longer apply.”
Colorectal cancer screening is recommended for those aged 50 to 75. This is a USPSTF grade A recommendation: “There is a high certainty that the net benefit is substantial.” For those aged 76 to 85 years, the decision to screen for colorectal cancer “should be an individual one, taking into account the patient’s overall health and prior screening history,” the task force recommended. This is a grade C recommendation: “There is at least moderate certainty that the net benefit is small.” Most likely to benefit in the group between age 76 and 85 are those who have never before been screened for colorectal cancer. Arguing against screening in older patients are comorbid conditions and limited life expectancy.
“The benefit of early detection and intervention for colorectal cancer in adults 86 years and older is at most small,” according to the task force. “Because the likelihood of benefit at this age is lower, it becomes even more important also to understand the harms of continued screening in this age group,” Dr. Bibbins-Domingo affirmed. ■
Disclosure: Dr. Bibbins-Domingo reported no potential conflicts of interest.
References
1. U.S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al: Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. JAMA 315:2564-2575, 2016.
3. Ransohoff DF, Sox HC: Clinical practice guidelines for colorectal cancer screening: New recommendations and new challenges. JAMA 315:2529-2531, 2016.
4. Parikh RB, Prasad V: Blood-based screening for colon cancer: A disruptive innovation of simply a disruption? JAMA 315:2519-2520, 2016.
