Draft Recommendation Statement
Colorectal Cancer: Screening
This opportunity for public comment expired on November 2, 2015 at 8:00 PM EST
Note: This is a Draft Recommendation Statement. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Recommendation Statement will be developed after careful consideration of the feedback received and will include both the Research Plan and Evidence Review as a basis.
Recommendations made by the USPSTF 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.
Draft: Recommendation Summary
|Adults ages 50 to 75 years|
The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years. The risks and benefits of different screening methods vary.
|The USPSTF recommends the service. There is high certainty that the net benefit is substantial.|
|Adults ages 76 to 85 years|
The decision to screen for colorectal cancer in adults ages 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history.
|The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.|
Colorectal cancer is the second leading cause of cancer death in the United States. In 2015, an estimated 133,000 persons will be diagnosed with the disease and about 50,000 will die from it. It is most frequently diagnosed among adults ages 65 to 74 years; the median age of death from colorectal cancer is 73 years.1
The USPSTF found convincing evidence that screening for colorectal cancer with several different methods can accurately detect early-stage colorectal cancer and adenomatous polyps.
Although single test performance is an important issue in the detection of colorectal cancer, the sensitivity of the test over time is more important in an ongoing screening program. However, data that permit assessment and direct comparison of screening methods to detect colorectal neoplasia in screening programs over time are limited to those from analytic modeling.
Benefits of Screening and Early Intervention
The USPSTF found convincing evidence that screening for colorectal cancer in adults ages 50 to 75 years reduces colorectal cancer mortality. Several screening strategies are effective (see the Clinical Considerations section and the Table). The USPSTF found no head-to-head studies that demonstrated that any of the recommended screening strategies (see Table) are more effective than others. Approximately one third of eligible adults in the United States have never been screened for colorectal cancer.2 As such, these recommended screening tests are not presented in any preferred or ranked order; rather, the goal is to maximize the total number of persons who are screened with any of the recommended screening tests, as that will have the largest impact on colorectal cancer deaths.
The benefit of early detection of and intervention for colorectal cancer declines after age 75 years. Among persons who have been previously screened for colorectal cancer, there is at best a moderate benefit to continuing screening from ages 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 age 86 years and older is at most small.
To date, no method of colorectal cancer screening has been shown to decrease all-cause mortality in any age group.3
Harms of Screening and Early Intervention
The harms of screening for colorectal cancer in adults ages 50 to 75 years are small. The majority of harms result from the use of colonoscopy, either as the screening test itself or as followup for positive findings detected by other screening tests. The rate of serious adverse events from colorectal cancer screening increases with age.3 Thus, the harms of screening for colorectal cancer in adults age 76 years and older are small to moderate.
The USPSTF concludes with high certainty that the net benefit (i.e., the benefit minus the harms) of screening for colorectal cancer in adults ages 50 to 75 years is substantial.
The USPSTF concludes with moderate certainty that the net benefit of screening for colorectal cancer in adults ages 76 to 85 years who have previously been screened is small. Adults who have never been screened for colorectal cancer are more likely to benefit.
Draft: Clinical Considerations
This recommendation applies to asymptomatic adults age 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 predisposes 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 with a surveillance regimen, and recommendations for screening no longer apply. The USPSTF did not review or consider the evidence on the effectiveness of any particular surveillance regimen after diagnosis and removal of adenomatous polyps or colorectal cancer.
Assessment of Risk
For the vast majority of adults, the most important risk factor for colorectal cancer is older age. About 4% of colorectal cancer cases occur in persons younger than age 50 years; the median age of diagnosis is 68 years.1
A positive family history (excluding known inherited familial syndromes) is thought to be linked to about 20% of cases of colorectal cancer.3 About 3% to 10% of the population has a first-degree relative with colorectal cancer.4 The USPSTF did not specifically review the evidence on screening in populations at increased risk; however, other professional organizations recommend that patients with a family history of colorectal cancer (a first-degree relative with early onset of colorectal cancer or multiple first-degree relatives with the disease) be screened at a younger age, more frequently, and with colonoscopy.5
Male sex and black race are also associated with higher colorectal cancer incidence and mortality. Blacks have the highest incidence and mortality rates compared with other racial/ethnic subgroups.1 The reasons for these disparities are not entirely clear. Studies have documented inequalities in screening, diagnostic followup, and treatment; they also suggest that equal treatment generally appears to produce equal outcomes.6-8 Accordingly, this recommendation applies to all ethnic and racial groups, with the clear acknowledgement that efforts are needed to ensure that at-risk populations receive recommended screening, followup, and treatment.
Recommended Screening Tests
The Table lists recommended screening tests for colorectal cancer, their intended frequency of use, and additional considerations about each method. The Figure presents the life-years gained, colorectal cancer deaths averted, and lifetime number of colonoscopies and noncolonoscopy tests required per 1,000 persons screened from ages 50 to 75 years for each of the recommended screening strategies.
Fecal Occult Blood Test and Fecal Immunochemical Test
Multiple randomized, controlled trials (RCTs) have shown that screening with the guaiac-based fecal occult blood test (gFOBT) reduces colorectal cancer deaths.3 The Hemoccult II® test (Beckman Coulter, Inc., Brea, CA) has largely been replaced in the United States by higher-sensitivity stool-based tests, such as the Hemoccult II SENSA® (Beckman Coulter, Inc., Brea, CA) or the fecal immunochemical test (FIT). Of the FITs that are cleared by the U.S. Food and Drug Administration and available for use in the United States, the OC-Light® test and the OC FIT-CHEK® family of FITs (Polymedco, Inc., Cortlandt Manor, NY) have the best test performance characteristics (i.e., highest sensitivity and specificity).3
The harms of stool-based tests primarily result from adverse events associated with colonoscopy performed for the followup of positive screening results.3
Flexible Sigmoidoscopy Combined With FIT
Flexible sigmoidoscopy combined with FIT has been studied in a single trial and was found to reduce the colorectal cancer–specific mortality rate more than flexible sigmoidoscopy alone.9 Modeling studies conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) in support of this recommendation also consistently predict that combined testing yields more life-years gained and colorectal cancer deaths averted compared with flexible sigmoidoscopy alone.10 Although several RCTs have shown that flexible sigmoidoscopy alone reduces deaths from colorectal cancer3 and is better than no screening at all, flexible sigmoidoscopy alone is inferior to a combined approach.
Flexible sigmoidoscopy, with or without FIT, can result in direct harms, such as colonic perforations and bleeding, although the associated event rates are much lower than those observed with colonoscopy.3 Harms can also occur as a result of followup colonoscopy, if diagnostic procedures are not performed as part of the sigmoidoscopy.
Completed trials of flexible sigmoidoscopy—a similar endoscopic screening method—provide indirect evidence that colonoscopy reduces colorectal cancer mortality, although they do not allow accurate estimation of the magnitude of effect and whether and how it differs between the two methods. A prospective cohort study also found an association between persons who self-reported being screened with colonoscopy and a lower colorectal cancer mortality rate.11
Colonoscopy has both indirect and direct harms. Harms may be caused by the bowel cleanout prior to the procedure (e.g., dehydration and electrolyte imbalances), the sedation used during the procedure (e.g., cardiovascular events), or the procedure itself (e.g., infection, colonic perforations, or bleeding).
Starting and Stopping Ages
Reported age ranges in the available RCTs of gFOBT and flexible sigmoidoscopy were 45 to 80 years and 50 to 74 years, respectively. For gFOBT, the majority of participants entered the trials at age 50 or 60 years, and for flexible sigmoidoscopy, the mean age of participants was 56 to 60 years.3 As previously noted, more than 95% of cases of colorectal cancer occur at age 50 years and older.1
Microsimulation analyses performed by CISNET suggest that starting colorectal cancer screening at age 45 rather than 50 years yields a modest increase in life-years gained and a more efficient balance between life-years gained and lifetime number of colonoscopies (a proxy for harms, such as colonic perforation and bleeding).10 However, across the different screening methods, lowering the age at which to begin screening to 45 years while maintaining the same screening interval resulted in an increase in the lifetime number of colonoscopies. In the case of screening colonoscopy, two of the three models found that when screening starts at age 45 years, the screening interval could be extended from 10 to 15 years. Doing so maintained the same (or slightly more) life-years gained as with performing colonoscopy every 10 years starting at age 50 years without increasing the lifetime number of colonoscopies. However, one model predicted a slight loss in life-years gained with a longer interval and an earlier age at which to begin screening.10 The USPSTF considered these findings and concluded that the evidence best supports a starting age of 50 years for the general population, noting the modest increase in life-years gained by starting screening earlier and the discordant findings across models for extending the screening interval when the age at which to begin screening is lowered, as well as a lack of empiric evidence in younger populations.
The age at which the balance of benefits and harms of colorectal cancer screening becomes less favorable varies based on a patient’s life expectancy, health status, the presence of comorbid conditions, and prior screening status.12 Empiric data from randomized trials on outcomes of screening after age 74 years are scarce. All three CISNET models consistently predict that few additional life- years are gained when screening is extended past age 75 years in average-risk persons who have previously received adequate screening.10
The USPSTF does not recommend routine screening for colorectal cancer in adults age 86 years and older. In this age group, competing causes of mortality preclude a mortality benefit that would outweigh the harms.
Evidence from RCTs demonstrates that annual or biennial screening with gFOBT reduces colorectal cancer deaths. Findings from the CISNET models support the following screening intervals for persons ages 50 to 75 years: 1) annual screening with FIT; 2) screening every 10 years with flexible sigmoidoscopy and annual screening with FIT; or 3) screening every 10 years with colonoscopy. These strategies yield comparable life-years gained (i.e., the life-years gained with the noncolonoscopy strategies were within 90% of those gained with the colonoscopy strategy) and an efficient balance of benefits and harms (see the full CISNET report for more details.)10 Of these three strategies, colonoscopy yields the most life-years gained but requires the largest number of lifetime colonoscopies. FIT yields the fewest life-years gained but also requires the fewest colonoscopies. Flexible sigmoidoscopy with annual FIT is in the middle for both measures (Figure).10
Treatment of early-stage colorectal cancer generally consists of local excision or simple polypectomy for tumors limited to the colonic mucosa, or surgical resection (laparoscopically or via open approach) with anastomosis for larger, localized lesions.
Screening with computed tomography (CT) colonography and multitargeted stool DNA (FIT-DNA) testing may be useful in select clinical circumstances. However, there is less mature evidence to support these methods, resulting in greater uncertainty about their net benefits and the most appropriate situations in which to use them.
The USPSTF found no studies that assessed the impact of screening with CT colonography on cancer incidence, morbidity, quality of life, or mortality.3 Although nine studies evaluated the sensitivity and specificity of CT colonography compared with colonoscopy to detect colorectal adenomas, none were designed to determine its diagnostic accuracy to detect colorectal cancer (the overall number of cancer cases in each study was limited).3 Empiric evidence on the optimal screening interval, if any, is lacking. CISNET modeling suggests that screening every 5 years with CT colonography (assuming colonoscopy followup for lesions measuring ≥6 mm) from ages 50 to 75 years could potentially yield approximately the same number of life-years gained, with a similar balance of benefits and harms, as the recommended strategies previously listed.10 However, CT colonography often requires cathartic bowel preparation; this burden is not captured in the primary proxy measure of harms as lifetime number of colonoscopies.
Extracolonic findings on CT colonography are common, occurring in approximately 40% to 70% of screening examinations.3 About 5% to 37% of these extracolonic findings require diagnostic followup, and about 3% need definitive treatment.3 These findings have the potential for both benefit and harm. Potential harms include additional diagnostic testing to determine that an abnormality is of no clinical importance, as well as treatment of findings that may never pose a threat to a patient’s health or even become apparent without screening (i.e., overdiagnosis and overtreatment). Radiation-induced cancer is a potential long-term concern with repeated use of CT colonography. No studies directly measured this risk, but radiation exposure during the procedure appears to be low, with a maximum of about 7 mSv per examination.3 In comparison, annual background radiation exposure in the United States is 3 mSv per year per person. Although seven new studies have examined the potential harms associated with CT colonography since the prior USPSTF review,3 high-quality evidence remains lacking to draw clear conclusions about the ultimate clinical impact associated with the detection and subsequent workup of extracolonic findings. Given the frequency with which these incidental findings occur, it is difficult to accurately bound the potential net benefit of this screening test without this information.
The USPSTF found no studies that assessed the impact of screening with FIT-DNA on cancer incidence, morbidity, quality of life, or mortality.3 One study compared the sensitivity and specificity of the only FIT-DNA screening test available in the United States with FIT alone and colonoscopy for the detection of colorectal cancer and found that FIT-DNA was more sensitive but less specific than FIT alone.13 Evidence on the optimal screening interval, if any, is lacking. CISNET modeling suggests that annual screening with FIT-DNA from ages 50 to 75 years could potentially yield approximately the same number of life-years gained as the recommended strategies previously listed.10 However, compared with other stool-based screening tests and screening with colonoscopy every 10 years, FIT-DNA requires a larger number of lifetime colonoscopies (a proxy for the harms of screening) per life-year gained.
Harms associated with FIT-DNA largely arise from diagnostic colonoscopy performed after positive screening results. Since the specificity of FIT-DNA is lower than that of FIT,3 the number of false-positive results, and the likelihood of experiencing an adverse event related to diagnostic colonoscopy, are increased. A theoretical concern about FIT-DNA is whether its use might lead to more frequent and invasive followup testing in persons who are not at increased risk of colorectal cancer because of patient or clinician concerns about abnormal DNA results. There are no data that evaluate how to implement FIT-DNA into a longitudinal colorectal cancer screening program.
Multitargeted stool DNA testing can be viewed simply as a more sensitive but less specific stool-based test than FIT. However, the theoretical advantage of the test is the stool DNA component. At present, there is only one fair-quality study that compares the sensitivity and specificity of a single FIT-DNA test with FIT.3 While modeling can be used to understand the impact of the test’s reduced specificity and increased false-positive rate, empiric evidence is lacking on appropriate followup of abnormal results, making it difficult to accurately bound the potential net benefit of this screening test.
Other Approaches to Prevention
The USPSTF is updating its recommendation on the use of aspirin to prevent cardiovascular disease and colorectal cancer in average-risk adults. The draft and final recommendation statement (when available) can be found on the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Draft: Other Considerations
Colorectal cancer is the cause of substantial morbidity and mortality, and the evidence is convincing that screening for colorectal cancer reduces that burden. Despite the availability of several effective screening options, nearly one third of eligible adults have never been screened.14 Different screening methods may be more or less attractive for patients based on their features. For example, colonoscopy requires a relatively greater time commitment over a short period of time (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 off-putting to some, but is a quick, noninvasive test that can be done at home (the sample is mailed to the laboratory for results). Flexible sigmoidoscopy combined with annual FIT may be an attractive option for those who want reassurance from endoscopic screening but wish to limit their exposure to colonoscopy, or those who live in geographic locations where access to screening colonoscopy is limited or not available. Given the lack of evidence from head-to-head comparative trials that any of the recommended tests have a greater net benefit than the others, clinicians should consider engaging patients in informed decisionmaking about the screening strategy that would most likely result in completion, with high adherence over time, taking into consideration both the patient’s preferences and local availability.
In order for colorectal cancer screening programs to be successful in reducing deaths from the disease, they need to involve more than just the screening method in isolation. Screening is a package or cascade of activities that must occur in concert, cohesively, and in an organized way for benefits to be realized, from the point of provision of the initial screening examination (including related interventions or services, such as bowel preparation or sedation with endoscopy, that are required for successful administration of the screening test) to the timely receipt of any necessary diagnostic followup and treatment.
Multiple effective implementation strategies have been demonstrated to increase appropriate provision and use of colorectal cancer screening. Specifically, the Community Preventive Services Task Force recommends the use of clinician and client reminder systems, the use of small media (such as videos, letters, and brochures), reducing structural barriers to screening (such as the time or distance to the screening delivery setting or offering extended or nonstandard clinic hours), and providing clinician assessment and feedback about screening rates (available at www.thecommunityguide.org/cancer).
Lastly, clinicians also need to consider how they will engage patients older than age 75 years about when to stop screening.
Research Needs and Gaps
Higher quality data are needed about the natural history of small (<10 mm) adenomas to improve understanding of optimal screening strategies and to guide when clinical intervention is required. Further, because determining the ultimate worth of a screening method requires an accurate assessment of the net benefit of that intervention, randomized trials are needed to directly compare different types of colorectal cancer screening programs to more clearly define their relative benefits and harms.
Modeling suggests there may be some potential advantages to starting colonoscopy screening at an earlier age (45 years) and to extending the screening interval between negative examinations. This approach could be evaluated in a future clinical trial.
Although there is a growing body of evidence on the test performance characteristics of CT colonography, evidence is still lacking to bound the potential harms of this technology, particularly in regard to incidental findings. More consistent and complete reporting, in studies with longer-term followup, of the downstream consequences of initial detection, subsequent workup, and definitive treatment of extracolonic findings (E3 and E4) from CT colonography would allow for better understanding of the net benefit associated with this screening approach.
Empiric evidence is lacking on appropriate followup of abnormal results from FIT-DNA screening. Additional research to replicate the results of a previous diagnostic accuracy study, as well as to document that the problem of a greater number of inadequate test samples with FIT-DNA than FIT alone13 has indeed been resolved, as stated by the manufacturer,15 would also be useful.
Studies on patient adherence to the various screening options, within single-method programs of screening over time, as well as factors that may influence adherence across different screening methods, are needed to help better inform and improve uptake of screening across eligible populations.
Scope of Review
The USPSTF commissioned a systematic evidence review3 to update its 2008 recommendation on screening for colorectal cancer. The review addresses: 1) the effectiveness of colonoscopy, flexible sigmoidoscopy, CT colonography, gFOBT, FIT, multitargeted stool DNA testing, and methylated Septin 9 DNA testing in reducing incidence of and mortality from colorectal cancer or all-cause mortality; 2) the harms of these screening tests; and 3) the test performance characteristics of these tests for detecting adenomatous polyps and/or advanced adenomas based on size, as well as colorectal cancer. In contrast to the evidence review performed for the USPSTF in 2008, this review expanded its approach to additionally search for and consider: 1) observational evidence about the benefits of screening tests when trial evidence does not exist, and 2) comparative effectiveness studies of screening tests on cancer incidence and mortality.
Additionally, the USPSTF commissioned a report from the CISNET Colorectal Cancer Working Group10 to provide information from comparative modeling on optimal starting and stopping ages and screening intervals across the different available methods. Compared with the previous decision analysis performed for the USPSTF, this analysis used more narrowly defined ages at which to begin and end screening and for screening intervals. It also includes new screening methods (multitargeted stool DNA testing, CT colonography, and flexible sigmoidoscopy combined with FIT), updated test characteristics, and age-specific risks of colonoscopy complications.
Accuracy of Screening Tests
All of the available studies of the test characteristics of different screening methods evaluated one-time application of the examination. As such, it is not possible to draw meaningful inferences about the ultimate performance of these tests as intended in a real-world setting (i.e., in a program of repeated screening over time).
High-sensitivity gFOBT (Hemoccult II SENSA) has a sensitivity of 62% to 79% and a specificity of 87% to 96% for detecting colorectal cancer.3 FITs can be grouped according to whether they are qualitative (fixed cutoff) or quantitative (adjustable cutoff) assays; overall, test performance among this class of stool-based tests varies widely. Sensitivity and specificity of the OC-Light test using a cutoff of 10 μg/g to detect colorectal cancer ranges from 79% to 88% and 91% to 93%, respectively (3); sensitivity and specificity of the OC FIT-CHEK family of tests using a cutoff of 20 μg/g to detect colorectal cancer, as directed by the manufacturer, ranges from 73% to 75% and 91% to 95%, respectively.3 In the single study assessing the test characteristics of the only multitargeted stool DNA test available in the United States, its sensitivity and specificity for colorectal cancer was 92% (95% confidence interval [CI], 84% to 97%) and 84% (95% CI, 84% to 85%), respectively.13
Colonoscopy is generally considered to be the criterion standard for test characteristic studies, although it can and does miss some cases of colorectal cancer. No studies have evaluated the test performance characteristics of flexible sigmoidoscopy against a colonoscopy standard in an average-risk screening population.3 Studies of CT colonography have not been powered to estimate its ability to detect cancer. Studies of CT colonography test performance with bowel preparation found that the per-person sensitivity to detect adenomas measuring 10 mm or larger ranged from 67% to 94%; specificity ranged from 86% to 98%. Only two studies evaluated the performance of CT colonography without bowel preparation; they found sensitivity and specificity for adenomas measuring 10 mm or larger ranging from 67% to 90% and 85% to 97%, respectively.3
Effectiveness of Early Detection and Treatment for Recommended Tests
The Hemoccult II test was the first colorectal cancer screening test demonstrated to reduce disease-specific mortality in an RCT. Six trials show that after 11 to 30 years of followup, screening with gFOBT reduces the risk of colorectal cancer death by about 9% to 22% when used biennially (about 9 to 16 fewer colorectal cancer deaths per 100,000 person-years), or about 32% when used annually.3 As noted previously, in the United States, the Hemoccult II test has largely been superseded by higher-sensitivity stool-based tests, such as the Hemoccult II SENSA or FITs.
Flexible sigmoidoscopy has also been assessed in multiple RCTs. Pooled meta-analysis of four trials demonstrates that one-time flexible sigmoidoscopy reduces the risk of dying of colorectal cancer by 27% after approximately 11 to 12 years (incidence rate ratio, 0.73 [95% CI, 0.66 to 0.82]), or about 9 to 14 fewer colorectal cancer deaths per 100,000 person-years.3 The Norwegian Colorectal Cancer Prevention Trial found that its flexible sigmoidoscopy plus FIT arm had a lower colorectal cancer–specific mortality rate than the flexible sigmoidoscopy only arm (hazard ratio [HR], 0.62 [95% CI, 0.42 to 0.90] vs. 0.84 [95% CI, 0.61 to 1.17]).9 CISNET models found that flexible sigmoidoscopy screening from ages 50 to 75 years, repeated every 5 years, would result in approximately 181 to 227 life-years gained per 1,000 persons screened over a lifetime. However, a combined approach of flexible sigmoidoscopy repeated every 10 years with annual FIT screening would result in approximately 246 to 270 life-years gained per 1,000 persons screened (although it would be accompanied by an increase in the total number of diagnostic and surveillance colonoscopies required).10
No RCTs have evaluated the effect of colonoscopy on colorectal cancer mortality, although several are in progress (Spanish COLONPREV, Swedish SCREESCO, and U.S. CONFIRM trials),16-19 including one (Northern European Initiative on Colorectal Cancer trial) with a control arm of no screening.17 One large (n=88,902) fair-quality prospective cohort study combining data from the Nurses’ Health Study and the Health Professionals Followup Study found an association between self-reported receipt of screening colonoscopy and reduced distal and proximal colorectal cancer mortality (multivariate HR, 0.18 [95% CI, 0.10 to 0.31] and 0.47 [95% CI, 0.29 to 0.67], respectively).11 Although the investigators adjusted for known potential risk factors for colorectal cancer, given the study design, they could not address unknown or unmeasured confounders. Additionally, it is unclear based on the design whether the benefit accrued from one or multiple colonoscopies or screening plus surveillance colonoscopy. Overall, the study likely overestimates the magnitude of benefit associated with colonoscopy; the observed effect size in this study also cannot be directly compared with that measured in randomized trials of other colorectal cancer screening methods.
CISNET models commissioned for this review projected the estimated life-years gained and required number of lifetime colonoscopies (as a proxy measure for harms) for various screening strategies, varying the age at which to start and stop and the frequency of screening. With an age to begin screening of 50 years and an age to end screening of 75 years, assuming 100% adherence with screening over a lifetime, three of the recommended strategies emerged as efficient while also providing roughly comparable life-years gained: colonoscopy every 10 years, annual FIT, and flexible sigmoidoscopy every 10 years combined with annual FIT. Over a lifetime, CISNET models predicted these strategies would produce about 231 to 275 life-years gained, or about 20 to 24 colorectal cancer deaths averted per 1,000 persons screened from ages 50 to 75 years.10
Harms of Early Detection and Treatment for Recommended Tests
The USPSTF found adequate evidence of harms associated with different colorectal screening programs. With all screening methods, a positive test result leads to followup colonoscopy to resolve the diagnosis; colonoscopy represents the chief source of harms associated with colorectal cancer screening. As an invasive procedure, colonoscopy can result in both indirect and direct harms, and can produce important morbidity as well as anxiety and discomfort. Bowel preparation may lead to dehydration or electrolyte imbalances, particularly in older adults or those with comorbid conditions; accurate estimates of the rates of these events are not available. If sedation is used during colonoscopy, cardiopulmonary events may uncommonly occur; the precise frequency of occurrence is also not known.
The direct harms of endoscopy have been somewhat better studied.3 Pooled estimates suggest there are about four (95% CI, 2 to 5) colonic perforations and about eight (95% CI, 5 to 14) major intestinal bleeding episodes per 10,000 screening colonoscopies. Many of these events appear to be related to polypectomy, and the risk of experiencing an adverse event increases with age.3 The risk of bleeding or perforation appears to be greater if the colonoscopy is done as part of diagnostic followup for a positive screening test of a different method; for example, pooled data from flexible sigmoidoscopy trials found about 14 (95% CI, 9 to 26) colonic perforations and 24 (95% CI, 5 to 63) major bleeding episodes per 10,000 persons undergoing diagnostic colonoscopy.3 This compares with about one perforation and two major bleeding episodes per every 10,000 flexible sigmoidoscopies performed for the purposes of cancer screening.3
The harms from a single administration of a screening test must be considered in the context of how often the test will be repeated over a patient’s lifetime. In the case of colorectal cancer screening, this means considering how many colonoscopies (the chief source of serious harms) will be required to follow up on abnormal screening test results. Of the three recommended screening strategies, CISNET modeling suggests that annual FIT screening has the least number of total colonoscopies per 1,000 persons screened over a lifetime and colonoscopy every 10 years has the most.10
Estimate of Magnitude of Net Benefit
The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults ages 50 to 75 years is of substantial net benefit. There are several effective screening strategies to choose from, including high-sensitivity stool-based testing with FIT or gFOBT, flexible sigmoidoscopy combined with FIT, and colonoscopy.
For older adults ages 76 to 85 years, the benefits of screening for colorectal cancer decline, and the risk of experiencing serious associated harms increases. The most important consideration for clinicians and patients in this age group is whether the patient has previously been screened. Persons in this age group who have never been screened for colorectal cancer are more likely to benefit than those who have previously been screened. Other factors that should be considered include whether the patient has other chronic health conditions and would be well enough to undergo treatment if cancer was found.
Screening for colorectal cancer is a substantially underused preventive health strategy in the United States.14 Additionally, there is no empiric data to suggest that any of the recommended 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 with one of the recommended tests will result in the greatest reduction in deaths due to colorectal cancer.
Draft: Update of Previous USPSTF Recommendation
This recommendation updates the 2008 USPSTF recommendation.20 The USPSTF continues to recommend screening with colonoscopy every 10 years, annual FIT, and annual high-sensitivity gFOBT. The 2008 recommendation included screening with flexible sigmoidoscopy every 5 years combined with either FIT or gFOBT every 3 years. The current recommendation only includes flexible sigmoidoscopy combined with FIT, and the interval for this screening strategy has changed to flexible sigmoidoscopy every 10 years with annual FIT. These changes are the result of alterations in the specific strategies and updated estimates of test performance included in the most recent CISNET analysis.
Draft: Recommendation of Others
Many organizations have issued guidelines concerning screening for colorectal cancer. All of the following recommendations apply to average-risk adults age 50 years and older.
In 2008, the American Cancer Society, American College of Radiology, and the U.S. Multi-Society Task Force (including the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy) jointly issued recommendations. They prioritized flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, double-contrast barium enema every 5 years, and CT colonography every 5 years as preferred tests “designed to both prevent and detect cancer” if resources are available, but also recommended annual high-sensitivity gFOBT or FIT and stool-based DNA testing (interval uncertain).5. Shortly thereafter, the American College of Gastroenterology released an independent guideline that recommended colonoscopy every 10 years as the single preferred screening strategy. It stated that if colonoscopy is not available or is unacceptable to a patient, recommended alternative strategies include (preferred) flexible sigmoidoscopy every 5 to 10 years or CT colonography every 5 years or (acceptable) annual FIT, annual Hemoccult II SENSA, or stool-based DNA testing every 3 years.21
In 2012, the National Comprehensive Cancer Network recommended colonoscopy every 10 years as the preferred screening strategy if available; otherwise, it recommended annual gFOBT or FIT with or without flexible sigmoidoscopy every 5 years or flexible sigmoidoscopy alone every 5 years as secondary approaches to screening.22
In 2015, the American College of Physicians recommended that average-risk adults ages 50 to 75 years should be encouraged to be screened for colorectal cancer by one of four strategies: 1) annual high-sensitivity gFOBT or FIT; 2) flexible sigmoidoscopy every 5 years; 3) combined high-sensitivity gFOBT or FIT every 3 years plus flexible sigmoidoscopy every 5 years; or 4) colonoscopy every 10 years. It advised that average-risk adults younger than age 50 years, older than age 75 years, or with an estimated life expectancy of less than 10 years should not be screened.23 The American Academy of Family Physicians is in the process of updating its guidelines.24
1. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, et al (eds). SEER Cancer Statistics Review, 1975–2012. Bethesda, MD: National Cancer Institute; 2015. Accessed at http://seer.cancer.gov/csr/1975_2012/ on September 22, 2015.
2. Shapiro JA, Klabunde CN, Thompson TD, Nadel MR, Seeff LC, White A. Patterns of colorectal cancer test use, including CT colonography, in the 2010 National Health Interview Survey. Cancer Epidemiol Biomarkers Prev. 2012;21(6):895-904.
3. Lin JS, Piper M, Perdue LA, Rutter C, Webber EM, O’Connor E, et al. Screening for Colorectal Cancer: An Updated Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 135. AHRQ Publication No. 14-05203-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2015.
4. Henrikson NB, Webber EM, Goddard KA, Scrol A, Piper M, Williams MS, et al. Family history and the natural history of colorectal cancer: systematic review. Genet Med. 2015;17(9):702-12.
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Draft: Table. Recommended Screening Strategies for Colorectal Cancer
|Screening Modality||Frequency*||Other Considerations|
|FIT or high-sensitivity gFOBT||Every year||Requires the fewest lifetime colonoscopies (a proxy for harms). Does not require bowel cleanout, anesthesia, or transportation to and from the screening examination (test is performed at home).|
|Flexible sigmoidoscopy with FIT||Flexible sigmoidoscopy every 10 years plus FIT every year||Potentially attractive option for persons who want endoscopic screening but wish to limit exposure to colonoscopy. May also be useful when access to colonoscopy is geographically limited.|
|Colonoscopy||Every 10 years||Requires less frequent screening. Screening and diagnostic followup of positive results can be performed during the same examination.|
* Applies to persons with negative screening tests (including hyperplastic polyps) and is not intended for those in surveillance programs.
Abbreviations: FIT=fecal immunochemical test; gFOBT=guaiac-based fecal occult blood test.
Draft: Figure. Benefits, Harms, and Burdens of Recommended Screening Strategies Over a Lifetime*†
* Outcomes from CISNET models.10 In the models, gFOBT 1y does not provide an efficient balance of benefits and harms compared with other stool-based screening modalities.
† Results are plotted as the median, with the range across the three CISNET models in parentheses.
Abbreviations: CISNET=Cancer Intervention and Surveillance Modeling Network; FIT=fecal immunochemical test; gFOBT=high-sensitivity guaiac-based fecal occult blood test; SIG=flexible sigmoidoscopy; COL=colonoscopy.
The Figure shows outcomes for the set of model-recommended strategies, with an age to begin screening of 50 and an age to end screening of 75, assuming colonoscopy strategy with a 10-year interval is selected. Outcomes include the number of life-years gained, colorectal cancer deaths averted, colonoscopies required, and noncolonoscopy tests, all per 1,000 persons screened. The recommended strategies are annual FIT, CT colonography every 5 years, flexible sigmoidoscopy every 10 years with annual FIT, and colonoscopy every 10 years.
Internet Citation: Draft Recommendation Statement: Colorectal Cancer: Screening. U.S. Preventive Services Task Force. October 2015.