Colorectal cancer is the third leading cause of cancer death for both men and women, with an estimated 53,200 persons dying from colorectal cancer in the United States in 2020.¹ Colorectal cancer is most frequently diagnosed among persons ages 65 to 74 years.² It is estimated that 10.5% of new colorectal cancer cases occur in persons younger than age 50 years.³ Recent epidemiological data suggest that colorectal cancer incidence in 45-year-old adults now approaches that of persons age 50 years in the era prior to the introduction of routine screening.⁴ In 2016, about one-quarter of eligible adults in the United States had never been screened for colorectal cancer.⁵

The USPSTF concludes with high certainty that the net benefit 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 45 to 49 years is moderate.

The USPSTF concludes with moderate certainty that the net benefit of screening for colorectal cancer in adults ages 76 to 85 years who have been previously screened is small. Adults who have never been screened for colorectal cancer are more likely to benefit. 

This assessment of net benefit applies to stool-based tests with high sensitivity, colonoscopy, computed tomography (CT) colonography, and flexible sigmoidoscopy. See Table 1 for characteristics of recommended screening strategies. The USPSTF recommendation for screening for colorectal cancer does not include serum tests, urine tests, or capsule endoscopy for colorectal cancer screening because of the limited available evidence on these tests, and because other effective tests (i.e., the recommended screening strategies) are available. 

See Table 2 for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPTSF uses to determine net benefit, see the USPSTF Procedure Manual.⁶

Patient Population Under Consideration

This recommendation applies to asymptomatic adults age 45 years and older who are at average risk of colorectal cancer (i.e., no prior diagnosis of colorectal cancer, adenomatous polyps, or inflammatory bowel disease or 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]). 

Assessment of Risk

Age is one of the most important risk factors for colorectal cancer, with incidence rates increasing with age, and nearly 94% of new cases of colorectal cancer occurring in adults age 45 years and older.² Rates of colorectal cancer are higher in Black adults,² persons with a family history of colorectal cancer (even in the absence of any known inherited syndrome such as Lynch syndrome or familial adenomatous polyposis),⁷ and men.² However, all adults age 45 years and older are at risk for colorectal cancer and should be offered screening, even if these risk factors are absent. 

Screening Tests

The risks and benefits of different screening tests vary. See Table 1 for characteristics of recommended screening strategies, which may include combinations of screening tests. Because of limited available evidence, the USPSTF recommendation does not include serum tests, urine tests, or capsule endoscopy for colorectal cancer screening. Recommended stool-based and direct visualization screening tests are described below.

Stool-Based Tests

Stool-based tests include the high-sensitivity guaiac-based fecal occult blood test (HSgFOBT), fecal immunochemical test (FIT), and stool DNA test. Both HSgFOBT and FIT detect blood in the stool; however, they use different methods. HSgFOBT is based on chemical detection of blood, while FIT uses antibodies to detect blood.⁸ Stool DNA tests detect DNA biomarkers for cancer in cells shed from the lining of the colon and rectum into stool.⁸ Currently, the only stool DNA test approved by the U.S. Food and Drug Administration is a multitarget stool DNA test that also includes a FIT component, referred to as sDNA-FIT in this recommendation. Among the stool-based tests, screening with annual FIT or annual sDNA-FIT provides greater life-years gained than annual HSgFOBT or sDNA-FIT every 3 years.⁹ Additionally, screening with sDNA-FIT annually would result in more colonoscopies than annual screening with FIT.⁹ Currently, there is uncertainty around the accuracy of HSgFOBT to detect colorectal cancer and advanced adenomas, although it is likely lower than the accuracy of other stool-based methods, and HSgFOBT is more difficult for patients to administer.¹⁰

Direct Visualization Tests

Direct visualization tests to screen for colorectal cancer include colonoscopy, CT colonography, and flexible sigmoidoscopy. All three screening tests visualize the inside of the colon and rectum, although flexible sigmoidoscopy can only visualize the rectum, sigmoid colon, and descending colon while colonoscopy and CT colonography can generally visualize the entire colon. For colonoscopy and flexible sigmoidoscopy, a camera is used to visualize the inside of the colon, while CT colonography uses x-ray images. Among the direct visualization tests, a colonoscopy every 10 years or CT colonography every 5 years have greater life-years gained than flexible sigmoidoscopy every 5 years.⁹ Unlike colonoscopy and flexible sigmoidoscopy, CT colonography may reveal extracolonic findings that require additional work-up, which could lead to other potential benefits or harms.¹⁰

Starting and Stopping Ages

The USPSTF recommends offering colorectal cancer screening starting at age 45 years. Although the absolute risk of developing colorectal cancer is much lower in adults younger than age 50 years (20.0 new colorectal cancer cases per 100,000 persons ages 40 to 49 years, 47.8 new cases per 100,000 persons ages 50 to 59 years, and 105.2 new cases per 100,000 persons age 60 years and older¹¹), age-period-cohort analysis indicates a recent trend for increasing risk of colorectal cancer in adults younger than age 50 years.⁴ Additionally, modeling performed by the Cancer Intervention and Surveillance Modeling Network (CISNET) suggests that starting colorectal cancer screening at age 45 years can moderately increase life-years gained and decrease colorectal cancer cases and deaths compared to beginning screening at age 50 years.⁹

In adults ages 76 to 85 years, the age at which the balance of benefits and harms of colorectal cancer screening becomes less favorable and screening should be stopped varies based on a patient’s health status (e.g., life expectancy, comorbid conditions) and prior screening status.¹² Limited evidence suggests harms from colonoscopy, such as perforation and bleeding, and extracolonic findings on CT colonography increase with age.¹⁰ Modeling studies estimate that generally, few additional life-years are gained when screening is extended past age 75 years among average-risk adults who have previously received adequate screening.⁹

In adults age 86 years and older, competing causes of mortality preclude a mortality benefit that would outweigh the harms. 

Screening Intervals

Recommended intervals for colorectal cancer screening tests include:

• Annual screening with HSgFOBT, FIT, or sDNA-FIT
• sDNA-FIT every 3 years
• CT colonography every 5 years
• Flexible sigmoidoscopy every 5 years
• Flexible sigmoidoscopy every 10 years + annual FIT
• Colonoscopy screening every 10 years

Treatment or Interventions

Localized disease is generally treated with surgical resection.¹³ Additional treatment options include adjuvant chemotherapy, neoadjuvant chemotherapy, and targeted therapies.¹³

Screening for Colorectal Cancer in Black Adults 

Burden

Black adults have the highest incidence of and mortality from colorectal cancer compared to other races/ethnicities. From 2013 to 2017, incidence rates for colorectal cancer were 43.6 cases per 100,000 Black adults, 37.8 cases per 100,000 white adults, 31.8 cases per 100,000 Asian/Pacific Islander adults, 39.0 cases per 100,000 American Indian/Alaska Native adults, and 33.7 cases per 100,000 Hispanic/Latino adults.¹⁴ Colorectal cancer death rates were 18.5 deaths per 100,000 Black adults, 13.6 deaths per 100,000 white adults, 9.6 deaths per 100,000 Asian/Pacific Islander adults, 15.8 deaths per American Indian/Alaska Native adults, and 11.1 deaths per 100,000 Hispanic/Latino adults.¹⁴ It is unclear whether the primary driver for this health disparity is biology, access to and utilization of colorectal cancer screening and treatment, or disparities in the quality of screening and treatment, although recent evidence points to the last.^15,16 The recent trend for increasing colorectal cancer incidence in adults younger than age 50 years has been observed in white and Hispanic/Latino adults, but not Black or Asian/Pacific Islander adults.¹⁷ However, despite these trends, Black adults across all age groups, including those younger than age 50 years, continue to have a higher incidence of and mortality from colorectal cancer than white adults. 

Available Evidence

The USPSTF sought evidence on the potential benefits and harms of colorectal cancer screening in Black adults; however, little empirical evidence was identified. Although some studies on the effectiveness of colorectal cancer screening included non-white participants, no studies reported results of screening by race/ethnicity.¹⁰ Few studies on screening accuracy reported findings by race; however, those studies that did generally found no difference in accuracy to detect colorectal cancer in Black adults compared to white adults for FIT (in one study) or sDNA-FIT (in one study). The four studies of screening colonoscopy that reported harms by race/ethnicity had inconsistent findings. No other studies on harms reported results by race/ethnicity. Modeling studies that assume perfect adherence to screening, no racial differences in screening accuracy or natural history of colorectal cancer (i.e., no biological differences in the risks of adenoma onset and progression to colorectal cancer),¹⁶ but lower relative colorectal cancer survival rates¹⁸ and increased all-cause mortality in Black vs. white adults.¹⁹ estimate similar life-years gained from screening Black and white adults and a similar balance of the benefits and harms for each screening strategy.¹¹ 

Advising Black Adults

Based on the limited available evidence, the USPSTF is not able to make a separate, specific recommendation on colorectal cancer screening in Black adults. Other organizations such as the U.S. Multi-Society Task Force recommend starting screening in Black adults at age 45 years, while starting screening at age 50 years for persons of other races.²⁰ The current USPSTF draft statement recommends starting screening for everyone at age 45 years, including Black adults.

Results from CISNET modeling did not support different screening strategies by race. The USPSTF recognizes the higher colorectal cancer incidence and mortality in Black adults and strongly encourages clinicians to ensure their Black patients receive recommended colorectal cancer screening, followup, and treatment. The USPSTF encourages the development of systems of care to ensure adults receive high-quality care across the continuum of screening and treatment, with special attention to Black communities experiencing worse health outcomes. 

Implementation

Each screening test has different considerations for implementation that may act to facilitate uptake of and adherence to screening or serve as a barrier to screening (see Table 1 for additional details). Implementation considerations include where the screening test is performed, who performs the screening procedure, the need for pre-procedure bowel preparation, the need for sedation during the test, and followup procedures for abnormal findings on a screening test. These considerations have implications for how feasible and preferable a given screening test is for an individual. Discussion of implementation considerations with patients may help better identify screening tests that are more likely to be completed by a given individual. 

Stool-Based Tests

Stool-based screening requires people 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), and no bowel preparation is needed to perform the screening test. The benefits of stool-based testing accrue over frequent, repeated testing, thus requiring commitment and adherence to screening intervals to achieve a substantial benefit in decreased colorectal cancer mortality. Work-up of positive results on stool-based screening tests requires followup diagnostic colonoscopy for the screening benefits to be achieved. Screening with HSgFOBT requires some dietary and medication restrictions prior to collecting stool samples²¹ while FIT and sDNA-FIT^22,23 do not. Test specimens can be collected from a single stool sample with FIT and sDNA-FIT^22,23 (sDNA-FIT involves collecting an entire bowel movement) while collection of samples from three separate bowel movements are required for HSgFOBT screening.²¹ 

Direct Visualization Tests

Screening by direct visualization tests must be performed in a clinical setting rather than in the home. When performed alone, direct visualization tests allow for a much longer time between screenings compared to stool-based screening. Colonoscopy allows the longest length between screenings (10 years), while flexible sigmoidoscopy and CT colonography allow 5 years between screenings if performed alone. Direct visualization tests all require bowel preparation prior to the screening test, although the preparation involved with CT colonography is usually less intensive than for colonoscopy or flexible sigmoidoscopy.²⁴ The use of sedation or anesthesia during the procedure also varies by screening test. Sedation or anesthesia is usually used during colonoscopy, hence assistance with transportation home and recovery time post-colonoscopy is required.²⁵ Abnormal findings identified by flexible sigmoidoscopy or CT colonography screening require additional work-up by colonoscopy.

Additional Tools and Resources

The National Cancer Institute and the Centers for Disease Control and Prevention have developed patient and clinician guides on screening for colorectal cancer:

• Colorectal Cancer Screening (PDQ®)—Patient Version: https://www.cancer.gov/types/colorectal/patient/colorectal-screening-pdq
• Colorectal Cancer Screening (PDQ®)—Health Professional Version: https://www.cancer.gov/types/colorectal/hp/colorectal-screening-pdq
• Colorectal Cancer Screening Tests: https://www.cdc.gov/cancer/colorectal/basic_info/screening/tests.htm

The Community Preventive Services Task Force (CPSTF) has also issued recommendations on interventions to increase colorectal cancer screening:

• CPSTF Findings for Cancer Prevention and Control: https://www.thecommunityguide.org/content/task-force-findings-cancer-prevention-and-control

Other Related USPSTF Recommendations

The USPSTF has made a recommendation on aspirin use for the primary prevention of cardiovascular disease and colorectal cancer in average-risk adults (available at www.uspreventiveservicestaskforce.org).²⁶

When final, this recommendation will replace the 2016 USPSTF recommendation on screening for colorectal cancer. In 2016, the USPSTF recommended screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A grade recommendation). In addition, the USPSTF concluded that 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 (C grade recommendation), and that screening should be discontinued after age 85 years.

In the current draft recommendation, while continuing to recommend colorectal cancer screening in adults ages 50 to 75 years (A grade recommendation), the USPSTF now recommends offering screening at age 45 years (B grade recommendation). As it did in 2016, the USPSTF continues to conclude that screening in adults ages 76 to 85 years should be an individual one (C grade recommendation) and screening should be discontinued after age 85 years.

Scope of Review

To update its 2016 recommendation, the USPSTF commissioned a systematic review¹⁰ to evaluate the benefits and harms of screening for colorectal cancer in adults age 40 years and older. As in 2016, the USPSTF reviewed the evidence on: 1) the effectiveness and comparative effectiveness of screening strategies to reduce colorectal cancer incidence, colorectal cancer mortality, or both; 2) the accuracy of various screening tests to detect colorectal cancer, advanced adenomas, or adenomatous polyps based on size; and 3) the serious harms of different screening tests. The review also examined whether these findings varied by age, sex, or race/ethnicity.

In addition, as in 2016, the USPSTF commissioned a report from the CISNET Colorectal Cancer Working Group⁹ to provide information from comparative modeling on how estimated life-years gained, colorectal cancer cases averted, and colorectal cancer deaths averted vary by different starting and stopping ages for various screening strategies. Analyses with elevated risk scenarios to reflect recent population trends in colorectal cancer incidence⁴ and analyses by race were newly included in the current modeling performed by CISNET.⁹ 

Accuracy of Screening Tests

The USPSTF focused on reviewing evidence that reported accuracy of screening tests compared to colonoscopy as the reference standard. Colonoscopy accuracy is reported with a reference standard of either repeat colonoscopy or CT colonography–enhanced colonoscopy. The following accuracy results reflect accuracy after only a single application of the test rather than a program of repeated screenings. 

Stool-Based Tests

Evidence on accuracy of HSgFOBT to detect colorectal cancer and advanced adenomas compared to a colonoscopy reference standard was reported in two trials (n=3,503).¹⁰ Reported sensitivities to detect colorectal cancer range from 0.50 to 0.75 (95% confidence interval [CI], 0.09 to 1.0) and reported specificities range from 0.96 to 0.98 (95% CI, 0.95 to 0.99). Sensitivity for detecting advanced adenomas was lower, ranging from 0.06 to 0.17 (95% CI, 0.02 to 0.23), while specificity was similar (0.96 to 0.99 [95% CI, 0.96 to 0.99], respectively).¹⁰ A larger evidence base was available on the accuracy of FIT, with the most evidence being available on the OC Sensor family of FITs (k=9, n=34,352).¹⁰ Using the threshold recommended by the manufacturer (20 μg Hb/g of stool), the pooled sensitivity and specificity for detection of colorectal cancer were 0.74 (95% CI, 0.64 to 0.83) and 0.94 (95% CI, 0.93 to 0.96), respectively. Similar to HSgFOBT, sensitivity for detecting advanced adenomas was lower while specificity was similar; pooled sensitivity was 0.23 (95% CI, 0.20 to 0.25) and pooled specificity was 0.96 (95% CI, 0.95 to 0.97).¹⁰ Accuracy of nine other types of FIT were similar but were generally reported only in a single study. In four studies (n=12,424) reporting the accuracy of sDNA-FIT,¹⁰ pooled sensitivity for colorectal cancer detection was 0.93 (95% CI, 0.87 to 1.0) and pooled specificity was 0.84 (95% CI, 0.84 to 0.86), with a lower pooled sensitivity for detecting advanced adenomas (0.43 [95% CI, 0.40 to 0.46]) but higher pooled specificity (0.89 [95% CI, 0.86 to 0.92]).¹⁰ Ten of the accuracy studies on FIT also reported results by age strata and generally found no significant difference. Of the four studies that looked specifically at adults ages 40 to 49 years, no difference in the accuracy of FIT performance in adults ages 40 to 49 years compared to performance in older adults was reported in four studies. Two studies suggested lower specificity for colorectal cancer detection in adults age 70 years and older; a single study on sDNA-FIT suggested decreasing specificity with increasing age.¹⁰ 

Direct Visualization Tests

Colonoscopy was evaluated in four studies (n=4,821) on accuracy, with two studies (n=1,685) determining missed cases of colorectal cancer by follow-up CT colonography–enhanced colonoscopy or CT colonography and repeat colonoscopy for discrepant findings.¹⁰ All cases of colorectal cancer were detected by initial colonoscopy in two studies (n=3,136). In all four studies, sensitivity for detection of adenomas measuring 10 mm or larger ranged from 0.89 (95% CI, 0.78 to 0.96) to 0.95 (95% CI, 0.74 to 0.99); specificity was reported in a single study as 0.89 (95% CI, 0.86 to 0.91).¹⁰ Two of the studies on colonoscopy accuracy included patients younger than age 50 years, although results in this age group were not reported separately. Seven studies (n=5,328) reported on accuracy of CT colonography.¹⁰ The studies were heterogeneous in study design, population, imaging technique, and reader experience or protocol. Sensitivity for colorectal cancer detection was reported in six of the studies and ranged from 0.86 to 1.0 (95% CI range, 0.21 to 1.0); specificity was not reported. Sensitivity for detection of adenomas measuring 10 mm or larger ranged from 0.67 (95% CI, 0.45 to 0.84) to 0.94 (95% CI, 0.84 to 0.98) and specificity ranged from 0.86 (95% CI, 0.85 to 0.87) to 0.98 (95% CI, 0.96 to 0.99). One study reported CT colonography accuracy by age and suggested sensitivity was lower in adults age 65 years and older; however, this finding was not statistically significant. The USPSTF did not identify any studies that reported on the accuracy of flexible sigmoidoscopy using colonoscopy as the reference standard. 

Benefits of Early Detection and Treatment

Direct evidence on the benefits of colorectal cancer screening to decrease colorectal cancer mortality are available from randomized, controlled trials (RCTs) on gFOBT and flexible sigmoidoscopy as well as cohort studies on FIT and colonoscopy. Pooled results from four RCTs (n=458,002) on flexible sigmoidoscopy compared to no screening show a significant decrease in colorectal cancer mortality (mortality rate ratio, 0.74 [95% CI, 0.68 to 0.80]) over 11 to 17 years of followup.¹⁰ Most studies reported outcomes after a single round of screening, although the one trial conducted in the United States, the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial,²⁷ evaluated two rounds of screening. Decreased mortality with flexible sigmoidoscopy screening was consistently reported across the four trials. None of the trials included persons younger than age 50 years. Trials that report on colorectal cancer outcomes with HSgFOBT screening are currently lacking, although several older trials report decreased colorectal cancer mortality with Hemoccult II screening (an older gFOBT no longer commonly used). After two to nine rounds of biennial gFOBT screening, colorectal cancer mortality was found to be lower at 11 to 30 years of followup (relative risk range, 0.78 [95% CI, 0.65 to 0.93] to 0.91 [95% CI, 0.84 to 0.98]). Participants younger than age 50 years were included in three trials, although results for that age group were not reported separately.

Two prospective cohort studies (n=436,927) in U.S.-based populations reported on colorectal cancer outcomes after colonoscopy screening.¹⁰ One study among health professionals found that after 24 years of followup, colorectal mortality was lower in persons who reported receiving at least one colonoscopy (adjusted hazard ratio, 0.32 [95% CI, 0.24 to 0.45]),²⁸ although findings were no longer significant for adults with a first-degree relative with colorectal cancer. This study included persons younger than age 50 years, although results for this age group were not reported separately. Another cohort study in Medicare beneficiaries reported that the risk of colorectal cancer was significantly lower in adults ages 70 to 74 years (but not ages 75 to 79 years) 8 years after receiving a screening colonoscopy (standardized risk, 0.42% [95% CI, 0.24 to 0.63]). One large, prospective cohort study (n=5,417,699) from Taiwan reported on colorectal cancer mortality after introduction of a nationwide screening program with FIT in adults ages 50 to 69 years.²⁹ After one to three rounds of biennial FIT screening, lower colorectal cancer screening mortality was found at 6 years of followup (adjusted relative risk, 0.90 [95% CI, 0.84 to 0.95]).

The CISNET modeling study commissioned for this review estimated the number of life-years gained, colorectal cancer cases and deaths averted, lifetime colonoscopies required (as a proxy measure for the burden of screening), and resulting harms from colonoscopy (i.e., gastrointestinal and cardiovascular events) for various screening strategies. These strategies varied the screening modality, the age at which to start and stop screening, and the frequency of screening.⁹ In these analyses, the USPSTF focused on findings from models that assumed an elevated population risk to better capture the currently observed epidemiologic trend of increasing incidence in adults younger than age 50 years, which is thought to reflect cohort effects, with younger birth cohorts at greater risk for colorectal cancer than older cohorts.^4,9 The USPSTF focused on life-years gained as the primary measure of the benefit of screening. Given this elevated population risk assumption, as well as assuming 100% adherence, the USPSTF determined that beginning screening at age 45 years and continuing to the age of 75 years, for the following screening strategies, yielded a reasonable balance of benefits (life-years gained) and burdens or harms (number of colonoscopies): annual FIT or sDNA-FIT; CT colonography or flexible sigmoidoscopy every 5 years; colonoscopy every 10 years; or flexible sigmoidoscopy every 10 years with annual FIT (see Figure). Screening with sDNA-FIT annually results in additional colonoscopy burden than annual FIT screening (approximately 850 more subsequent diagnostic and surveillance colonoscopies needed per 1,000 adults screened with annual sDNA-FIT).⁹ Performing sDNA-FIT every 3 years or HSgFOBT annually (also included in the Figure) did not provide an efficient balance of the benefits (life-years gained) vs. the harms and burdens (i.e., lifetime number of colonoscopies), compared to other options for stool-based screening.⁹ Additionally, there is greater uncertainty in the model predictions for HSgFOBT strategies, given the underlying uncertainty on the sensitivity and specificity of HSgFOBT to detect adenomas and colorectal cancer.^9,10

Based on averaging estimates across the three models, if screening were performed from ages 45 to 75 years with one of the USPSTF recommended strategies, 286 to 337 life-years would be gained, 42 to 61 cases of colorectal cancer would be averted, and 24 to 28 colorectal cancer deaths would be averted, per 1,000 adults screened, depending on the specific strategy used (see Figure).⁹ This finding translates to 104 to 123 days of life gained per person screened. Lowering the starting age of screening from age 50 years to age 45 years results in approximately 2 to 3 cases of colorectal cancer being averted, 1 additional colorectal cancer death averted, and 22 to 27 additional life-years gained per 1,000 adults (i.e., 8 to 10 additional days of life gained per person screened)⁹ (see Figure). 

Harms of Screening and Treatment

No studies reported on harms from stool-based tests.¹⁰ The primary harms from stool-based screening tests are thought to come from false-positive and false-negative results, and from harms of diagnostic work-up of positive screening results, such as colonoscopy. Serious harms from diagnostic colonoscopy to follow up positive screening results are estimated to be 17.5 serious bleeds (95% CI, 7.6 to 27.5) and 5.7 perforations (95% CI, 2.8 to 8.7) per 10,000 colonoscopies (k=11, n=78,793).¹⁰

Harms from screening colonoscopy have been reported in 67 observational studies (n=27,746,669).¹⁰ Rates of serious bleeds and perforations are lower with screening colonoscopy than with diagnostic colonoscopy (presumably due to fewer biopsies and adenoma removals) to follow up positive stool-based screening tests, with 14.6 major bleeds per 10,000 colonoscopies (95% CI, 9.4 to 19.9) and 3.1 perforations per 10,000 colonoscopies (95% CI, 2.3 to 4.0).¹⁰ If sedation is used during colonoscopy, cardiopulmonary events may rarely occur (k=3, n=34,478); the precise frequency of occurrence is not known. Other serious reported harms include infection and other gastrointestinal events (besides bleeds and perforation). Twenty-one studies included persons younger than age 50 years and 19 studies reported on differences in harms with age. Overall findings indicated increasing risk of bleeding and perforation with increasing age. Bowel preparation for colonoscopy, flexible sigmoidoscopy, and CT colonography 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.

Harms from flexible sigmoidoscopy were reported in 18 observational studies (n=395,077).¹⁰ Rate of serious harms were 0.5 bleeds per 10,000 sigmoidoscopies (k=11; n=179,854; 95% CI, 0 to 1.3) and 0.2 perforations per 10,000 sigmoidoscopies (k=11; n=359,679; 95% CI, 0.1 to 0.4). No studies included persons younger than age 50 years and no subgroup analyses on harms by age were reported. Rates of harms from diagnostic colonoscopy following an abnormal flexible sigmoidoscopy include 20.7 major bleeds per 10,000 colonoscopies (k=4; n=5,790; 95% CI, 8.2 to 33.2) and 12.0 perforations per 10,000 colonoscopies (k=4; n=23,022; 95% CI, 7.5 to 16.5).

Serious harms from CT colonography are uncommon (k=19, n=90,133), and the reported radiation dose for CT colonography ranges from 0.8 to 5.3 mSv (compared to an average, annual background radiation dose of 3.0 mSv per person in the United States).¹⁰ Extracolonic findings on CT colonography are common. Based on 27 studies that included 48,235 participants, 1.3% to 11.4% of examinations identified extracolonic findings that required work-up.¹⁰ Three percent or fewer individuals with extracolonic findings required definitive medical or surgical treatment for an incidental finding. A few studies suggest that extracolonic findings may be more common in older age groups. Long-term clinical followup of extracolonic findings was reported in few studies, making it difficult to know whether it represents a benefit or harm of CT colonography.

Based on the available empiric evidence,¹⁰ harms from colonoscopy (either a screening colonoscopy, a diagnostic colonoscopy followup of a positive screening result from other methods, or surveillance colonoscopy in persons whose adenomas have previously been detected) were considered to be the main source of colorectal cancer screening harms in the CISNET modeling study.⁹ Thus harms were quantified as the lifetime number of colonoscopy complications associated with screening and the lifetime number of colonoscopies was used as a proxy for the burden of screening. Based on averaging estimates across the three models, if screening were performed from ages 45 to 75 years with one of the USPSTF recommended strategies, 1,535 to 4,248 colonoscopy procedures and 10 to 16 colonoscopy complications would be expected over the lifetime of 1,000 screened adults (i.e., 1.5 to 4.2 colonoscopies per person over the lifetime and complications occurring in 1 in every 63 to 102 adults screened from ages 45 to 75 years).⁹

Although the benefits of screening for colorectal cancer are well established, the following important evidence gaps that need to be addressed by additional research persist.

• Randomized trials that compare the effectiveness of different colorectal cancer screening strategies to reduce colorectal cancer mortality are needed.
• Studies are needed on screening effectiveness and accuracy of screening tests in Black adults and adults younger than age 50 years.
• More research is needed to understand the factors that contribute to increased colorectal cancer incidence and mortality in Black adults, such as access and availability of care and characteristics of systems providing health care.
• More studies evaluating the direct effectiveness of screening with sDNA-FIT on colorectal cancer mortality outcomes and studies that report outcomes of patients who receive abnormal sDNA-FIT results but negative colonoscopies are needed.
• More studies evaluating the direct effectiveness of screening with CT colonography on colorectal cancer mortality are needed, as well as more studies that report on long-term consequences of identifying extracolonic findings on colorectal cancer screening.
• More research is needed to understand the uptake and adherence to individual screening tests and the effect adherence has on the overall benefits of a screening program. Similarly, more research is needed on the accuracy and effectiveness of emerging screening technologies such as serum- and urine-based colorectal cancer screening tests and capsule endoscopy tests to potentially improve acceptance and adherence to colorectal cancer screening, if found to be accurate and effective.

Many organizations have issued guidelines on screening for colorectal cancer. There is a general consensus that average-risk adults ages 50 to 75 years should be screened. The American Academy of Family Physicians (AAFP),³⁰ American College of Physicians (ACP),³¹ the American Cancer Society (ACS),³² and the U.S. Multi-Society Task Force (which includes the American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy)²⁰ all recommend routine colorectal cancer screening in this age group, although specific recommended tests and frequency of screening may vary. Generally, guidelines agree that screening should either be individualized in older adults ages 76 to 85 years (ACS and AAFP) or stopped altogether (ACP and U.S. Multi-Society Task Force), with clear consensus that screening should stop after age 85 years. Currently, where recommendations and guidelines vary is the age to initiate screening. The U.S. Multi-Society Task Force recommends beginning screening at age 45 years in Black adults (weak recommendation) and screening at age 40 years (or 10 years before the age at diagnosis of a family member, whichever is earlier) in persons with a family history for colorectal cancer. ACS issued a qualified recommendation to begin screening at age 45 years in all adults. AAFP’s recommendations do not address screening before age 50 years.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.
2. Surveillance, Epidemiology, and End Results. Cancer Stat Facts: Colorectal Cancer. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed October 5, 2020.
3. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177-193.
4. Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017;109(8):djw322.
5. Centers for Disease Control and Prevention. Quick Facts: Colorectal Cancer Screening in U.S. Behavioral Risk Factor Surveillance System - 2016. https://www.cdc.gov/cancer/colorectal/pdf/QuickFacts-BRFSS-2016-CRC-Screening-508.pdf. Accessed October 5, 2020.
6. U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Procedure Manual. https://uspreventiveservicestaskforce.org/uspstf/procedure-manual. Accessed October 5, 2020.
7. Lowery JT, Ahnen DJ, Schroy PC 3rd, et al. Understanding the contribution of family history to colorectal cancer risk and its clinical implications: a state-of-the-science review. Cancer. 2016;122(17):2633-2645.
8. Centers for Disease Control and Prevention. Colorectal Cancer Screening Tests. https://www.cdc.gov/cancer/colorectal/basic_info/screening/tests.htm. Accessed October 5, 2020.
9. Knudsen AB, Rutter CM, Peterse EF, et al. Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force. AHRQ Publication No. 20-05271-EF-2. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
10. Lin JS, Perdue LA, Henrikson NB, Bean SI, Blasi PR. Screening for Colorectal Cancer: An Evidence Update for the U.S. Preventive Servcies Task Force. Evidence Synthesis No. 202. AHRQ Publication No. 20-05271-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
11. Surveillance, Epidemiology, and End Results. SEER*Stat Database: Incidence - SEER 9 Regs Research Data With Delay-Adjustment, Malignant Only, Nov 2018 Sub (1975-2016) <Katrina/Rita Population Adjustment> - Linked to County Attributes - Total U.S., 1969-2017 Counties. Released April 2019, based on the November 2018 submission.
12. Lansdorp-Vogelaar I, Gulati R, Mariotto AB, et al. Personalizing age of cancer screening cessation based on comorbid conditions: model estimates of harms and benefits. Ann Intern Med. 2014;161(2):104-12.
13. National Cancer Institute. PDQ Colon Cancer Treatment–Health Professional Version. https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq. Accessed October 6, 2020.
14. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2017. https://seer.cancer.gov/csr/1975_2017/. Acessed October 5, 2020.
15. Doubeni CA, Rustgi A. Racial disparities in colorectal cancer survival: is elimination of variation in care the cure? J Natl Cancer Inst. 2015;107(10):djv229.
16. Rutter C, Knudsen A, Lin J, Bouskill K. Black and white differences in colorectal cancer screening and screening outcomes: a narrative review. Cancer Epidemiol Biomarkers Prev. 2019; in press.
17. Virostko J, Capasso A, Yankeelov TE, Goodgame B. Recent trends in the age at diagnosis of colorectal cancer in the US National Cancer Data Base, 2004-2015. Cancer. 2019;125(21):3828-3835.
18. Rutter CM, Johnson EA, Feuer EJ, et al. Secular trends in colon and rectal cancer relative survival. J Natl Cancer Inst. 2013;105(23):1806-1813.
19. Arias E, Xu J. United States Life Tables, 2017. Hyattsville, MD: National Center for Health Statistics; 2019.
20. Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2017;86(1):18-33.
21. U.S. National Library of Medicine. Fecal occult blood test (FOBT). https://medlineplus.gov/lab-tests/fecal-occult-blood-test-fobt/. Accessed October 6, 2020.
22. U.S. National Library of Medicine. Fecal immunochemical test (FIT). https://medlineplus.gov/ency/patientinstructions/000704.htm. Accessed October 6, 2020.
23. U.S. National Library of Medicine. Cologuard. https://medlineplus.gov/ency/article/007747.htm. Accessed October 6, 2020.
24. National Institute of Diabetes and Digestive and Kidney Diseases. Virtual Colonoscopy. https://www.niddk.nih.gov/health-information/diagnostic-tests/virtual-colonoscopy. Accessed October 5, 2020.
25. National Institute of Diabetes and Digestive and Kidney Diseases. Colonoscopy. https://www.niddk.nih.gov/health-information/diagnostic-tests/colonoscopy. Accessed October 5, 2020.
26. U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164(12):836-845.
27. Miller EA, Pinsky PF, Schoen RE, Prorok PC, Church TR. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: long-term follow-up of the randomised US PLCO cancer screening trial. Lancet Gastroenterol Hepatol. 2019;4(2):101-110.
28. Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. New Engl J Med. 2013;369(12):1095-1105.
29. Chiu HM, Chen SL, Yen AM, et al. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Cancer. 2015;121(18):3221-3229.
30. American Academy of Family Physicians. Clinical Preventive Service Recommendation: Colorectal Cancer Screening, Adults. https://www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/colorectal-cancer-adults.html. Accessed October 5, 2020.
31. Qaseem A, Crandall CJ, Mustafa RA, Hicks LA, Wilt TJ; Clinical Guidelines Committee of the American College of Physicians. Screening for colorectal cancer in asymptomatic average-risk adults: a guidance statement from the American College of Physicians. Ann Intern Med. 2019;171(9):643-654.
32. Wolf AM, Fontham ET, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281.

* Applies to persons with negative findings (including hyperplastic polyps) and is not intended for persons in surveillance programs. Evidence of efficacy is not informative of screening frequency, with the exception of gFOBT and flexible sigmoidoscopy alone.
^† Suggested by manufacturer. 

Abbreviations: CRC=colorectal cancer; CT=computed tomography; FIT=fecal immunochemical test; HSgFOBT=high-sensitivity guaiac-based fecal occult blood test; RCT=randomized controlled trial; sDNA-FIT=stool DNA test plus fecal immunochemical test.

FIT indicates fecal immunochemical test with a cutoff for positivity of 20 μg of hemoglobin per g of feces; HSgFOBT, high-sensitivity fecal occult blood test; sDNA-FIT, multi-target stool DNA test (stool DNA test with a fecal immunochemical test).
* Outcomes are expressed per 1,000 40-year-olds who start screening at age 45 or at age 50.
† Average estimate across the three CISNET colorectal cancer models. See modeling report for additional details and model-specific estimates.
‡ Due to imprecision in sensitivity and specificity, there is considerable uncertainty in model predictions for HSgFOBT strategies. See modeling report for more information.
§ Compared to other options for stool-based screening, these strategies do not provide an efficient balance of the benefits (life-years gained) vs. harms and burden (i.e., lifetime no. of colonoscopies) of screening. See modeling report for more information.
‖ Other tests include FIT, HSgFOBT, sDNA-FIT, computed tomographic (CT) colonography, and flexible sigmoidoscopy (SIG).