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医療専門家向け Colorectal Cancer Screening (PDQ®)

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about colorectal cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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Summary of Evidence

Note: Separate PDQ summaries on Colorectal Cancer Prevention; Colon Cancer Treatment; and Rectal Cancer Treatment are also available.

Evidence of Benefit Associated With Colorectal Cancer Screening

Based on solid evidence, screening for colorectal cancer (CRC) reduces CRC mortality. In addition, there is solid evidence that some CRC screening modalities also reduce CRC incidence. A meta-analysis of flexible sigmoidoscopy randomized controlled trials found that screening with sigmoidoscopy reduces all-cause mortality.

Table 1. Effect of Screening Intervention on Reducing Incidence and Mortality from Colorectal Cancera
Screening Intervention Study Design Internal Validity Consistency Magnitude of Effect on CRC Incidence Magnitude of Effect on CRC Mortality External Validity
CRC = colorectal cancer; FIT = fecal immunochemical testing; RCT = randomized controlled trial.
aThere are no data from RCTs on the effect of other screening interventions (i.e., barium enema, computed tomographic colonography, and stool DNA mutation tests) on mortality from CRC. There are also no published results of RCTs of FIT with mortality as an endpoint.
bFIT is being compared with colonoscopy in two RCTs in Europe (NCT00906997 [Spain] and NCT02078804 [Sweden]), one in the United States (NCT01239082), and one in China (ChiCTR1900025257).[ 1 ][ 2 ] The trial in Sweden compares colonoscopy with FIT and population controls. Mortality results are not available, and may be limited for FIT because of the absence of no-screening comparison groups in several trials. Current guideline recommendations have depended on FIT using the same mechanism as guaiac tests, the most sensitive of which had similar sensitivity to FIT [ 3 ] and showed significant reductions in both mortality and incidence of CRC.[ 3 ][ 4 ][ 5 ]
cThe NordICC trial compares a colonoscopy group with a usual-care control group [NCT00883792].
Fecal Occult Blood Test (guaiac-based) RCTs [ 6 ] Good Good Likely small to none 15%–33% Fair
Fecal Occult Blood Test (fecal immunochemical-based: FIT) RCTs ongoingb Fair Fair Fair Fair Fair
Sigmoidoscopy RCTs Good Good 20%–25% 22%–31%; 13%–50% for distal colon Fair
Digital Rectal Exam Case-control studies Fair Good No effect No effect Poor
Colonoscopy No RCTs (RCTs in-progress)c; case-control studies; observational cohort studies that use historical/other controls Poor Poor About 60%–70% for left colon; uncertain for right colon About 60%–70% for distal colon; uncertain for right colon Fair
参考文献
  1. Quintero E, Castells A, Bujanda L, et al.: Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 366 (8): 697-706, 2012.[PUBMED Abstract]
  2. Dominitz JA, Robertson DJ, Ahnen DJ, et al.: Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design. Am J Gastroenterol 112 (11): 1736-1746, 2017.[PUBMED Abstract]
  3. Church TR, Ederer F, Mandel JS: Fecal occult blood screening in the Minnesota study: sensitivity of the screening test. J Natl Cancer Inst 89 (19): 1440-8, 1997.[PUBMED Abstract]
  4. Mandel JS, Church TR, Bond JH, et al.: The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 343 (22): 1603-7, 2000.[PUBMED Abstract]
  5. Mandel JS, Bond JH, Church TR, et al.: Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 328 (19): 1365-71, 1993.[PUBMED Abstract]
  6. Hewitson P, Glasziou P, Watson E, et al.: Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol 103 (6): 1541-9, 2008.[PUBMED Abstract]
Description of the Evidence

Background

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide [ 1 ] and the third leading cause of cancer deaths in the United States.[ 2 ] It is estimated that there will be 149,500 new cases diagnosed in the United States in 2021 and 52,980 deaths due to this disease. From 2013 to 2017, CRC incidence declined by about 1% per year. From 2014 to 2018, mortality from CRC declined by about 2% per year.[ 2 ] Incidence is higher in men than in women. The incidence rates range from 40.7 per 100,000 per year in Hispanic men to 51.3 per 100,000 per year in African American men. In women, the incidence rates range from 29.8 per 100,000 per year in Hispanic women to 38.2 per 100,000 per year in African American women. The age-adjusted mortality rates are 16.6 per 100,000 per year in men and 11.8 per 100,000 per year in women. About 4.2% of Americans are expected to develop the disease within their lifetime, and the lifetime risk of dying from CRC is 1.7%.[ 3 ] Age-specific incidence and mortality rates show that most cases are diagnosed after age 54 years and 78% of cases occur in patients aged 55 years and older; about 15% of CRC cases occur in patients aged 45 to 54 years.[ 3 ][ 4 ][ 5 ]

Long-term trends in CRC were addressed in an analysis of national data for the period 1975 to 2010.[ 6 ] Incidence increased for men from 1975 to 1985, but there were marked declines from 1985 to 1995 for both men and women followed by a nonsignificant increase from 1995 to 1998, then marked declines from 1998 to 2010. Death rates from CRC have declined since 1984 in both men and women, with an accelerated rate of decline since 2002 for men and since 2001 for women. From 1997 to 2010, CRC incidence declined for all racial/ethnic groups. The fastest annual rate of decline occurred in men and women aged 65 years or older. There was a trend of increasing short-term incidence rates for individuals younger than 50 years in most population subgroups. Incidence rates of distal colon and rectal cancers decreased in men and women for all ages combined. Incidence rates of proximal colon cancer also decreased in men and women for all race/ethnicities combined.

Risk Factors

Age and family history

The main risk factor for CRC is increasing age; 90% of all CRCs are diagnosed after age 50 years. History of CRC in a first-degree relative, especially occurring before age 55 years, approximately doubles the risk.

Adenomas

The presence of adenomas (lesions considered to be the histologic [neoplastic but nonmalignant] precursors of CRC) is another major risk factor. Adenomas are extremely common; for example, in individuals older than 50 years, the prevalence of adenomas is approximately 30%, but can be as high as 50% when high-definition endoscopes, which can detect 1 mm to 2 mm adenomas, are used.[ 7 ][ 8 ] Adenomas confer risk as they may themselves evolve into CRC. Additionally, even after their removal, an individual who has had an adenoma (particularly, if it has characteristics of high risk, on the basis of size and histology) may indicate future risk of CRC. Managing adenomas and risk is challenging because adenomas are prevalent as people age, but most will never become CRC.

Understanding risk and risk management has been complicated by the intense focus on adenoma-detection rates in the last 15 years, which has caused increased detection of adenomas, especially very small ones (<0.5 cm). Risk factors for developing CRC are not completely understood, but generally include the following:

Increased future risk of CRC is indicated by a personal history of CRC or high-risk adenomas (i.e., large [>1 cm] tubular adenomas, sessile-serrated adenomas, or multiple adenomas). Follow-up of individuals with these adenomas after they have undergone screening is considered surveillance and not screening.[ 9 ]

The term serrated polyp is currently used to include hyperplastic polyps, sessile-serrated adenomas, traditional-serrated adenomas, and mixed-serrated polyps.[ 10 ][ 11 ] The clinical significance of these lesions is uncertain because the natural history of any polypoid lesion is difficult to learn. However, the histologic and molecular characteristics of some serrated lesions suggest possibly important malignant potential (e.g., mutations in the BRAF gene may be an early step toward carcinogenesis in serrated polyps).[ 12 ]

Prevalence of adenomas and CRC in asymptomatic populations

In a colonoscopy study of 3,121 predominantly male U.S. veterans (mean age, 63 years), advanced neoplasia (defined as an adenoma that was ≥10.0 mm in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer) was identified in 10.5% of the individuals.[ 8 ] Among patients with no adenomas distal to the splenic flexure, 2.7% had advanced proximal neoplasia. Patients with large adenomas (≥10.0 mm) or small adenomas (<10.0 mm) in the distal colon were more likely to have advanced proximal neoplasia (odds ratio [OR], 3.4; 90% confidence interval [CI], 1.8–6.5) than were patients with no distal adenomas (OR, 2.6; 90% CI, 1.7–4.1). One-half of those with advanced proximal neoplasia had no distal adenomas. In a study of 1,994 adults aged 50 years or older who underwent colonoscopy screening as part of a program sponsored by an employer, 5.6% of adults had advanced neoplasms.[ 7 ] Forty-six percent of those with advanced proximal neoplasms had no distal polyps (hyperplastic or adenomatous). If colonoscopy screening had been performed only in patients with distal polyps, about one-half of the cases of advanced proximal neoplasia would not have been detected.

Analysis of data from a colonoscopy-based screening program in Warsaw, Poland, demonstrated higher rates of advanced neoplasia in men than in women. Of the 43,042 participants aged 50 to 66 years, advanced neoplasia was detected in 5.9% of participants (5.7% in women with a family history of CRC, 4.3% in women without a family history of CRC, 12.2% in men with a family history of CRC, and 8.0% in men without a family history of CRC).

In a cohort study within the Polish Colonoscopy Screening Program, nearly 166,000 participants were followed for up to 17 years after a single negative colonoscopy. Standardized incidence ratios that compared the participants to the general population were 0.32 (95% CI, 0.29–0.35) for low-quality colonoscopy (LQC) and 0.16 (95% CI, 0.13–0.20) for high-quality colonoscopy (HQC). Standardized mortality ratios were 0.22 (95% CI, 0.18–0.25) for LQC and 0.10 (95% CI, 0.06–0.14) for HQC. Colonoscopy, especially HQC, was predictive of low CRC incidence and mortality for at least 10 years after a negative exam, suggesting that the currently recommended 10-year interval for screening is safe and could potentially be extended.[ 13 ]

参考文献
  1. Ferlay J, Soerjomataram I, Ervik M, et al.: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. Lyon, France: International Agency for Research on Cancer, 2013. IARC CancerBase No. 11. Available online. Last accessed January 8, 2021.[PUBMED Abstract]
  2. American Cancer Society: Cancer Facts and Figures 2021. American Cancer Society, 2021. Available online. Last accessed June 02, 2021.[PUBMED Abstract]
  3. Howlader N, Noone AM, Krapcho M, et al.: SEER Cancer Statistics Review (CSR) 1975-2017. Bethesda, Md: National Cancer Institute, 2020. Available online. Last accessed March 17, 2021.[PUBMED Abstract]
  4. National Cancer Institute: SEER Stat Fact Sheets: Colorectal Cancer. Bethesda, Md: National Institutes of Health. Available online. Last accessed January 8, 2021.[PUBMED Abstract]
  5. Imperiale TF, Wagner DR, Lin CY, et al.: Results of screening colonoscopy among persons 40 to 49 years of age. N Engl J Med 346 (23): 1781-5, 2002.[PUBMED Abstract]
  6. Edwards BK, Noone AM, Mariotto AB, et al.: Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120 (9): 1290-314, 2014.[PUBMED Abstract]
  7. Imperiale TF, Wagner DR, Lin CY, et al.: Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med 343 (3): 169-74, 2000.[PUBMED Abstract]
  8. Lieberman DA, Weiss DG, Bond JH, et al.: Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 343 (3): 162-8, 2000.[PUBMED Abstract]
  9. Lieberman DA, Rex DK, Winawer SJ, et al.: Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 143 (3): 844-57, 2012.[PUBMED Abstract]
  10. Kahi CJ, Hewett DG, Norton DL, et al.: Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy. Clin Gastroenterol Hepatol 9 (1): 42-6, 2011.[PUBMED Abstract]
  11. Snover DC, Batts KP: Serrated Colorectal Neoplasia. Surg Pathol Clin 3 (2): 207-40, 2010.[PUBMED Abstract]
  12. Snover DC, Jass JR, Fenoglio-Preiser C, et al.: Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol 124 (3): 380-91, 2005.[PUBMED Abstract]
  13. Pilonis ND, Bugajski M, Wieszczy P, et al.: Long-Term Colorectal Cancer Incidence and Mortality After a Single Negative Screening Colonoscopy. Ann Intern Med 173 (2): 81-91, 2020.[PUBMED Abstract]
Evidence of Benefit

Fecal Occult Blood Test (FOBT)

In FOBT testing, stool samples are collected and analyzed for the presence of small amounts of blood. The first generation of FOBTs used guaiac-based assays to detect blood, which are less sensitive and less specific than immunochemical-based testing. The now-classic randomized controlled trials (RCTs) that assessed colorectal cancer (CRC) mortality reduction all used guaiac-based testing. The finding of decreased CRC mortality provided a major foundation for recommendations to do CRC screening. The first-generation guaiac-based tests are being replaced with more sensitive and more specific immunochemical tests that have not yet been assessed in RCTs with a no-screening control group.

In this setting, the RCT evidence about guaiac-based testing is reviewed briefly here, with further discussion of how immunochemical FOBT (iFOBT or FIT) may provide improved sensitivity and specificity. Generally, if guaiac FOBT (gFOBT) is acceptable as a screening test (as shown in RCTs), then a strong case can be made for using a more sensitive and more specific test like FIT.

gFOBT collection details vary somewhat for different tests, but they typically involve collection of as many as three different specimens on 3 different days, with small amounts from one specimen smeared by a wooden stick on a card with two windows or otherwise placed in a specimen container.

The guaiac test identifies peroxidase-like activity that is characteristic of human and nonhuman hemoglobin. Thus, the test records blood from ingested meat, upper airway bleeding such as epistaxis, upper gastrointestinal (GI) bleeding, and colonic lesions.

A systematic review regarding evidence of benefit was conducted through the Cochrane Collaboration. It examined all CRC screening randomized trials that involved gFOBT testing done on more than one occasion. The combined results showed that trial participants allocated to screening had a 16% lower CRC mortality (relative risk [RR], 0.84; 95% confidence interval [CI], 0.78–0.90). There was no difference in all-cause mortality between the screened groups and the control groups (RR, 1.00; 95% CI, 0.99–1.02). The trials reported a low positive predictive value (PPV) for the FOBT test, suggesting that most positive tests were false positives. The PPV was 5.0% to 18.7% in the trials using nonrehydrated slides (Funen and Nottingham studies), and it was 0.9% to 6.1% in the trials using rehydrated slides (Goteborg and Minnesota studies). The report contained no discussion about contamination in the control arms of the trials and no information about treatment by disease stage.[ 1 ][ 2 ]

On initial (prevalence) examinations, 1% to 5% of unselected persons tested with gFOBT had positive test results. Of those who tested positive, approximately 2% to 10% had cancer and approximately 20% to 30% had adenomas,[ 3 ][ 4 ] depending on how the test was done. Data from RCTs of gFOBT testing are summarized in Table 2.

Four controlled clinical trials have been completed or are in progress to evaluate the efficacy of screening utilizing gFOBT. While more sensitive stool blood tests based on measuring human hemoglobin have been developed (and are discussed later in this summary), results about their performance in RCTs have not yet been reported. For gFOBT, the Swedish trial was a targeted study for individuals aged 60 to 64 years.[ 5 ] The English trial selected candidates from lists of family practitioners.[ 6 ] The Danish trial offered screening to a population aged 45 to 75 years who were randomly assigned to a control or study group.[ 7 ][ 8 ]

The Minnesota trial randomly assigned 46,551 men and women aged 50 to 80 years to one of three arms: colorectal cancer screening with gFOBT, rehydrated (with some small percentage of unrehydrated) FOBT every year (n = 15,570) or every 2 years (n = 15,587), or control (n = 15,394). This trial demonstrated that annual FOBT screening decreased mortality from CRC by 33% after 18 years of follow-up (RR, 0.67; 95% CI, 0.51–0.83, compared with the control group) and that biennial testing resulted in a 21% relative mortality reduction (RR, 0.79; 95% CI, 0.62–0.97).[ 9 ] Some part of the reduction may have been attributed to chance detection of cancer by colonoscopies; rehydration of guaiac test slides greatly increased positivity and consequently increased the number of colonoscopies performed.[ 10 ] Subsequent analyses by the Minnesota investigators using mathematical modeling suggested that for 75% to 84% of the patients, mortality reduction was achieved because of sensitive detection of CRCs by the test; chance detection played a modest role (16%–25% of the reduction).[ 11 ] Nearly 85% of patients with a positive test underwent diagnostic procedures that included colonoscopy or double-contrast barium enema plus flexible sigmoidoscopy (FS). After 18 years of follow-up, the incidence of CRC was reduced by 20% in the annually screened arm and 17% in the biennially screened arm. With follow-up through 30 years, there was a sustained reduction in CRC mortality of 32% in the annually screened arm (RR, 0.68; 95% CI, 0.56–0.82) and 22% in the biennially screened arm (RR, 0.78; 95% CI, 0.65–0.93). There was no reduction in all-cause mortality in either screened arm (RR, 1.00; 95% CI, 0.99–1.01 for the annually screened arm; and RR, 0.99; 95% CI, 0.98–1.01 for the biennially screened arm).[ 12 ] Important information that was not reported includes the treatment of CRC cases by stage by arm and the extent of CRC screening in each arm by FOBT, sigmoidoscopy, or colonoscopy after the completion of the trial protocol.[ 12 ][ 13 ]

The English trial allocated approximately 76,000 individuals to each arm. Those in the screened arm were offered nonrehydrated gFOBT testing every 2 years for three to six rounds from 1985 to 1995. At a median follow-up of 7.8 years, 60% completed at least one test, and 38% completed all tests. Cumulative incidence of CRC was similar in both arms, and the trial reported an RR reduction of 15% in CRC mortality (odds ratio [OR], 0.85; 95% CI, 0.74–0.98).[ 14 ] The serious complication rate of colonoscopy was 0.5%. There were five deaths within 30 days of surgery for screen-detected CRC or adenoma in a total of 75,253 individuals screened.[ 15 ] After a median follow-up of 11.8 years, no difference in CRC incidence between the intervention and control groups was observed. The disease-specific mortality rate ratio associated with screening was 0.87 (0.78–0.97; P = .01). The rate ratio for death from all causes was 1.00 (0.98–1.02; P = .79).[ 16 ] When the median follow-up was extended to 19.5 years, there was a 9% reduction in CRC mortality (RR, 0.91; 95% CI, 0.84–0.98) but no reduction in CRC incidence (RR, 0.97; 95% CI, 0.91–1.03), or death from all causes (RR, 1.00; 95% CI, 0.99–1.02).[ 17 ]

The Danish trial in Funen, Denmark, entered approximately 31,000 individuals into two arms, in which individuals in the screened arm were offered nonrehydrated gFOBT testing every 2 years for nine rounds over a 17-year period. Sixty-seven percent completed the first screen, and more than 90% of individuals invited to each subsequent screen underwent FOBT testing. This trial demonstrated an 18% reduction in CRC mortality at 10 years of follow-up,[ 18 ] 15% at 13 years of follow-up (RR, 0.85; 95% CI, 0.73–1.00),[ 19 ] and 11% at 17 years of follow-up (RR, 0.89; 95% CI, 0.78–1.01).[ 20 ] CRC incidence and overall mortality were virtually identical in both arms.

The Swedish trial in Goteborg enrolled all of its 68,308 citizens in the city who were born between 1918 and 1931 and were aged 60 to 64 years, and randomly assigned them to screening and control groups of nearly equal size. Participants in the control group were not contacted and were unaware they were part of the trial. Screening was offered at different frequencies to three different cohorts according to year of birth. Screening was done using the gFOBT Hemoccult-II test after dietary restriction. Nearly 92% of tests were rehydrated. Individuals with a positive test result were invited to an examination consisting of a case history, FS, and double-contrast barium enema. Follow-up ranged from 6 years 7 months to 19 years 5 months, depending on the date of enrollment. The primary endpoint was CRC-specific mortality. The overall screening compliance rate was 70%, and 47.2% of participants completed all screenings. Of the 2,180 participants with a positive test, 1,890 (86.7%) underwent a complete diagnostic evaluation with 104 cancers and 305 adenomas of at least 10 mm detected. In total, there were 721 CRCs (152 Dukes D, 184 Dukes C) in the screening group and 754 CRCs (161 Dukes D, 221 Dukes C) in the control group, with an incidence ratio of 0.96 (95% CI, 0.86–1.06). Deaths from CRC were 252 in the screening group and 300 in the control group, with a mortality ratio of 0.84 (95% CI, 0.71–0.99). This CRC mortality difference emerged after 9 years of follow-up. Deaths from all causes were very similar in the two groups, with a mortality ratio of 1.02 (95% CI, 0.99–1.06).[ 5 ]

Stage distribution

All trials have shown a more favorable stage distribution in the screened population than in controls (refer to Table 2). Data from the Danish trial indicated that while the cumulative incidence of CRC was similar in the screened and control groups, a higher percentage of CRCs and adenomas were Dukes A and Dukes B lesions in the screened group.[ 18 ] A meta-analysis of all previously reported randomized trials using biennial FOBT showed no overall mortality reduction by gFOBT screening (RR, 1.002; 95% CI, 0.989–1.085). The RR of CRC death in the gFOBT arm was 0.87 (95% CI, 0.8–0.95), and the RR of non–CRC death in the gFOBT group was 1.02 (95% CI, 1.00–1.04; P = .015).[ 21 ]

Mathematical modeling

Mathematical models have been constructed to extrapolate the results of screening trials and screening programs for benefit of the general population in community health care delivery settings. These models project that using currently available screening methodology can reduce CRC mortality or increase life expectancy.[ 22 ]

Table 2. Randomized Controlled Screening Trials to Assess Outcome: Guaiac-Based Fecal Occult Blood Testing
Site Population Size Positivity Rate (%) % Cancers Localized Testing Interval CRC Mortality Relative Risk (95% CI) CRC Incidence RR (95% CI)
CI = confidence interval; CRC = colorectal cancer; RR = risk ratio.
a% Localized = T1–3 N0 M0.
  Screened Control  
Minnesota [ 9 ][ 23 ] 48,000 Unrehydrated: 2.4% 59 53 Annual 0.67 (0.51–0.83) 0.80 (0.70–0.90)
  Rehydrated: 9.8%     Biennial 0.79 (0.62–0.97) 0.83 (0.73–0.94)
United Kingdom [ 14 ] 150,000 Unrehydrated: 2.1% 52 44 Biennial 0.85 (0.74–0.98) 1.04 (0.95–1.14)
Denmark [ 18 ] 62,000 Unrehydrated: 1.0% 56 48 Biennial 0.82 (0.68–0.99) 1.00 (0.87–1.13)
Sweden [ 24 ] 68,308 Unrehydrated: 1.9% 52 50 Varied 0.84 (0.71–0.99) 0.96 (0.86–1.06)
  Rehydrated: 5.8%          

Immunochemical FOBTs (iFOBT or FIT): Nonrandomized Controlled Trial Evidence to Assess Lesion Detection

The immunochemical FOBT (iFOBT or FIT) was developed to detect intact human hemoglobin. The advantage of FIT over gFOBT is that it does not detect hemoglobin from nonhuman dietary sources. Also, FIT does not detect partly digested human hemoglobin that comes from the upper respiratory or GI tract. Preliminary studies of several commercially developed FIT tests define their sensitivity and specificity compared with concurrently performed colonoscopy. The studies also examine these outcomes for different cutpoints, and the benefit of multiple versus single stool samples.[ 25 ][ 26 ]

Overall, FIT testing is much more sensitive than gFOBT, and it is more sensitive for cancers than for benign neoplasias. As expected, higher cutpoints decrease sensitivity and increase specificity. Fecal immunochemical tests may vary with regard to numbers of stools tested and cutoff values for a positive result.[ 26 ]

A systematic review of FIT studies in 2019 found 31 studies, with 120,255 participants and 18 types of FIT tests, that used screening colonoscopy as the reference standard, thus allowing calculation of test sensitivity and specificity.[ 27 ] Performance depended on the threshold for a positive result, so that a threshold of 10 µg/g (micrograms of hemoglobin per gram of feces) resulted in a CRC sensitivity of 0.91 (95% CI, 0.84–0.95) and a specificity of 0.90 (95% CI, 0.86–0.93), while a threshold greater than 20 µg/g resulted in a sensitivity of 0.71 (95% CI, 0.56–0.83) with specificity of 0.95 (95% CI, 0.94–0.96). For advanced adenomas, at a threshold of 10 µg/g, sensitivity was 0.40 (95% CI, 0.33–0.47) with a specificity of 0.90 (95% CI, 0.87–0.93). Comparison of three FITS at three thresholds was inconclusive because CI's overlapped and the comparisons were across rather than within studies. Overall, FIT appears to provide a substantially improved sensitivity compared with gFOBT, although with some compromise in specificity.

The diagnostic sensitivity of FIT testing may vary depending on lesion location in the colon. Proximal lesions may be harder to detect for several reasons, including that they may arise from serrated lesions that are flat and, because they are less vascular than traditional adenomas, tend to bleed less frequently. In a population-based screening program of every-other-year FIT (set to detect 100 ng of hemoglobin per mL of buffer) testing, individuals who had six FITs over time were assessed to learn the frequency with which proximal and distal lesions were discovered.[ 28 ] Over 12 years (2002–2014), 123,000 participants had 441,000 FITs. The detection rate for proximal colon cancer declined only from the first to the second screening round (0.63–0.36 per 1,000 screened participants), while the rate for both distal colon and rectal cancer decreased across all six rounds (distal cancer, 1.65 in the first round to 0.17 in the sixth round). (Similar trends occurred for advanced adenomas.) The proportional interval cancer rate—the number of cancers observed versus expected—was higher in the proximal colon than in the distal colon (25.2% vs. 6.0%), suggesting that many proximal cancers (or their immediate precursors) may have been missed by FIT. These results suggest that FIT is less sensitive for proximal CRC and certainly for advanced adenomas, although it is possible that the miss rate may have been inflated if colonoscopy done in response to a positive FIT had missed a precursor lesion. Overall, these results raise questions about the degree of efficacy of FIT in preventing proximal CRC mortality.

The performance and acceptability of FIT over time was assessed by Kaiser-Permanente of Northern and Southern California in a screening program. A retrospective cohort of 323,349 persons aged 50 to 70 years was followed for up to four screening rounds over 4 years. Of patients invited, participation in round one was 48.2%, and of those remaining eligible, 75.3% to 86.1% participated in subsequent rounds. The authors reported that “programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round one and 73.4% to 78.0% in subsequent rounds.” An important observation was the degree of participation found. One limitation of the study is that it was not clear how work-up bias was addressed; e.g., when individuals with a positive test result are preferentially worked up to ascertain the presence or absence of CRC, while individuals with a negative test, but who might have CRC, are not. Although a look-back method was used to ascertain whether an individual had cancer, it is not clear that the duration of follow-up was long enough to discover everyone who should have been included in the denominator of the sensitivity calculation. Nevertheless, the results suggested that subsequent FIT results were at least partially independent of previous results. Longer follow-up may help clarify this issue. Mortality reduction could not be assessed in this study.[ 29 ]

Potential false-positive test results because of an increased risk of upper GI bleeding are of concern with FOBT testing and pretest protocols, therefore; low-dose aspirin regimens are discontinued for a week or more before FOBT. The performance of FIT was tested in an ongoing diagnostic study (2005–2009) at 20 internal medicine GI practices in southern Germany. Nineteen hundred seventy-nine patients (233 regular low-dose aspirin users and 1,746 never users) were identified in the records for inclusion in the analysis. All patients provided one stool sample taken within a week before colonoscopy preparation, which was collected according to instructions in a container that was kept refrigerated or frozen until rendered to the clinic on the day of colonoscopy, and the patients agreed to complete a standard questionnaire regarding the use of analgesics and low-dose aspirin (for prevention of cardiovascular disease). Stool samples were thawed within a median of 4 days after arrival at the central laboratory (shipped frozen from the recipient clinics). Fecal occult blood levels were measured by two automated FIT tests according to the manufacturer’s instructions (RIDASCREEN Haemoglobin and RIDASCREEN Haemo-/Haptoglobin Complex, r-biopharm, Bensheim, Germany) following clinical procedures and blinded to colonoscopy results. Advanced neoplasms were found in 24 aspirin users (10.3%) and in 181 nonusers (10.4%). At the cut point recommended by the manufacturer, sensitivities for the two tests were 70.8% (95% CI, 48.9%–87.4%) for users compared with 35.9% (95% CI, 28.9%–43.4%) for nonusers and 58.3% (95% CI, 36.6%–77.9%) for users compared with 32% (95% CI, 25.3%–39.4%) for nonusers (P = .001 and P = .01, respectively). Specificities were 85.7% (95% CI, 80.2–90.1%) for users compared with 89.2% (95% CI, 87.6%–90.7%) for nonusers and 85.7% (95% CI, 80.2%–90.1%) for users compared with 91.1% (95% CI, 89.5%–92.4%) for nonusers (P = .13 and P = .01, respectively). For these FITs, sensitivity for advanced neoplasms was notably higher with the use of low-dose aspirin while specificity was only slightly reduced, suggesting that there might be an advantage of aspirin use to increase sensitivity without much decrease in specificity.[ 30 ]

Sigmoidoscopy

The flexible fiberoptic sigmoidoscope was introduced in 1969. The 60 cm flexible sigmoidoscope became available in 1976.[ 31 ] The flexible sigmoidoscope permits a more complete examination of the distal colon with more acceptable patient tolerance than the older rigid sigmoidoscope. The rigid instrument can discover 25% of polyps, and the 60 cm scope can find as many as 65% of them. The finding of an adenoma by FS may warrant a colonoscopy to evaluate the more proximal portion of the colon.[ 32 ][ 33 ] The prevalence of advanced proximal neoplasia is increased in patients with a villous or tubulovillous adenoma distally and is also increased in those aged 65 years or older with a positive family history of CRC and with multiple distal adenomas.[ 34 ] Most of these adenomas are polypoid, flat, and depressed lesions, which may be somewhat more prevalent than previously recognized.[ 35 ]

Four major sigmoidoscopy screening RCTs have reported incidence and mortality results (a fifth, the Telemark trial in Norway, was very small, with 800 total participants). These are the Norwegian Colorectal Cancer Prevention (NORCCAP) trial; the United Kingdom Flexible Sigmoidoscopy Screening Trial (UKFSST); the Screening for COlon REctum (SCORE) trial in Italy; and the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (refer to Table 3). Participants were aged 55 to 74 years in PLCO, and aged 55 to 64 years in the other three trials. Together, the trials enrolled 166,000 participants in the screened groups and 250,000 participants in the control groups. Median follow-up was approximately 11 years for each group. Results were summarized in three systematic reviews. There was an 18% relative reduction in CRC incidence (RR, 0.82; 95% CI, 0.75–0.89), an overall 28% relative reduction in CRC mortality (RR, 0.72; 95% CI, 0.65–0.80), a 31% relative reduction in the incidence of distal CRC (RR, 0.69; 95% CI, 0.63–0.74), and a 46% relative reduction in the mortality of distal CRC (RR, 0.54; 95% CI, 0.43–0.67).[ 36 ] A meta-analysis showed a statistically significant, although clinically small, effect on all-cause mortality (RR, 0.97; 95% CI, 0.96–0.99).[ 37 ]

Three of the four trials above published long-term follow-up analyses of trial results. For UKFSST, median follow-up was 17.1 years. The RRs for CRC incidence and mortality were similar to those originally reported: an RR of 0.70 (95% CI, 0.62–0.79) for CRC mortality and an RR of 0.74 (95% CI, 0.70–0.80) for CRC incidence. For the PLCO trial, median follow-up was 15.8 years for incidence and 16.8 years for mortality; RRs were 0.75 (95% CI, 0.66–0.85) for CRC mortality and 0.82 (95% CI, 0.76–0.88) for CRC incidence. Median follow-up in the NORCCAP trial was approximately 15 years; HRs were 0.79 (95% CI, 0.65–0.96) for CRC mortality and 0.78 (95% CI, 0.70–0.87) for CRC incidence.[ 38 ][ 39 ]

There are no strong direct data from studies of sigmoidoscopy to determine the optimal frequency of screening tests in programs of screening.

Table 3. Randomized Controlled Screening Trials to Assess Outcome: Sigmoidoscopya
Site Population Size (Intervention) FS Rate (%) Colonoscopy Rate (%) Cumulative CRC Incidence (%) CRC Deaths per 100,000 Person-Years CRC Mortality Relative Risk (95% CI) Distal CRC Mortality Relative Risk (95% CI) CRC Incidence Relative Risk (95% CI)
CI = confidence interval; CRC = colorectal cancer; FS = flexible sigmoidoscopy.
aAdapted from Lin et al.[ 26 ]
bThe FS rate refers to the % of individuals who received FSG in the screened group.
cThe colonoscopy rate refers to the % of individuals who received a colonoscopy as a follow-up to a positive sigmoidoscopy among those who received a sigmoidoscopy. In the U.S. study, individuals with a polyp found at the time of a sigmoidoscopy were referred for diagnostic follow-up, which was generally done with a colonoscopy. In the other studies, the referral criteria for a colonoscopy depended on the histology of lesion(s) found at the time of the sigmoidoscopy.
d Half of the intervention group was also offered FOBT.
eThese data are from Lin et al.[ 26 ], eFigure 1. Forest plot of randomized controlled trials of FS screening on distal CRC mortality.
United Kingdom 2010 Intervention: 57,099 71.1 5.0 1.5 Intervention: 30 0.69 (0.59–0.80) 0.58 (0.46–0.74) 0.77 (0.70–0.84)
Control: 112,939 Control: 44
Italy 2011 Intervention: 17,136 57.8 7.8 1.6 Intervention: 35 0.78 (0.56–1.08) 0.73 (0.47–1.12) 0.82 (0.69–0.96)
Control: 17,136 Control: 44
United States 2012 Intervention: 77,445 86.6 25.3 1.5 Intervention: 29 0.74 (0.63–0.87) 0.50 (0.38–0.64) 0.79 (0.72–0.85)
Control: 77,455 Control: 39
Norway 2014 Intervention: 20,572d 63.0 19.5 1.4 Intervention: 31 0.73 (0.56–0.94) 0.87 (0.61–0.043) 0.80 (0.70–0.92)
Control: 78,220 Control: 43

Combination of FOBT and Flexible Sigmoidoscopy: Impact on Neoplasm Detection

A combination of FOBT and sigmoidoscopy might increase the detection of lesions in the left colon (compared with sigmoidoscopy alone) while also increasing the detection of lesions in the right colon. Sigmoidoscopy detects lesions in the left colon directly but detects lesions in the right colon only indirectly when a positive sigmoidoscopy (that may variously be defined as a finding of advanced adenoma, any adenoma, or any polyp) is used to trigger a colonoscopic examination of the whole colon.

In 2,885 veterans (97% male; mean age, 63 years), the prevalence of advanced adenoma at colonoscopy was 10.6%. It was estimated that combined screening with one-time FOBT and sigmoidoscopy would detect 75.8% (95% CI, 71.0%–80.6%) of advanced neoplasms. Examination of the rectum and sigmoid colon during colonoscopy was defined as a surrogate for sigmoidoscopy. This represented a small but statistically insignificant increase in the rate of detection of advanced neoplasia when compared with FS alone (70.3%; 95% CI, 65.2%–75.4%). The latter result could be achieved assuming that all patients with an adenoma in the distal colon undergo complete colonoscopy. Advanced neoplasia was defined as a lesion measuring at least 10 mm in diameter, containing 25% or more villous histology, high-grade dysplasia, or invasive cancer.[ 40 ] One-time use of FOBT differs from the annual or biennial application reported in those studies summarized in Table 2.

A study of 21,794 asymptomatic persons (72% were men), who had both colonoscopy and FIT for occult blood, compared the detection of proximal cancers as triggered by different test results. FIT alone resulted in a sensitivity of 58.3% and a specificity of 94.5% for proximal cancer diagnosis. FIT plus the finding of advanced neoplasia in the rectosigmoid colon yielded a sensitivity of 62.5% and a specificity of 93%. In this study, the addition of sigmoidoscopy to FIT did not substantially improve the detection of proximal colon cancers, compared with FIT alone.[ 41 ]

Colonoscopy

Because there are no completed RCTs of the impact of colonoscopy on CRC mortality or incidence, evidence of benefit is indirect. Most indirect evidence is about detection rate of lesions that may be clinically important (like early CRC or advanced adenomas). Some case-control results are available. Five RCTs of colonoscopy (NCT01239082, NCT00883792, NCT00906997, NCT02078804, and ChiCTR1900025257) have been initiated.

Although the evidence is indirect, the sensitivity of a CRC screening test for adenomas (and for CRC) may be useful in considering its possible clinical usefulness, given that there are no completed RCTs of the impact of colonoscopy on CRC mortality or incidence. Colonoscopy is commonly considered the gold standard because it directly assesses the physical presence of lesions in the colon. However, colonoscopy can miss roughly 10% of cancers and advanced adenomas, because of suboptimal bowel cleansing, or because lesions may be hidden behind folds (or haustra) in the colon, or because of suboptimal examination by the endoscopist. Recent data suggest that the magnitude of a colonoscopist's adenoma-detection rate (commonly measured as the proportion of colonoscopies in which an adenoma is found) is related to reduced incidence of CRC.

Adenoma detection rate (ADR)

Detection rates in colonoscopy screening vary with the rate at which the endoscopist examines the colon while withdrawing the scope. In one study, there were differences among gastroenterologists in the rates of detection of adenomas (range of the mean number of lesions per patient screened, 0.10–1.05; range of the percentage of patients with adenomas, 9.4%–23.7%) and the times of withdrawal of the scope (3.1–16.8 minutes for procedures not including polyp removal). Examiners whose mean withdrawal time was 6 minutes or more had higher detection rates than those with mean withdrawal times of less than 6 minutes (28.3% vs. 11.8%; P < .001 for any neoplasia and 6.4% vs. 2.6%; P < .005 for advanced neoplasia).[ 42 ]

In the first 10 years of the German CRC screening program, detection of nonadvanced adenomas increased in men from 13.3% to 22.3% and in women from 8.4% to 14.9%. The great majority of the nonadvanced adenomas, however, were small (<0.5 cm) and had uncertain clinical significance. The detection of advanced adenomas and CRC increased by a much smaller amount.[ 43 ]

Overall detection rate of adenomas and cancer may be affected by how thoroughly endoscopists search for flat adenomas and flat cancer. While the phenomenon of flat neoplasms has been appreciated for years in Japan, it has more recently been described in the United States. In a study in which endoscopists used high-resolution white-light endoscopes, flat or nonpolypoid lesions were found to account for only 11% of all superficial colon lesions, but these flat or nonpolypoid lesions were about 9.8 times as likely as polypoid lesions to contain cancer (in situ neoplasia or invasive cancer).[ 35 ] However, because the definition of flat or nonpolypoid was height less than one-half of the diameter, it is likely that many lesions classified as nonpolypoid in this study would be routinely found and described by U.S. endoscopists as sessile. The existence of very flat or depressed lesions—depressed lesions are very uncommon but are highly likely to contain cancer—requires that endoscopists pay increasing attention to this problem.[ 44 ] Flat lesions may play a role in the phenomenon of missed cancers.[ 45 ]

The impact of ADRs was assessed by a health maintenance organization in follow-up after 314,872 colonoscopies done from 1998 to 2010 by 136 gastroenterologists, each of whom had done at least 300 colonoscopies during that period. The goal was to determine rates of interval CRC, interval advanced CRC, and CRC death, and to relate those rates to a gastroenterologist’s ADR. There were 712 interval cancers (155 advanced) and 147 CRC deaths. The risk of interval cancer from lowest-to-highest quintile of ADR was 9.8, 8.6, 8.0, 7.0, and 4.8 per 10,000 person-years of follow-up. The adjusted hazard ratio, for physicians in the highest quintile compared with the lowest, was 0.52 for any interval CRC, 0.43 for advanced CRC, and 0.38 for fatal CRC. Each 1.0% increase in ADR was associated with a 3% decrease in risk of cancer, although the CI for each quintile was broad. Limitations of the study include the inability to determine which specific feature of ADR led to reduced interval cancer; for example, it is unclear whether it was due to the following:

Another limitation is that the harms of a colonoscopy associated with ADR could not be measured.[ 46 ]

Nonrandomized controlled trial evidence about colorectal cancer incidence or mortality reduction

Although there is no RCT to assess reduction of CRC incidence or mortality by colonoscopy, some case-control evidence is available.[ 47 ] Based on case-control data about sigmoidoscopy, noted above, there was speculation that protection for the right colon might be similar to that for the left colon. A 2009 case-control study of colonoscopy raised questions about whether the impact of colonoscopy on proximal lesions might be different than the impact on distal lesions.[ 48 ] Using a province-wide administrative database in Ontario, Canada, investigators compared cases of persons who had received a diagnosis of CRC from 1996 to 2001 and had died by 2003. Controls were selected from persons who did not die of CRC. Billing claims were used to assess exposure to previous colonoscopy. The OR for the association between complete colonoscopy and distal lesions was 0.33, suggesting a substantial mortality reduction. For proximal lesions, however, the OR of 0.99 indicated virtually no mortality reduction. However, this study had limited data about whether examinations were complete to the cecum and about bowel prep. Further, many endoscopists were nongastroenterologists.

A case-control study assessed CRC reduction (not CRC mortality reduction) in the right side versus the left side. In a population-based study from Germany, data were obtained from administrative records and medical records; 1,688 case patients (with CRC) were compared with 1,932 participants (without CRC), aged 50 years or older.[ 49 ] Data were collected about demographics, risk factors, and previous screening examinations. According to colonoscopy records, the cecum was reached 91% of the time. Colonoscopy in the previous 10 years was associated with an OR for any CRC of 0.23, for proximal CRC of 0.44, and for distal CRC of 0.16. While this study did not assess CRC mortality, the results suggested that the magnitude of the right-side versus the left-side difference may be smaller than previously found.[ 48 ] It would be extremely useful to assess right side-versus left side differences in a RCT.

Other case-control data suggest a reduction of CRC incidence on the right-side of about 64% compared with about 74% on the left-side.[ 50 ]

Because there is no RCT evidence and case-control evidence is limited, it is important to consider the degree of mortality reduction from colonoscopy. While a figure of 90% is sometimes cited as the degree of mortality reduction,[ 51 ] the question will not be properly answered until the European RCT that has a control group of routine care that involves minimal screening of any kind is completed.[ 52 ] Reliable results from colonoscopy RCTs are needed to confirm the studies of FS that suggest a mortality reduction of approximately 50% might occur in the right colon, similar to the demonstrated impact of FS in the left colon. This generalization is limited by a number of factors, including that proximal lesions may have a different pathology (e.g., a serrated appearance and different molecular pathway).

Virtual Colonoscopy (Computed Tomographic Colonography [CTC])

Virtual colonoscopy (also known as CTC or CT pneumocolon) refers to the examination of computer-generated images of the colon constructed from data obtained from an abdominal CT scan. These images simulate the effect of a conventional colonoscopy. Patients must take laxatives to clean the colon before the procedure, and the colon is insufflated with air (sometimes carbon dioxide) by insertion of a rectal tube just before radiographic examination.[ 53 ]

A large, paired-design study was conducted by the American College of Radiology Imaging Network group, with 2,531 average-risk people (prevalence of polyps or cancer ≥10 mm, 4%; mean age about 58 years) screened with both CTC and optical colonoscopy (OC). The gold standard was the OC, including repeat OC exams for people with lesions found by CTC but not by OC. Of 109 people with at least one adenoma or cancer 10 mm or larger, 98 (90%) were detected by CTC (referring everyone with a CTC lesion of ≥5 mm). Specificity was 86%, and PPV was 23%. There are several concerns from this study, including the following:

Unknowns from the study include the following for either OC or CTC:[ 54 ]

Another study reported similar sensitivity and specificity in persons with an increased risk of CRC.[ 55 ] In this study, the sensitivity of OC could not be determined because it was done in an unblinded manner. This study suggested that virtual colonoscopy might be an acceptable screening or surveillance test for persons with a high risk of CRC, but this cross-sectional study did not address outcome or frequency of testing in high-risk persons.

Some studies have assessed how well virtual colonoscopy can detect colorectal polyps without a laxative prep. The question is of great importance for implementation because the laxative prep required by both conventional colonoscopy and virtual colonoscopy is considered a great disadvantage by patients. By tagging feces with iodinated contrast material ingested during several days before the procedure, investigators in one study were able to detect lesions larger than 8 mm with 95% sensitivity and 92% specificity.[ 56 ] The particular tagging material used in this study caused about 10% of patients to become nauseated; however, other materials are being assessed.

Another study [ 57 ] utilized low-fiber diet, orally ingested contrast, and "electronic cleansing," a process that subtracts tagged feces. CTC identified 91% of persons with adenomas 10 mm or larger, but detected fewer (70%) lesions of at least 8 mm. Patients who received both CTC and OC preferred CTC to OC (290 vs. 175). This study shows that CTC without a laxative prep detects small 1 cm lesions with high sensitivity and is acceptable to patients. Long-term utilization of CTC will depend on several issues, including the frequency of follow-up exams that would be needed to detect smaller lesions that were undetected and may grow over time.

Extracolonic abnormalities are commonly detected with CTC. Fifteen percent of patients in an Australian series of 100 patients, referred for colonography because of symptoms or family history, were found to have extracolonic findings, and 11% of the patients needed further medical workups for renal, splenic, uterine, liver, and gallbladder abnormalities.[ 58 ] In another study, 59% of 111 symptomatic patients referred for clinical colonoscopy in a Swedish hospital between June 1998 and September 1999 were found to have moderate or major extracolonic conditions on CTC. CTC was performed immediately before a colonoscopy and these findings required further evaluation. The extent to which follow-up of these incidental findings benefited patients is unknown.[ 59 ]

Sixty-nine percent of 681 asymptomatic patients in Minnesota had extracolonic findings, of which 10% were considered to be highly important by the investigators, and required further medical workup. Suspected abnormalities involved kidney (34), chest (22), liver (8), ovary (6), renal or splenic arteries (4), retroperitoneum (3), and pancreas (1);[ 60 ] however, the extent to which these findings will contribute to benefits or harms is uncertain. Two other studies, one large (N = 2,195) and one small (n = 136) examined the moderate or high importance of extracolonic findings from CTC. The larger study [ 61 ] found that 8.6% of patients had an extracolonic finding of at least moderate importance, while 24% of patients in the smaller study [ 62 ] required some evaluation for an extracolonic finding. The larger study found nine cancers from these evaluations, at a partial cost (they did not include all costs) of $98.56 per patient initially screened. The smaller study found no important lesions from evaluation, at a cost of $248 per person screened. Both of these estimates of cost are higher than previous studies have found. The extent to which any patients benefited from the detection of extracolonic findings is not clear. Because both of these studies were conducted in academic medical centers, the generalizability to other settings is also not clear. Neither of these studies examined the effect of extracolonic findings on patient anxiety and psychological function.

Technical improvements involving both the interpretation methodology, such as three dimensional (3-D) imaging, and bowel preparation are under study in many centers. While specificity for detection of polyps is homogeneously high in many studies, sensitivity can vary widely. These variations are attributable to a number of factors including characteristics of the CT scanner and detector, width of collimation, mode of imaging (two dimensional [2-D] vs. 3-D and/or fly-through), and variability in the expertise of radiologists.[ 63 ]

Digital Rectal Examination

A case-control study reported that routine digital rectal examination was not associated with any statistically significant reduction in mortality from distal rectal cancer.[ 64 ]

Detection of DNA Mutations in the Stool

The molecular genetic changes that are associated with the development of colorectal adenomas and carcinoma have been well characterized.[ 65 ] Advanced techniques have been developed to detect several of these gene mutations that have been shed into the stool.[ 66 ][ 67 ][ 68 ][ 69 ] Stool DNA testing was recently assessed in a prospective study of asymptomatic persons who received colonoscopy, three-card FOBT (Hemoccult II), and stool DNA testing based on a panel of markers assessing 21 mutations. Conducted in a blinded way with prestated hypotheses and analyses, the study found that among 4,404 patients, the DNA panel had a sensitivity for CRC of 51.6% (for all stages of CRC) versus 12.9% for Hemoccult II, while the false-positive rates were 5.6% and 4.8%, respectively.[ 70 ][ 71 ]

A next-generation multitargeted stool test combined methylation markers for NDRG4 and BMP3, several KRAS mutations, and a human hemoglobin immunoassay. The markers, each quantitated separately, were combined using an algorithm in a prespecified multivariable analysis. The assay’s sensitivity and specificity were compared with a commercial FIT test (OC FIT-CHEK Polymedco), using colonoscopy as the gold standard. Among 12,776 participants who had colonoscopy screening, were enrolled from 2011 through 2012 at 90 sites in the United States and Canada, and were aged 50 to 84 years (and weighted toward >65 years), 9,989 had fully evaluable results. There were 65 CRC and 757 advanced adenomas or sessile serrated polyps 1 cm or greater. The sensitivity for CRC was 92.3% (60 of 65 CRC) for the multitargeted test and 73.8% for FIT. Sensitivity for advanced lesions was 42.4% for the multitargeted test and 23.8% for FIT. Sensitivity for high-grade dysplasia was 69.2% for the multitarget test and 46.2% for FIT. Sensitivity for serrated sessile polyps 1 cm or greater was 42.4% for the multitargeted test and 5.1% for FIT. Specificities were 86.6% for the multitargeted test and 94.9% for FIT, using nonadvanced or negative colonoscopy results, and were 89.8% and 96.4% for totally negative colonoscopy results. A receiver operating characteristic (ROC) analysis showed that the multitargeted test has higher sensitivity than FIT alone, even when the FIT cutoff is reduced to try to increase sensitivity. A limitation is that there were no data about performance of repeated testing over time and what may be an appropriate testing interval.[ 72 ]

Overall, the multitargeted test was more sensitive than FIT for both CRC and advanced precancerous lesions, but the test was less specific.[ 72 ] The U.S. Food and Drug Administration approved this multitargeted test for colorectal screening in 2014.

Adherence to Screening

Benefit from CRC screening can only occur if eligible people are actually screened. There have been problems with screening adherence, particularly for low income and uninsured people. There has also been concern that some people may adhere less to screening with a colonoscopy than with fecal tests. One well-conducted RCT found that, among an uninsured population, mailed FIT-kit outreach and follow-up reminder phone calls resulted in an adherence rate of 40.7%. Mailed colonoscopy invitations and follow-up phone reminders resulted in a 24.6% adherence rate. The usual-care adherence rate in this trial was 12.1%.[ 73 ]

Tailoring Screening to Risk

Benefit of screening might be improved by tailoring the recommended screening test to a person’s degree of CRC risk. For example, if a subgroup of young women were to have a substantially lower risk of proximal neoplasms, then recommending sigmoidoscopy instead of colonoscopy (both are recommended by the U.S. Preventive Services Task Force without preference, as part of a program of screening persons with average risk) might lead to higher compliance.

In a study to identify persons in an average-risk group who had a higher versus lower risk of advanced neoplasia (CRC and advanced adenomas) anywhere in the colon, 2,993 persons having a screening colonoscopy were stratified by age, gender, waist circumference, smoking, and family history (persons in high-risk family categories, e.g., Lynch syndrome or adenomatous polyposis coli, were excluded). In a classification system derived in a training set, the risks of advanced neoplasm in four groups were: 1.92%, 4.88%, 9.93%, and 24%. In the two lowest-risk groups, sigmoidoscopy would have detected 51 (73%) of 70 advanced neoplasms. In the independent validation set, results were similar. Whether this system increases overall compliance has yet to be determined.[ 74 ]

A similar stratification system based on age, gender, smoking, and family history—and combined with FIT—was tested in Asia to determine whether use of the stratification system plus FIT could detect which persons need colonoscopy. If either the stratification system or FIT was positive, a person was recommended for colonoscopy. Using this strategy, 95% of persons with CRC were correctly told to have colonoscopy.[ 75 ]

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  29. Jensen CD, Corley DA, Quinn VP, et al.: Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study. Ann Intern Med 164 (7): 456-63, 2016.[PUBMED Abstract]
  30. Brenner H, Tao S, Haug U: Low-dose aspirin use and performance of immunochemical fecal occult blood tests. JAMA 304 (22): 2513-20, 2010.[PUBMED Abstract]
  31. Fath RB, Winawer SJ: Endoscopic screening by flexible fiberoptic sigmoidoscopy. Front Gastrointest Res 10: 102-111, 1986.[PUBMED Abstract]
  32. Read TE, Read JD, Butterly LF: Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy. N Engl J Med 336 (1): 8-12, 1997.[PUBMED Abstract]
  33. Wallace MB, Kemp JA, Trnka YM, et al.: Is colonoscopy indicated for small adenomas found by screening flexible sigmoidoscopy? Ann Intern Med 129 (4): 273-8, 1998.[PUBMED Abstract]
  34. Levin TR, Palitz A, Grossman S, et al.: Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy. JAMA 281 (17): 1611-7, 1999.[PUBMED Abstract]
  35. Soetikno RM, Kaltenbach T, Rouse RV, et al.: Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA 299 (9): 1027-35, 2008.[PUBMED Abstract]
  36. Tinmouth J, Vella ET, Baxter NN, et al.: Colorectal Cancer Screening in Average Risk Populations: Evidence Summary. Can J Gastroenterol Hepatol 2016: 2878149, 2016.[PUBMED Abstract]
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  38. Miller EA, Pinsky PF, Schoen RE, et al.: 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 4 (2): 101-110, 2019.[PUBMED Abstract]
  39. Holme Ø, Løberg M, Kalager M, et al.: Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men: A Randomized Trial. Ann Intern Med 168 (11): 775-782, 2018.[PUBMED Abstract]
  40. Lieberman DA, Weiss DG; Veterans Affairs Cooperative Study Group 380: One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon. N Engl J Med 345 (8): 555-60, 2001.[PUBMED Abstract]
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  42. Barclay RL, Vicari JJ, Doughty AS, et al.: Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. N Engl J Med 355 (24): 2533-41, 2006.[PUBMED Abstract]
  43. Brenner H, Altenhofen L, Kretschmann J, et al.: Trends in Adenoma Detection Rates During the First 10 Years of the German Screening Colonoscopy Program. Gastroenterology 149 (2): 356-66.e1, 2015.[PUBMED Abstract]
  44. Lieberman D: Nonpolypoid colorectal neoplasia in the United States: the parachute is open. JAMA 299 (9): 1068-9, 2008.[PUBMED Abstract]
  45. Robertson DJ, Lieberman DA, Winawer SJ, et al.: Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut 63 (6): 949-56, 2014.[PUBMED Abstract]
  46. Corley DA, Jensen CD, Marks AR, et al.: Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 370 (14): 1298-306, 2014.[PUBMED Abstract]
  47. Nishihara R, Wu K, Lochhead P, et al.: Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 369 (12): 1095-105, 2013.[PUBMED Abstract]
  48. Baxter NN, Goldwasser MA, Paszat LF, et al.: Association of colonoscopy and death from colorectal cancer. Ann Intern Med 150 (1): 1-8, 2009.[PUBMED Abstract]
  49. Brenner H, Chang-Claude J, Seiler CM, et al.: Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med 154 (1): 22-30, 2011.[PUBMED Abstract]
  50. Doubeni CA, Weinmann S, Adams K, et al.: Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study. Ann Intern Med 158 (5 Pt 1): 312-20, 2013.[PUBMED Abstract]
  51. Smith MJ: Colon cancer screening hitting its stride but obstacles impair reaching final goal. Gastroenterology and Endoscopy News 59 (3): 9, 2008. [Refer to "Screening: it’s not just a good idea, it’s the law … almost" within the article].[PUBMED Abstract]
  52. Bretthauer M, Ekbom A, Malila N, et al.: [Politics and science in colorectal cancer screening] Tidsskr Nor Laegeforen 126 (13): 1766-7, 2006.[PUBMED Abstract]
  53. Ferrucci JT: Colon cancer screening with virtual colonoscopy: promise, polyps, politics. AJR Am J Roentgenol 177 (5): 975-88, 2001.[PUBMED Abstract]
  54. Johnson CD, Chen MH, Toledano AY, et al.: Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med 359 (12): 1207-17, 2008.[PUBMED Abstract]
  55. Regge D, Laudi C, Galatola G, et al.: Diagnostic accuracy of computed tomographic colonography for the detection of advanced neoplasia in individuals at increased risk of colorectal cancer. JAMA 301 (23): 2453-61, 2009.[PUBMED Abstract]
  56. Iannaccone R, Laghi A, Catalano C, et al.: Computed tomographic colonography without cathartic preparation for the detection of colorectal polyps. Gastroenterology 127 (5): 1300-11, 2004.[PUBMED Abstract]
  57. Zalis ME, Blake MA, Cai W, et al.: Diagnostic accuracy of laxative-free computed tomographic colonography for detection of adenomatous polyps in asymptomatic adults: a prospective evaluation. Ann Intern Med 156 (10): 692-702, 2012.[PUBMED Abstract]
  58. Edwards JT, Wood CJ, Mendelson RM, et al.: Extracolonic findings at virtual colonoscopy: implications for screening programs. Am J Gastroenterol 96 (10): 3009-12, 2001.[PUBMED Abstract]
  59. Hellström M, Svensson MH, Lasson A: Extracolonic and incidental findings on CT colonography (virtual colonoscopy). AJR Am J Roentgenol 182 (3): 631-8, 2004.[PUBMED Abstract]
  60. Gluecker TM, Johnson CD, Wilson LA, et al.: Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology 124 (4): 911-6, 2003.[PUBMED Abstract]
  61. Pickhardt PJ, Hanson ME, Vanness DJ, et al.: Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology 249 (1): 151-9, 2008.[PUBMED Abstract]
  62. Kimberly JR, Phillips KC, Santago P, et al.: Extracolonic findings at virtual colonoscopy: an important consideration in asymptomatic colorectal cancer screening. J Gen Intern Med 24 (1): 69-73, 2009.[PUBMED Abstract]
  63. Mulhall BP, Veerappan GR, Jackson JL: Meta-analysis: computed tomographic colonography. Ann Intern Med 142 (8): 635-50, 2005.[PUBMED Abstract]
  64. Herrinton LJ, Selby JV, Friedman GD, et al.: Case-control study of digital-rectal screening in relation to mortality from cancer of the distal rectum. Am J Epidemiol 142 (9): 961-4, 1995.[PUBMED Abstract]
  65. Kinzler KW, Vogelstein B: Lessons from hereditary colorectal cancer. Cell 87 (2): 159-70, 1996.[PUBMED Abstract]
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  73. Gupta S, Halm EA, Rockey DC, et al.: Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med 173 (18): 1725-32, 2013.[PUBMED Abstract]
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Evidence of Harms

Potential harms are associated with the modalities used to screen for colorectal cancer (CRC), some of which have sufficient evidence and some that do not.

Overview

The tables for each screening test below show the magnitude of burden for several categories of harms encountered along the screening cascade. The magnitude of harms is a combination of the frequency and severity of harm, as perceived by the patient.

Harms are defined broadly as any negative effect on individuals or populations resulting from being involved in the screening process (cascade) compared with not screening. Potential harms are organized according to the type of harm (e.g., physical, psychological, and hassle/opportunity costs) and when they occur in the screening cascade (e.g., screening test/workup; screening test/workup results; surveillance and surveillance results; and early treatment and overtreatment). For example, potential harms of screening colonoscopy include harms of the screening test itself (e.g., perforation and bleeding), results of the screening test (e.g., anxiety from an abnormal result), surveillance (e.g., harms of more frequent colonoscopies), and treatment (e.g., earlier treatment or overtreatment). For other colorectal cancer screening tests, there are also harms associated with the workup (e.g., colonoscopy for positive fecal occult blood test [FOBT]). A recent study of three major hospitals found evidence that 71% of endoscopes tested positive for bacteria after cleaning and high-level disinfection of the scopes. This raises concern for endoscopy-associated pathogen transmission and patient safety, although no patients were involved in the study and the implications for patients are unknown.[ 1 ] For all aspects of participating in the screening cascade, there are time/effort and opportunity costs (nonfinancial harms) for the patient. We do not include here any financial harms to the patient/family, nor any psychological harm from anticipation of future financial costs related to screening.

Table 4. Colonoscopy
Stage of Screening Cascade
Physical Psychological Time/Effort, Opportunity
CRC = colorectal cancer.
Screening Test/Workup Average 0.3% complications requiring hospitalization or resulting in death, higher with polypectomy and in older patients (fair evidence) Percentage of people who suffer psychological distress on consideration of having colonoscopy; severity and duration (insufficient evidence) About 38 hours (median) required for preparation, procedure, sedation (one study, fair evidence) [ 2 ]
Discomfort of preparation and procedure; adverse effects of preparation (insufficient evidence to determine magnitude and frequency)
Complications from sedation during procedure (insufficient evidence to determine magnitude and frequency)
Screening Test/Workup Results Increased risk of suicide and cardiovascular mortality soon after diagnosis (insufficient evidence) Percentage of people who suffer psychological distress after receiving positive screening and/or pathological results; severity and duration (insufficient evidence) Time and effort required to receive and understand screening test or workup results, including extra physician visits for positive tests (insufficient evidence)
Surveillance/Results More frequent colonoscopy Percentage of people who suffer psychological distress after receiving positive screening and/or pathological results; severity and duration (insufficient evidence) Time and effort required to undergo colonoscopy (median, 38 hours, see above)
Time and effort required to receive and understand surveillance results (insufficient evidence)
Treatment (Early Treatment and Overtreatment) Overdiagnosis and overtreatment of precursor polyps or earlier treatment of CRC (may or may not receive benefit from earlier treatment) (insufficient evidence) Percentage of people who suffer psychological distress after undergoing overtreatment or earlier treatment without benefit; severity and duration (insufficient evidence) Time and effort required to receive overtreatment or earlier treatment without benefit (insufficient evidence)
Table 5. FOBT/FIT, Other Stool-Based Tests (Including Fecal DNA)
Stage of Screening Cascade
Physical Psychological Time/Effort, Opportunity
CRC = colorectal cancer; FIT= immunochemical fecal occult blood test; FOBT= fecal occult blood test; N/A = not applicable.
aWorkup test is colonoscopy. Descriptions of the associated harms can be found in the colonoscopy section (refer to the Colonoscopy section in the Evidence of Harms section of this summary for more information).
bTreatment harms will be the same for all screening tests.
Screening Test None (no evidence) Percentage of people who suffer psychological distress on consideration of having CRC screening; severity and duration (insufficient evidence) Time and effort required to change diet (if required), collect samples, and return to appropriate facility (insufficient evidence)
Screening Test Results N/A Percentage of people who suffer psychological distress after receiving positive screening results; severity and duration (insufficient evidence) Time and effort required to receive and understand screening test results, including extra physician visits or communication for positive tests (insufficient evidence)
Workupa See colonoscopy See colonoscopy See colonoscopy
Workup Results N/A See colonoscopy See colonoscopy
Surveillance/Results See colonoscopy See colonoscopy See colonoscopy
Treatment (Early Treatment and Overtreatment)b See colonoscopy See colonoscopy See colonoscopy
Table 6. Flexible Sigmoidoscopy
Stage of Screening Cascade
Physical Psychological Time/Effort, Opportunity
N/A = not applicable.
aWorkup test is colonoscopy. Descriptions of the associated harms can be found in the colonoscopy section (refer to the Colonoscopy section in the Evidence of Harms section of this summary for more information).
bTreatment harms will be the same for all screening test.
Screening Test Average serious complications for 0.03% of patients (fair evidence) [ 3 ] Percentage of people who suffer psychological distress on consideration of having colonoscopy; severity and duration (insufficient evidence) Time and effort required to perform preparation, travel to and attend screening, return to usual activities (insufficient evidence)
Screening Test Results N/A See colonoscopy See colonoscopy
Workupa See colonoscopy See colonoscopy See colonoscopy
Surveillance/Results N/A See colonoscopy See colonoscopy
Treatment (Early Treatment and Overtreatment)b See colonoscopy See colonoscopy See colonoscopy
Table 7. Computed Tomography Colonography
Stage of Screening Cascade
Physical Psychological Time/Effort, Opportunity
CRC = colorectal cancer.
Screening Test/Workup Discomfort of preparation and procedure; radiation exposure (insufficient evidence) Percentage of people who suffer psychological distress on consideration of screening; severity and duration (insufficient evidence) Time required for preparation, procedure (exact time and effort uncertain) (insufficient evidence)
Screening Test/Workup Results Increased risk of suicide and cardiovascular mortality soon after diagnosis (insufficient evidence) Percentage of people who suffer psychological distress after receiving positive screening and/or pathological results; severity and duration (insufficient evidence) Time and effort required to receive and understand screening test or workup results, including extra physician visits for positive tests (insufficient evidence)
Incidental extra-colonic findings [ 3 ]
Surveillance/Results More frequent colonoscopy Percentage of people who suffer psychological distress after receiving positive screening and/or pathological results; severity and duration (insufficient evidence) Time and effort required to undergo colonoscopy (mean, 38 hours, refer to Table 4)
Time and effort required to receive and understand surveillance results (insufficient evidence)
Treatment (Early Treatment and Overtreatment) Overdiagnosis and overtreatment of precursor polyps or earlier treatment of CRC (may or may not receive benefit from earlier treatment) (insufficient evidence) Percentage of people who suffer psychological distress undergoing overtreatment or earlier treatment without benefit; severity and duration (insufficient evidence) Time and effort required to receive overtreatment or earlier treatment without benefit (insufficient evidence)

Evidence Summary

Colonoscopy

The potential physical harms of colonoscopy include adverse effects from the preparation and adverse effects from the procedure (colonic perforation and bleeding; effects of sedation).[ 4 ][ 5 ][ 6 ] A systematic review of 60 studies that assessed complications of colonoscopy screening in asymptomatic patients found infrequent serious morbidity, which comprised major bleeding (0.8/1,000 procedures; 95% confidence interval [CI], 0.18–1.63) and perforation (0.07/1,000 procedures; 95% CI, 0.006–0.17), and only minor and short-lasting psychological harms.[ 7 ] These complications can be serious, requiring hospitalization. Colonic perforation and serious bleeding occur more often with biopsy or polypectomy, with an overall average of three to five serious complications per 1,000 procedures. The physical harm of discomfort during the procedure has been reduced by sedation, although sedation has its own potential for physical harm (magnitude and severity uncertain due to insufficient evidence).

Physical harms are also associated with further steps in the screening cascade, including diagnosis of CRC (some large ecologic studies have shown an increase in suicide soon after diagnosis) and overdiagnosis/overtreatment due to treating lesions that would never have caused the patient important problems (evidence insufficient to determine magnitude and severity).

The potential psychological harms of colonoscopy include anticipation of the procedure and anxiety while awaiting the results of biopsy reports. For people with polyps, there may be increased distress in considering oneself at increased risk of CRC (evidence insufficient). For people newly diagnosed with CRC, many will experience increased anxiety and depression for at least 6 months, as prognosis and treatment are discussed (evidence insufficient).

The harm of time/effort and opportunity costs involved in moving through the demands of the screening cascade are present throughout the process (evidence insufficient to determine frequency and severity).

FOBT/immunochemical FOBT (FIT)

The potential physical harms of fecal-based testing include the same harms as for colonoscopy for people with a positive test who have been referred for diagnostic colonoscopy.

The potential psychological harms, as well as time/effort and opportunity costs are also similar to the description above for colonoscopy (refer to the Colonoscopy section in the Evidence of Harms section of this summary for more information).[ 8 ] These harms are associated with moving through the screening cascade, regardless of the initial screening test. Although it is highly likely that these psychological harms, plus time/effort and opportunity costs, do occur, the exact frequency and severity of these harms are uncertain because of insufficient evidence.

Sigmoidoscopy

The potential physical harms of sigmoidoscopy are considerably less than those of colonoscopy, with a less intensive preparation. Serious procedural complications occur in perhaps three in 10,000 sigmoidoscopies compared with in three in 1,000 colonoscopies.[ 3 ] There is usually no sedation with sigmoidoscopy, thus again lowering the potential for complications.

The potential psychological harms of sigmoidoscopy screening, as well as the time/effort and opportunity costs of screening, are the same as given above for other screening strategies.

Computed tomography colonography (CTC)

The potential physical harms due directly to the procedure of CTC are less than either colonoscopy or sigmoidoscopy, with rare procedural complications.[ 3 ] However, CTC does involve repeated radiation exposure, with uncertain associated harms, and it also detects a number of extra-colonic incidental findings.[ 9 ] [ 10 ][ 11 ][ 12 ][ 13 ] Incidental findings have been detected in 40% to 98% of CTCs, with a variable number of these considered significant enough to proceed with further diagnostic testing. As there is little evidence that early detection of any of these findings could improve health outcomes for patients, these findings may be considered as harms until proven otherwise.

The potential psychological harms or time/effort and opportunity costs for CTC are similar to the descriptions above for patients moving through the screening cascade (evidence insufficient to determine frequency and severity).

参考文献
  1. Ofstead CL, Heymann OL, Quick MR, et al.: Residual moisture and waterborne pathogens inside flexible endoscopes: Evidence from a multisite study of endoscope drying effectiveness. Am J Infect Control 46 (6): 689-696, 2018.[PUBMED Abstract]
  2. Jonas DE, Russell LB, Sandler RS, et al.: Value of patient time invested in the colonoscopy screening process: time requirements for colonoscopy study. Med Decis Making 28 (1): 56-65, 2008 Jan-Feb.[PUBMED Abstract]
  3. Whitlock EP, Lin JS, Liles E, et al.: Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 149 (9): 638-58, 2008.[PUBMED Abstract]
  4. Lin JS, Piper MA, Perdue LA, et al.: Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 315 (23): 2576-94, 2016.[PUBMED Abstract]
  5. Levin TR, Zhao W, Conell C, et al.: Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med 145 (12): 880-6, 2006.[PUBMED Abstract]
  6. Warren JL, Klabunde CN, Mariotto AB, et al.: Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med 150 (12): 849-57, W152, 2009.[PUBMED Abstract]
  7. Vermeer NC, Snijders HS, Holman FA, et al.: Colorectal cancer screening: Systematic review of screen-related morbidity and mortality. Cancer Treat Rev 54: 87-98, 2017.[PUBMED Abstract]
  8. Bobridge A, Bampton P, Cole S, et al.: The psychological impact of participating in colorectal cancer screening by faecal immuno-chemical testing--the Australian experience. Br J Cancer 111 (5): 970-5, 2014.[PUBMED Abstract]
  9. Kimberly JR, Phillips KC, Santago P, et al.: Extracolonic findings at virtual colonoscopy: an important consideration in asymptomatic colorectal cancer screening. J Gen Intern Med 24 (1): 69-73, 2009.[PUBMED Abstract]
  10. Yee J, Kumar NN, Godara S, et al.: Extracolonic abnormalities discovered incidentally at CT colonography in a male population. Radiology 236 (2): 519-26, 2005.[PUBMED Abstract]
  11. Hara AK, Johnson CD, MacCarty RL, et al.: Incidental extracolonic findings at CT colonography. Radiology 215 (2): 353-7, 2000.[PUBMED Abstract]
  12. Gluecker TM, Johnson CD, Wilson LA, et al.: Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology 124 (4): 911-6, 2003.[PUBMED Abstract]
  13. Xiong T, McEvoy K, Morton DG, et al.: Resources and costs associated with incidental extracolonic findings from CT colonogaphy: a study in a symptomatic population. Br J Radiol 79 (948): 948-61, 2006.[PUBMED Abstract]
Changes to This Summary (06/30/2021)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Description of the Evidence

Added Howlader et al. as reference 3.

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about colorectal cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Screening and Prevention Editorial Board. PDQ Colorectal Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/colorectal/hp/colorectal-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389266]

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