Skip to navigation bar Skip to breadcrumbs Skip to page content
clear place holder
Envelope icon E-mail Updates Teal square Text size:  a A A
Choose another version >>

Archived Final Evidence Summary

Other Supporting Document for Colorectal Cancer: Screening

Originally published on: December 12, 2014

This recommendation statement is currently archived and inactive. It should be used for historical purposes only. Click here for copyright and source information .

Disclaimer:Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Archived: Preface

A Targeted, Updated Systematic Review for the U.S. Preventive Services Task Force (USPSTF)

October 2008


Prepared by E.P. Whitlock, J.S. Lin, E. Liles, T.L. Beil, and R. Fu.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This report was first published in Annals of Internal Medicine 2008;149:638-58.

Archived: Abstract

Background: In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended colorectal cancer screening for adults 50 years of age or older but concluded that evidence was insufficient to prioritize among screening tests or evaluate newer tests, such as computed tomographic (CT) colonography.

Purpose: To review evidence related to knowledge gaps identified by the 2002 recommendation and to consider community performance of screening endoscopy, including harms.

Data Sources: MEDLINE, Cochrane Library, expert suggestions, and bibliographic reviews.

Study Selection: Eligible studies reported performance of colorectal cancer screening tests or health outcomes in average-risk populations and were at least of fair quality according to design-specific USPSTF criteria, as determined by 2 reviewers.

Data Extraction: Two reviewers verified extracted data.

Data Synthesis: Four fecal immunochemical tests have superior sensitivity (range, 61% to 91%), and some have similar specificity (97% to 98%), to the Hemoccult II fecal occult blood test (Beckman Coulter, Fullerton, California). Tradeoffs between superior sensitivity and reduced specificity occur with high-sensitivity guaiac tests and fecal DNA, with other important uncertainties for fecal DNA. In settings with sufficient quality control, CT colonography is as sensitive as colonoscopy for large adenomas and colorectal cancer. Uncertainties remain for smaller polyps and frequency of colonoscopy referral. We did not find good estimates of community endoscopy accuracy; serious harms occur in 2.8 per 1000 screening colonoscopies and are 10-fold less common with flexible sigmoidoscopy.

Limitation: The accuracy and harms of screening tests were reviewed after only a single application.

Conclusion: Fecal tests with better sensitivity and similar specificity are reasonable substitutes for traditional fecal occult blood testing, although modeling may be needed to determine all tradeoffs. Computed tomographic colonography seems as likely as colonoscopy to detect lesions 10 mm or greater but may be less sensitive for smaller adenomas. Potential radiation-related harms, the effect of extracolonic findings, and the accuracy of test performance of CT colonography in community settings remain uncertain. Emphasis on quality standards is important for implementing any operator-dependent colorectal cancer screening test.

 

Archived: Introduction

Colorectal cancer ranks third in incidence and second in cause of cancer death for both men and women.1 Most cases of colorectal cancer occur in average-risk individuals (those without a family or predisposing medical history), and increasing age, male sex, and black race are associated with increased incidence.2 Black persons have the highest incidence of and mortality rates from colorectal cancer among all racial and ethnic subgroups.3-7 and nearly double the colorectal cancer-related mortality rate compared with other ethnic minorities.8

Colorectal cancer screening has been recommended by the U.S. Preventive Services Task Force (USPSTF) and many other organizations for more than 10 years.9 On the basis of evidence from multiple randomized, controlled trials (RCTs), a screening program with repeated annual or biennial guaiac fecal occult blood tests (FOBTs) and endoscopic follow-up of positive test results reduces colorectal cancer mortality; according to a recent update, colorectal cancer mortality was reduced 16% (CI, 10% to 22%) after 12 to 18 years.10 Extrapolating from trial evidence, clinical studies of test accuracy, and other supporting evidence, the USPSTF recognized flexible sigmoidoscopy (with or without FOBTs), colonoscopy, and double-contrast barium enema as other colorectal cancer screening options in 2002.11, 12 However, because colorectal cancer screening tests have potential harms, limited accessibility, or imperfect acceptability to patients, and no tests could be identified as superior in cost-effectiveness analysis.13, the USPSTF also recommended that choice among recommended methods for colorectal cancer screening to be individualized to patients or practice settings.14

Despite strong recommendations from the USPSTF and many others, serial national surveys document inadequate, slowly improving rates of colorectal cancer screening in the United States.15-20 In 2006, 60.8% of adults 50 years of age or older reported recent colorectal screening.20 Disparities in colorectal cancer screening exist, with lower rates of colorectal cancer screening in nonwhite and Hispanic populations16, 21, 22 and in areas with higher poverty rates.23

To increase the uptake of and benefits from recommended colorectal cancer screening, researchers have sought to improve the accuracy, acceptability, or accessibility of screening by introducing new tests or enhancing existing tests. However, the availability of additional options for colorectal cancer screening—including highly sensitive guaiac FOBT; fecal immunochemical testing; fecal DNA testing; and "virtual colonoscopy" approaches, such as computed tomographic (CT) colonography—has created uncertainty about what methods should be used for colorectal cancer screening in the general population.

To assist the USPSTF in updating its 2002 recommendation for colorectal cancer screening in average-risk adults age 50 years or older, we conducted a targeted systematic review primarily focused on evidence gaps or new evidence since the previous review. This approach updated what the USPSTF judged was the most important evidence for newer colorectal cancer screening tests and community-performed endoscopies, and it was supplemented by a companion decision analysis examining screening program performance and life-years gained by using different colorectal cancer screening tests, test intervals, and starting and stopping ages.24

Archived: Methods

Under guidance from the USPSTF, this targeted review addressed only the first 3 questions of the full evidence chain in the analytic framework (Figure 1). From our larger report,25 we report here the accuracy (one-time test performance characteristics) and potential harms of newer colorectal cancer screening tests (high-sensitivity FOBTs, fecal immunochemical tests, fecal DNA testing, and CT colonography) in screening populations (key questions 2b and 3b) and the accuracy and harms of screening colonoscopy and flexible sigmoidoscopy in the community setting (key questions 2a and 3a). In the full report, we discuss lack of new data on the mortality benefits of colorectal cancer screening beyond FOBT programs (key question 1); race-, sex-, and age-related issues in colorectal cancer screening; considerations of targeted screening recommendations; and suggested future research. Detailed methods are provided in the Appendix and Appendix Tables 12, and 3 and in the full report.25

Searches and Selection Process

In brief, we searched PubMed; Database of Abstracts of Reviews of Effects; Cochrane Database of Systematic Reviews; and the Institute of Medicine, National Institute for Health and Clinical Effectiveness, and Health Technology Assessment databases for recent systematic reviews (1999-2006) to support our review of all key questions.26 We found 11 existing systematic reviews for newer colorectal cancer screening tests (key question 2b). Using methods detailed in the Appendix, we selected 3 good-quality reviews of CT colonography27, 28 or fecal DNA testing29 to locate relevant primary studies; we supplemented these with additional MEDLINE and Cochrane Library searches from January 2006 through January 2008 to locate additional studies published after the end date of the searches. Because there were no good-quality relevant systematic reviews for reports on fecal immunochemical tests (key questions 2b and 3b), we searched MEDLINE and the Cochrane Library (1990-2008) and from 2000 to 2008 to locate studies of the harms of screening tests (key questions 3a and 3b) since the 2002 report.

Abstracts and articles were dual-reviewed against inclusion criteria (Appendix) and required agreement of 2 reviewers. Eligible studies reported on the sensitivity and specificity of colorectal cancer screening tests or on health outcomes. We excluded studies that did not address average-risk populations for colorectal cancer screening, unless an average-risk subgroup was reported. We excluded case-control studies of screening accuracy because these may overestimate sensitivity as a design-related source of bias,30 as recently demonstrated for FOBTs.31 To avoid biases related to reference standards, we excluded studies of test accuracy that incompletely applied a valid reference standard or used an inadequate reference standard.32 For CT colonography, we considered only technologies that were compared with colonoscopy in average-risk populations, used a multidetector scanner,27 and reported per-patient sensitivity and specificity. In all, we evaluated 3948 abstracts and 490 full-text articles (Figure 2).

Quality Assessment and Data Abstraction

Two investigators critically appraised and quality-rated all eligible studies by using design-specific USPSTF criteria33 supplemented by other criteria (Appendix). Poor-quality studies were excluded. One investigator abstracted key elements of included studies into standardized evidence tables. A second reviewer verified these data. We resolved disagreements about data abstraction or quality appraisal by consensus. Evidence tables and tables of excluded studies for each key question are available in the full report.25

Data Synthesis and Analysis

We report qualitative synthesis of the results for most key questions because of study heterogeneity. The performance of screening tests is preferentially described per person (sensitivity and specificity), supplemented by per-polyp analyses (miss rates). Sensitivity for large adenomas from 2 similar studies of CT colonography screening was combined by using the inverse variance fixed-effects model because no heterogeneity was detected on the basis of the Cochran Q test and the I2 statistic.34 Because of the stringency of our inclusion criteria for studies to estimate rates of endoscopy harms in the community practice setting (key question 3a), included studies were clinically homogeneous enough to pool. A random-effects logistic model was used to evaluate statistical heterogeneity, estimate pooled rates, and explore potential sources of variation for complications from study-level characteristics.35, 36 Model details and SAS PROC NLMIXED code are provided in the Appendix. Total serious adverse events required hospital admission (for example, perforation, major bleeding, severe abdominal symptoms, and cardiovascular events) or resulted in death. Results of exploratory analyses for potential sources of variation for pooled estimates are discussed in the full report, along with pooled estimates for individual complications, such as perforations.25

Role of the Funding Source

The Agency for Healthcare Research and Quality funded this work, provided project oversight, and assisted with internal and external review of the draft evidence synthesis but had no role in the design, conduct, or reporting of the review. The authors worked with 4 USPSTF members to develop the analytic framework, set the review scope, and resolve methodologic issues during the conduct of the review. The draft systematic review was reviewed by 8 external peer reviewers and was revised for the final version.

Archived: Results

Our results are organized by screening method rather than key question, with newer tests discussed first. More detailed results, including evidence tables for each key question, are available in the full report.25

Fecal Immunochemical Tests, Hemoccult SENSA, Fecal DNA, and CT Colonography (Key Questions 2b and 3b)

We evaluated 3 categories of newer fecal colorectal cancer screening tests (fecal immunochemical testing, high-sensitivity guaiac FOBT, and fecal DNA testing) and CT colonography. Among these, the largest body of fair- or good-quality evidence with which to evaluate performance of colorectal cancer screening tests in average-risk screening populations was for several different fecal immunochemical tests, followed by Hemoccult SENSA (Beckman Coulter, Fullerton, California), CT colonography, and fecal DNA testing.

Accuracy of Newer FOBTs

Although we found 9 fair- or good-quality cohort studies evaluating fecal immunochemical tests in 86,498 average-risk persons, these tests cannot be clearly analyzed as a class.37 Therefore, we grouped results by test type for 4 different tests (Table 1). Limited data suggest better detection of colorectal cancer and large adenomas with 2 to 3 days of sample collection for FOBTs than with 1 day of sample collection. With few exceptions, studies did not directly compare fecal immunochemical tests with each other or with regular or high-sensitivity Hemoccult testing.

Overall, fecal immunochemical tests had higher sensitivity for colorectal cancer (61% to 91%).38-46 than was reported for nonrehydrated Hemoccult II (25% to 38%) in another recent systematic review31 and in the only study of fecal immunochemical testing that also evaluated Hemoccult II.39 Estimated specificity varied across fecal immunochemical tests (91% to 98%), and, in most studies, specificity appears lower than the reported specificity of nonrehydrated Hemoccult II (98% to 99%).39 Sensitivity for advanced neoplasia or large adenomas was less commonly reported but ranged from 27% to 67% for fecal immunochemical tests.39, 40, 43-45 The sensitivity of nonrehydrated Hemoccult II for large adenomas has been estimated at 16% to 31%.31 The single study directly comparing HemeSelect and nonrehydrated Hemoccult II reported twice the sensitivity for polyps 10 mm or greater for HemeSelect (SmithKline Diagnostics, San Jose, California) (67% vs. 31%).39 Currently, U.S. Food and Drug Administration (FDA)-approved fecal immunochemical tests with fair- or good-quality studies of screening test performance are largely not available on the U.S. market. Of the 4 fecal immunochemical tests discussed here, few were both FDA approved and on the U.S. market at the time this article was written.

Hemoccult SENSA had higher sensitivity for colorectal cancer (64% to 80%) than would be expected for Hemoccult II but lower specificity (87% to 90%)38, 39 (Table 1). In direct comparisons, Hemoccult SENSA was less sensitive for colorectal cancer (64%) than was FlexSure OBT/Hemoccult ICT (82%) but more sensitive for large adenomas (41% vs. 30%). Hemoccult SENSA was more sensitive for colorectal cancer (79%) than HemeSelect (69%) but had similar sensitivity for large adenomas (69% vs. 67%, respectively). Hemoccult SENSA was less specific for colorectal cancer and for adenomas compared with both fecal immunochemical tests.38 More people would be referred for colonoscopy with Hemoccult SENSA than with fecal immunochemical tests because of 2- to 3-fold higher rates of positive test results with the former. A combination Hemoccult SENSA/FlexSure screening approach, in which the fecal immunochemical test was developed only if the guaiac-based test result was positive, had identical sensitivity and better specificity compared with Hemoccult SENSA alone (98.1% vs. 90.1%). These estimates provide relative rather than absolute sensitivity or specificity because patients with negative results underwent flexible sigmoidoscopy (or registry follow-up) only.

Accuracy of Fecal DNA Testing

Eligible fecal DNA screening studies were limited to a fair-quality large cohort study that used a multitarget fecal DNA panel test (the precommercial version of PreGen Plus, version 1 [Exact Sciences, Marlborough, Massachusetts], which tests for 21 DNA mutations in the K-ras, APC, and p53 genes, along with markers for microsatellite instability and long DNA) in average-risk patients undergoing colonoscopy,47 and a smaller cohort study that tested a single mutation of the K-ras gene.48 We will not further discuss the test for the single K-ras gene mutation because it showed zero sensitivity, testing positive in none of the 31 participants with advanced colorectal neoplasia, including 7 patients with invasive colorectal cancer.

Researchers compared a one-time application of PreGen Plus (version 1.0) with 3-card nonrehydrated Hemoccult II in a study that enrolled 5486 average-risk asymptomatic patients who were all to undergo colonoscopy47 (Table 1). Among the 4404 that adhered to all 3 tests, a subset (n = 2507; mean age, 69.5 years; 45% male; 87% white; 14% with a positive family history) was selected for fecal DNA testing on the basis of colonoscopic and histopathologic results.

Test performance for fecal DNA was compared with that for Hemoccult II in the selected subgroup; among these patients, 8.2% had positive results on the fecal DNA panel and 5.8% had positive Hemoccult II results. One-time fecal DNA testing was more sensitive for adenocarcinoma than was Hemoccult II (sensitivities of 51% [CI, 34.8% to 68.0%] and 12.9% [CI, 5.1% to 28.9%], respectively). Both fecal DNA testing and Hemoccult II had poor sensitivity for advanced carcinoma. Although specificity for minor polyps or no polyps did not differ between fecal DNA and Hemoccult II, power to detect a difference may have been limited because the full sample was not tested.

Serious Harms of Fecal Colorectal Cancer Screening

We found no studies addressing serious adverse effects from any type of fecal colorectal cancer screening tests. Risks are most likely related to false-positive test results and the associated risks from unnecessary colonoscopy screening.

Accuracy of CT Colonography

Although we located 7 fair- or good-quality cross-sectional studies49-55 examining a total of 4468 average-risk patients screened for colorectal cancer with both CT colonography and same-day colonoscopy, 3 of these50-52[[50-52 did not contribute to our estimates of CT colonography test performance because of study limitations described in our larger report.25 The 4 remaining studies discussed here examined CT colonography screening in 4312 average-risk patients (Table 2); 3 of these studies also estimated colonoscopy sensitivity.49, 53, 54

The 2 largest and most comparable and applicable studies were conducted by Pickhardt and colleagues49 and the American College of Radiology Imaging Network (ACRIN)55 and together represent 87% of patients. These 2 studies found that CT colonography was comparable to colonoscopy for detecting large adenomas (≥10 mm), but not necessarily for smaller adenomas (≥6 mm). Pooled sensitivity for large adenomas in these 2 studies was 92% (CI, 87% to 96%), with no statistical heterogeneity detected between the studies (I2 = 0%; P = 0.42). Point estimates for the sensitivity of CT colonography for smaller adenomas in ACRIN (78% [CI, 71% to 85%]) were 11% lower than for Pickhardt and colleagues' study (88.7% [CI, 82.9% to 93.1%]) and significantly lower than estimates for optical colonoscopy obtained by using an enhanced reference standard of segmental unblinding.49 In addition, although CIs for sensitivity for detecting smaller adenomas overlap with those for the sensitivity for larger adenomas within both studies, intervals are wide. We did not pool sensitivity estimates for smaller adenomas because the 2 studies had quite different results, which were also statistically heterogeneous. This finding suggests uncertainty about the true sensitivity of CT colonography for smaller adenomas. Of note, the sensitivity of CT colonography for at least 1 of the studies55 is predicated on CT colonography-detected lesions that were 5 mm or greater, although these would not be the basis for referral for colonoscopy. The authors report that using a radiologic threshold of 6 mm for CT colonography-detected lesions reduced the sensitivity for large adenomas to 88%; similar data to estimate the change in sensitivity for smaller lesions are not provided. Sensitivity estimates for large adenomas or tumors for the 5-mm threshold varied among radiologists (from 67% to 100%), with fewer than half of radiologists detecting 100% of the 1 to 13 large adenomas in the cases they read. One of 7 colorectal tumors was missed on CT colonography in 1 study55, whereas both colorectal tumors were detected by CT colonography in the other.49

Per-patient specificity of CT colonography for small or large adenomas varied between the 2 largest studies. One study that used segmental unblinding to clearly distinguish false-positive CT colonography findings from false-negative colonoscopy findings had statistically significantly worse specificity (79.6% [CI, 77.0% to 82.0%]) for lesions 6 mm or greater, compared with 96% specificity for lesions 10 mm or greater.49 In contrast, ACRIN reported similar specificity for lesions regardless of size, with better specificity (88% [CI, 84% to 92%]) for lesions 6 mm or greater than reported by Pickhardt and colleagues.55 We did not pool specificity estimates because between-study results were too different and were statistically heterogeneous. In the ACRIN study, 40% (CI, 33.5% to 46.3%) of patients with lesions 6 mm or greater detected on CT colonography had lesions 6 mm or greater detected on colonoscopy.

Sensitivity and specificity estimates from 2 smaller fair-quality studies comparing CT colonography with colonoscopy are less informative because these studies detected relatively few lesions and their primary purposes were 1) to examine the relative accuracy of 2-dimensional vs. 3-dimensional methods for displaying and reviewing CT colonography images and 2) to compare radiologist performance.53, 54 Thus, these studies do not provide overall results for the population but rather report subsets of data to compare readers or technologies. Results are generally consistent, with better sensitivity for larger (compared with smaller) lesions, no clear differences between 2- and 3-dimensional approaches (which was confirmed by ACRIN), and some degree of interreader variability (which seems exaggerated in these studies because of small numbers of lesions).

The pooled sensitivity estimates for large adenomas provided here might be considered best-case estimates because the studies had very low (<1%) rates of inadequate examinations, used standardized CT technologies, used fecal tagging and contrast-based luminal fluid opacification, and used a limited number of very experienced radiologists for all readings. In addition, we know little about the sensitivity of CT colonography for flat adenomas from these studies. In a related report from the study by Pickhardt and colleagues,56 the per-lesion sensitivity for flat adenomas 6 mm or greater (82.8%) was reported to be similar to the sensitivity for polypoid adenomas 6 mm or greater (86.2%). This determination, however, was based on a total of 29 flat adenomas 6 mm or greater, with flat polyps found in 52 of 1233 persons (4.9%).56

On the basis of a referral threshold of any polyp 6 mm or greater, these studies suggest that 1 in 3 to 1 in 8 persons screened with CT colonography would be referred for colonoscopy.

Serious Harms of CT Colonography

Few serious, procedure-related harms (for example, perforation, major events requiring medical attention) have been reported in 6 fair-quality cohort studies that addressed potential adverse effects with CT colonography screening.49, 54, 55, 57-59 Overall, the risk for perforation with screening CT colonography in asymptomatic persons seems very low, with no perforations reported in 2 studies of 14,238 screening CT colonographies55, 57 or in a study of 3120 CT colonographies.54 In 1 study, however, 1 person among 2531 persons undergoing both CT colonography and colonoscopy was hospitalized for bacteremia.55 Among 11,870 screening and diagnostic CT colonography examinations, researchers reported just 1 perforation in the subgroup of persons undergoing screening CT colonography, compared with 6 in the subgroup undergoing diagnostic CT colonography.59 Two small studies (n = 1587) did not report on perforation rates but did report that no major adverse events occurred.49, 58

Harms related to bowel preparations required for CT colonography, colonoscopy, or flexible sigmoidoscopy are considered in the larger report.25

Uncertain Effects of CT Colonography Screening

Uncertainties associated with CT colonography screening include potential long-term harms from CT colonography-related radiation exposure. In addition, because CT colonography produces images of structures outside the colon, the implications of extracolonic findings that occur with CT colonography screening—including potential benefits from early disease detection as well as harms from unnecessary medical testing and anxiety—are unclear.

We identified no studies that directly measured harms caused by low-dose radiation exposure from CT. However, existing models can indirectly estimate potential adverse effects for lifetime attributable risk for cancer by extrapolating the cancer-related risks at the range of effective radiation doses reported for CT colonography from existing risk models based on much higher radiation exposure. On the basis of 2 reviews, total radiation exposure with CT colonography ranges from 1.6 to 24.4 mSV for dual positioning (both supine and prone), with a median dose estimate of 8.8 mSv or 10.2 mSv per examination.60, 61 On the basis of the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VII phase 2 report findings.62, the National Research Council predicts that approximately 1 additional individual per 1000 would develop cancer (solid cancer or leukemia) from exposure to 10 mSv above background (according to the linear no-threshold model). Because of limitations in the data used to develop this model, these risk estimates are uncertain and could vary by a factor of 2 or 3.62 In addition, some organizations believe that the linear no-threshold model is an oversimplification that may overestimate the risk for malignancy.63

Extracolonic findings detected by CT colonography are common, occurring in 27% to 69% of persons screened with CT colonography (Appendix Table 4). We identified 9 studies (n = 12,557) that reported estimates of extracolonic findings in asymptomatic persons.49, 55, 64-70 In these studies, classification of extracolonic findings varied but generally considered 3 types of clinical significance: high (findings that require surgical treatment, medical intervention, or further investigation), moderate (findings that would not require immediate medical attention but would probably require recognition, investigation, or future treatment), and low (findings that would not require further investigation or treatment). These 3 categories generally map to the CT Colonography Report and Data System (C-RADS).71, as described elsewhere.25 Extracolonic findings of high clinical significance (for example, indeterminate solid organ masses or chest nodules, abdominal aortic aneurysms ≥3 cm, aneurysms of the splenic or renal arteries, or adenopathy >1 cm) occurred in 4.5% to 11% of asymptomatic populations.49, 65-67, 69, 70 Extracolonic findings of moderate clinical significance (such as renal calculi and small adrenal masses) were equally or more common and occurred in up to 27%.49, 64, 65, 67-70 Because all extracolonic findings of high significance, along with some moderate findings, would require medical follow-up, these have the potential for additional morbidity and cost, as well as potential benefit. Across studies, approximately 7% to 16% of persons undergoing CT colonography were recommended to have additional diagnostic evaluation for extracolonic findings.55, 64, 65, 67, 68, 70 Only a minority of these findings ultimately warranted definitive treatment (for example, repair of abdominal aortic aneurysm, resection of malignant lesions, or chemotherapy for metastatic lesions).64, 65, 68-70 Although these estimates provide important contextual information, they are limited by the available studies, which varied greatly in their ability to accurately assess follow-up and in the duration of follow-up, the longest of which was 2 years.

Colonoscopy and Flexible Sigmoidoscopy in Community Settings (Key Questions 2a and 3a)

Accuracy of Colonoscopy

Evaluating the accuracy of screening colonoscopy in average-risk participants, particularly in community settings, is challenging because of the lack of an independent gold standard and very few applicable studies. As detailed in the full report,25 we found no studies of miss rates after tandem screening colonoscopy in average-risk patients to fairly represent performance of community endoscopists, and no studies of repeated colonoscopy within 3 years after screening colonoscopy in a representative sample of average-risk community-based patients.

Researchers have used CT colonography screening studies already discussed49, 53, 54 to estimate the sensitivity of colonoscopy for colorectal cancer and for adenomas of various sizes detected using either CT colonography or colonoscopy. Two of these studies conducted CT colonography followed by colonoscopy with segmental unblinding to recheck CT colonography-located lesions not seen on first-pass colonoscopy;49, 53 1 of these provides the single best estimate for community performance of colonoscopy49 (Table 2). In this good-quality study of 1233 average-risk persons, colonoscopy by 1 of 17 experienced colonoscopists missed 10% of adenomas 6 mm or greater and 12% of adenomas 10 mm or greater. Sensitivity (per-person detection rate) of colonoscopy for adenomas 6, 8, or 10 mm or greater did not statistically significantly differ from sensitivity of CT colonography. Colonoscopy missed 1 of 2 colorectal lesions detected, whereas CT colonography detected both. In the second study using segmental unblinding, no colorectal cancer was detected in 96 average-risk patients using either test, and colonoscopy by 1 of 5 gastroenterologists missed 10% of polyps 6 mm or greater but no polyps 10 mm or greater. Colonoscopy was much less accurate in the third study of 452 asymptomatic, average-risk patients, detecting only 77% (20 of 26) of neoplasms 10 mm or greater and just 1 of 5 colorectal lesions detected by CT colonography.53 This study, however, evaluated the performance of more than 50 experienced endoscopists, whereas CT colonography was conducted by 3 very experienced radiologists.

Taken together, these data are insufficient to provide precise estimates of the sensitivity of colonoscopy in community settings, particularly for colorectal cancer detection, because of the small number of patients studied (n = 1781) and the relatively few lesions (7 total colorectal lesions). They do, however, confirm that colonoscopy misses some polyps and may also miss colorectal cancer.

Serious Harms from Colonoscopy

We found 17 fair- or good-quality, primarily prospective, studies evaluating clinically significant adverse events from screening colonoscopy conducted in predominantly asymptomatic persons.49, 55, 67, 77-85 Only 1 of these studies.81 was included in the 2002 systematic review for the USPSTF. Seven of these 16 studies were conducted in community settings.55, 73, 75, 77, 79, 80-83 Using a random-effects logistic model to pool data from the 12 studies (n = 57,742)49, 55, 73-76, 79, 80, 82-85 reporting this outcome, we found 2.8 total serious complications (including perforations, hemorrhage, diverticulitis, cardiovascular events, severe abdominal pain, and death) per 1000 procedures (CI, 1.5 to 5.2 per 1000 procedures; test for heterogeneity; P = 0.13) (Appendix Figure 1). When we limited the model just to the 7 studies conducted in the United States, serious complications were nonsignificantly reduced (2.5 per 1000 procedures [CI, 1.0 to 6.1 per 1000 procedures]). Because of reporting limitations, complication rates could not be calculated for colonoscopies with and without polypectomy. Only 3 of these 11 studies reported the proportion of colonoscopies in which polypectomies were performed—the proportions ranged from 41% to 68%.79, 80, 82 In these 3 studies, more than 85% of serious complications, perforations, and major bleeding incidents occurred during colonoscopies that required polypectomies. We could not estimate complications by age because of limitations in study reporting.

Accuracy of Flexible Sigmoidoscopy

We found no studies that estimated accuracy of flexible sigmoidoscopy in average-risk patients undergoing screening with both flexible sigmoidoscopy and colonoscopy. We report here the accuracy of screening with simulated flexible sigmoidoscopy reported in 6 large cohort studies of screening colonoscopy in a total of 14,938 average-risk patients.86-91 Elsewhere.25, we describe 3 studies—1 tandem flexible sigmoidoscopy study that reported adenoma miss rates92 and 2 prospective studies that reported distal advanced neoplasia or colorectal cancer on flexible sigmoidoscopy repeated 3 years after negative results on screening flexible sigmoidoscopy93, 94—that do not provide any greater precision than these estimates.

The estimated sensitivity of flexible sigmoidoscopy (using either biopsy or visual inspection to determine colonoscopy referral) for colorectal cancer throughout the entire colon was 58% to 75%, based on small numbers of colorectal lesions, with an estimated sensitivity of 72% to 86% for advanced neoplasia. Variations in these estimates are probably due to differences in examiner skill and the patient's risks for proximal lesions in the unexamined colon. These estimates are further limited because they simulate flexible sigmoidoscopy results by using colonoscopy examinations. This approach presumes that all lesions are detected if they are within the insertion depth for flexible sigmoidoscopy and ignores differences introduced through the more thorough bowel preparation used for colonoscopy or through colonoscopists' skill. The community performance of flexible sigmoidoscopy screening and its effect on health outcomes, including mortality from colo-rectal cancer, will become clearer after current RCTs are reported.

Serious Harms from Flexible Sigmoidoscopy

We found 8 fair- or good-quality studies that evaluated clinically significant adverse events from flexible sigmoidoscopy for colorectal cancer screening in an average-risk population.72, 74, 84, 85, 95-98 Only 1 of these studies was included in the previous 2002 review.72

Using a random-effects logistic model to pool data from the 6 studies72, 74, 84, 85, 95, 96 reporting this outcome (n = 126,985), we found 0.34 serious complication per 1000 procedures (CI, 0.06 to 1.9 per 1000 procedures; test for heterogeneity, P = 0.26) (Appendix Figure 2). Serious complications were defined the same as for screening colonoscopy but excluded complications from follow-up colonoscopy. Per protocol, all of these studies performed polypectomy during flexible sigmoidoscopy; based on 2 studies, polypectomies were conducted in 20% to 22% of flexible sigmoidoscopy examinations.72, 74 We could not estimate complications by age because of limitations in study reporting.

 

 

 

Archived: Discussion

Since 2002, research on colorectal cancer screening has grown substantially as researchers have investigated the accuracy of novel screening approaches and have continued examining already recommended approaches. As discussed in our full report,25 we found no new reports of the mortality impact of colorectal cancer screening (besides FOBT programs); however, results from several trials of flexible sigmoidoscopy that will report mortality effects are pending.84, 99, 101 In addition, although we found many studies addressing test performance of newer FOBTs, fecal DNA screening tests, or CT colonography,25 relatively few addressed average-risk screening populations and used minimally acceptable study designs and methods. Table 3 summarizes review findings about the performance and harms of new fecal screening tests, CT colonography, colonoscopy, and flexible sigmoidoscopy by key question, with newer tests reported first.

Recent guidance articulates evidence requirements to justify replacing a currently recommended diagnostic (or screening) test with a newer test in the absence of RCTs showing benefit;102, 103 this pertains to replacing existing colorectal cancer screening tests with newer ones. Accordingly, researchers should evaluate the comparative accuracy of newer and older tests by using the same reference standard as trials that showed treatment benefit in the same (or similar) patients representing the appropriate disease spectrum.103 If the newer test has increased sensitivity—with similar specificity and patient safety—or similar sensitivity but other advantages (for example, improved specificity, acceptability, or accessibility), studies of test accuracy alone may support substituting this test in the absence of trial data.103 However, when new tests offer tradeoffs between desirable and undesirable attributes (for example, improved sensitivity but reduced specificity), a decision analytic model or new research may be needed. When data on new tests are incomplete or uncertain, and the costs or consequences of making assumptions from such data are potentially severe, clinicians may require further research before acting.103

Fecal Screening Tests

As determined primarily through indirect comparisons, several fecal immunochemical tests had superior single-test sensitivity for colorectal cancer and possibly for advanced neoplasia compared with Hemoccult II. Fecal immunochemical tests had similar or somewhat lower specificity, suggesting that test choice might be important when considering substituting fecal immunochemical tests in a fecal screening program. For one quantitative fecal immunochemical test (Magstream, Fujirebio Inc., Tokyo, Japan), choice of positive cutoff values would allow programs to determine the appropriate tradeoff between improved sensitivity and specificity. Limited evidence suggested better test performance with 2- or 3-day sample collection than with 1-day collection. Ease of administration may work in favor of some fecal immunochemical tests,31 although their increased costs may reduce acceptability for payers. The relatively small increase in Medicare reimbursement for fecal immunochemical tests (exceeding those for Hemoccult II)104 may be affecting market availability. Not all well-studied fecal immunochemical tests were both FDA approved and on the U.S. market at the time this article was written.

On the basis of fewer data and less precise estimates, Hemoccult SENSA also had increased sensitivity for colorectal cancer compared with Hemoccult II but reduced specificity. Direct comparisons with fecal immunochemical tests were few, with mixed results for sensitivity and consistently lower specificity for Hemoccult SENSA. The tradeoffs from improved sensitivity with reduced specificity in a screening program of repeated testing is best evaluated through modeling.24

One study on screening test performance of the precommercial version of a multitarget fecal DNA test (PreGen Plus) showed improved sensitivity for colorectal cancer but not adenomas, similar or slightly reduced specificity, and higher positive rates compared with Hemoccult II.47 Test accuracy estimates for colorectal cancer were imprecise for both tests because of power, and sensitivity and specificity of Hemoccult II in this study were lower than generally reported in higher-quality studies.31, 105 In addition, this study's findings may not be generalizable to population screening because participants were relatively older (three quarters were >65 years of age, compared with screening beginning at age 50 years) and the version of PreGen Plus tested has been supplanted by other versions (1.1 and higher) for which there are no screening population studies (Table 3). Commercial availability of fecal DNA tests may be further affected by the recent FDA requirement for premarket review of this test, which was previously considered to be outside FDA jurisdiction.106, 107 Furthermore, in the absence of trial data or modeling, fecal DNA could be considered only as a substitute for an annual or biennial FOBT in established screening programs. This could be cost-prohibitive given the relative cost for fecal DNA compared with guaiac or immunochemical tests.104 Cost concerns may underlie recommendations by the manufacturer to repeat fecal DNA screening at 5-year intervals.108 Data on health outcomes are insufficient, however, to support this interval recommendation.109

Accuracy, Harms, and Uncertainties with CT Colonography

Computed tomographic colonography has been studied as a diagnostic test (for patients with symptoms) and, less frequently, as a screening test in average-risk asymptomatic patients. Recent publication of the ACRIN study has more than doubled the number of average-risk patients studied to determine the accuracy of CT colonography for colorectal cancer screening,55 with only 1 smaller screening study (n = 300) still pending.110 On the basis of published studies in 4312 average-risk screening patients, CT colonography screening by trained and experienced radiologists had sensitivity similar to that of colonoscopy for colorectal cancer and large adenomas (≥10 mm). However, estimates of sensitivity of CT colonography for smaller adenomas (≥6 mm) was more variable between studies (with point estimates of 78% and 88.7% and wide CIs) and was not clearly comparable to the sensitivity of colonoscopy for smaller adenomas. The health impact of potentially reduced sensitivity for smaller polyps is unclear.111 Specificity estimates for CT colonography were also quite variable between studies; for lesions 6 mm or greater, point estimates ranged from 79.6% to 88%.

Beyond issues of test accuracy, other uncertainties may affect considerations of whether this test is ready for widespread population screening. These include questions about potential harms from radiation exposure, uncertainty about extracolonic findings, uncertainty about test referral thresholds and repeat test intervals, and judgments about how the test performance seen in clinical studies will translate to the conduct of CT colonography screening examinations in community settings. Most important is how clinicians and policymakers value these remaining uncertainties and whether the costs or consequences of making assumptions from incomplete data are viewed as potentially severe, thus requiring further research before acting.103

Immediate procedure-related harms with CT colonography appear to be minimal. The risk for perforation with air insufflation is very low, particularly in asymptomatic persons undergoing screening. Uncertainty remains about delayed harms associated with CT-related radiation exposure, an area of growing concern with more widespread use of CT for diagnostics and screening.112 The estimate of 1/1000 excess lifetime tumors in a 50-year-old after a single CT colonography examination is uncertain and could vary 2- to 3-fold. Radiation-related cancer risks could decrease if newer technologies reduce average radiation exposure (that is, from 10 mSv to about 5 mSv).113 A recent survey of 22 institutions conducting CT colonography found a total median radiation dose per screening protocol of 5.6 mSv (range, 2.6 to 14.7 mSv).114 Thus, because radiation doses depend on factors associated with the technology used and with decisions by the technician,112 higher radiation exposure might persist in some settings. Even assuming a 10-fold lower risk (1/10,000 excess cancer risk), a recent modeling exercise115 found that lifetime CT colonography screening (starting at age 50 years and repeated every 10 years) produced 36/100,000 radiation-induced cases of cancer with 8 deaths, which offset some of the modeled mortality benefits from reductions in colonoscopy-associated complications.

Extracolonic findings that may require clinical follow-up occur relatively commonly (up to 1 in 4 asymptomatic persons undergoing CT colonography screening), with 7% to 16% clearly receiving recommendations for further diagnostic imaging tests or surgery.55, 67 Whether these extracolonic findings will ultimately provide additional benefit or harm to those undergoing CT colonography screening for colorectal cancer, and at what additional cost to the health care system, is unknown. A recent modeling study that attempted to address extracolonic findings found a net benefit,115 although the range of these findings was restricted to considering cancer and abdominal aortic aneurysms (reducing the estimated prevalence of extracolonic findings from <1% to at most 5% of the screened population). Other limitations and concerns about the assumptions underpinning this modeling exercise have been noted elsewhere.116

The referral threshold for colonoscopy (size of lesions detected by CT colonography) is largely based on expert opinion rather than clinical outcomes. Most, but not all,109 experts currently suggest colonoscopy referral for a polyp 6 mm or greater. This makes referral to colonoscopy relatively common, with as many as 1 in 3 persons, to as few as 1 in 8, referred after CT colonography (Table 2). An ongoing nonrandomized comparative study of colonoscopy and CT colonography screening is offering patients with only 1 or 2 polyps 6 to 9 mm in size on CT colonography the option of CT colonography surveillance instead of immediate colonoscopy, under an institutional review board-approved protocol.67, 117 Under this protocol, fewer patients (1 in 13) have been referred to colonoscopy, compared with referring all those with polyps 6 mm or greater (1 in 8). The safety of this approach is still being determined. Variability in polyp measurement due to differences among readers, CT measurement approaches, and viewing displays further complicates considerations of appropriate polyp size for colonoscopy referral after CT colonography examination.118-120

An important question for those considering implementing population colorectal cancer screening using CT colonography is whether test accuracy for this technology-dependent, operator-dependent test will be the same in nonresearch settings as in clinical studies. Studies on the accuracy of CT colonography have generally used an enhanced reference standard, which allows the separation of false-positive CT colonography results from false-negative colonoscopy results by reconciling differences with second-look colonoscopy. These studies have confirmed that colonoscopy and CT colonography miss adenomas and colorectal cancer, although reliable estimates of colonoscopy accuracy are limited by very small numbers of lesions. When considering the comparative accuracy between 2 operator-dependent technologies (CT colonography and colonoscopy), current studies are further limited by using designs that compared a larger number of experienced colonoscopists (5 to 50) to a much smaller number of experienced or very experienced radiologists (2 to 15).

As others have stated, "Accurate CT colonography with high sensitivity and specificity for polyps ≥ 6 mm in size depends on meticulous technique".67 Differences in the experience and training of radiologist readers has been cited as the major factor underlying discrepant test accuracy estimates for CT colonography in nonscreening populations.121 Radiologists in nonacademic settings who read a validated set of 15 CT colonographies exhibited considerable individual variability in accuracy (53% to 93%),122 consistent with our findings from 2 smaller CT screening studies comparing readers,53, 54 as well as from ACRIN, which used trained and certified readers.55 The challenges of adequately ensuring high-quality CT colonography readings are further illustrated by reports from ACRIN that half of the radiologists did not pass the initial certifying examination (after either 1.5 days of training or experience with ≥500 cases), although all did pass after further training.123 Clearly, specification, implementation, and monitoring of quality standards will be needed before widespread population screening with CT colonography. Activities are reported to be under way to upgrade quality metrics and training for CT colonography through the American College of Radiology.109

Little is known about relative patient preferences for CT colonography compared with colonoscopy in average-risk screening populations, and preferences may differ from those of high-risk or symptomatic patients undergoing diagnostic CT colonography. Some data suggest that average-risk patients may prefer CT colonography for convenience, and slightly more (49.8%) would prefer CT colonography for future screening compared with those preferring colonoscopy (41.1%).49 Issues about patient preferences will become particularly important once considerations of benefits, harms, and community accuracy are resolved. At that point, patient acceptability should also consider the 2-step process (CT colonography followed by referral colonoscopy as needed), with a second bowel preparation for colonoscopy potentially required. Same-day colonoscopy may make repeated bowel preparation unnecessary but requires coordination between radiology and gastroenterology services.124

Availability of accurate CT colonography screening examinations that do not require any (or full) bowel preparation could greatly influence patient preferences and willingness to be screened.125, 126

Accuracy and Harms with Colonoscopy and Flexible Sigmoidoscopy in Community Settings

Colonoscopy has presumed accuracy given its position in the diagnostic evaluation of patients screened by other colorectal cancer methods, although gastroenterologists have explicitly recognized that accuracy is highly dependent on the quality of the bowel preparation and endoscopic examination.127 Recent CT colonography studies using an enhanced standard of repeating colonoscopy examination for discordant colonoscopy-CT colonography findings have confirmed that screening colonoscopy can miss colorectal tumors as well as adenomas. Related data from tandem colonoscopy in diagnostic or high-risk screening populations suggest reasonably low miss rates for large adenomas (2.1% [CI, 0.3% to 7.3%]);128 similarly, new or missed colorectal tumors occurred in 3.4% of a population-based cohort (n = 12,487) who had previously undergone colonoscopy for any reason up to 3 years before a new diagnosis of colorectal cancer.129 Although available studies do not precisely estimate the risk for missed lesions with screening colonoscopy, all underscore the importance of quality initiatives for the performance of colonoscopy or any operator-dependent technological screening tool.127

Colonoscopy presents a higher risk for immediate harms than do other tests. Serious harms from community endoscopies are about 10 times more common with colonoscopy (2.8 per 1000 procedures) than with flexible sigmoidoscopy (3.4 per 10,000 procedures). The estimates for harms from flexible sigmoidoscopy, however, have much wider CIs. Age-specific harm rates were sought but could not be determined.

Limitations

We reviewed the accuracy and harms of newer colorectal cancer screening tests as potential replacements for currently recommended tests. The USPSTF commissioned a separate, simultaneous decision analysis comparing different colorectal cancer screening programs to consider tradeoffs in test accuracy, repeated screening, and starting and stopping ages. Because of the targeted nature of this review, we did not formally update or address test acceptability (preferences, costs, adherence) issues; however, the importance of these issues for new technologies, such as CT colonography, may be considered as secondary to establishing the accuracy, harms, and community performance of the screening tests.

 

Archived: Conclusion

Some newer fecal screening tests with better sensitivity and similar specificity are reasonable substitutes for Hemoccult II testing to improve annual or biennial fecal screening programs for colorectal cancer. Modeling can help determine tradeoffs in fecal tests with improved sensitivity but reduced specificity and to compare results from screening programs. Colorectal cancer screening with CT colonography in average-risk populations is likely to detect larger adenomas and colorectal cancers as well as colonoscopy does, but it is not clear that CT colonography is as sensitive for smaller adenomas (≥6 mm) or what proportion of positive CT colonography results will be false positive. We did not evaluate the clinical benefit of detecting smaller polyps in this report. In addition, uncertainties about potential radiation-related harms, the effect of extracolonic findings, and test performance in community settings still remain. Given potential harms and observed variability in test accuracy, emphasis on quality standards for implementation of any operator-dependent colorectal cancer screening tests appears prudent. Considerations about colorectal cancer screening are affected by its rapidly evolving clinical science base, by the ongoing evolution of colorectal cancer screening technologies, and by a marketplace that continues to change. Thus, frequent reconsideration of available evidence and updating of recommendations is warranted.

Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Archived: Copyright and Source Information

For information on reprinting, contact Randie Siegel, Associate Director, Office of Communications and Knowledge Transfer, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850.

Requests for linking or to incorporate content in electronic resources should be sent via the USPSTF contact form.

 

Archived: Acknowledgement

The authors thank the following peer reviewers for the evidence report (alphabetical)—James Allison, MD, Carrie Klabunde, PhD, Ted Levin, MD, Perry Pickhardt, MD, Margaret Piper, PhD, MPH, David Ransohoff, MD, Robert Smith, PhD, and Steve Woolf, MD, MPH; Oregon Evidence-based Practice Center staff—Kevin Lutz, MA, Taryn Cardenas, BA, Rebecca Newton-Thompson, MD, MPH, Elizabeth O'Connor, PhD, Mark Helfand, MD, MS, MPH, and Daphne Plaut, MLS; and Centers for Disease Control and Prevention staff—Laura Seeff, MD.

 

Archived: Appendix: Detailed Methods

Under guidance from the USPSTF, we created and received USPSTF approval for an analytic framework and key questions adapted from the 2002 USPSTF report.130 The scope of this targeted review differed from the 2002 USPSTF report in several ways:

  1. We did not update the direct evidence that standard FOBT screening is effective in improving health outcomes, except in addressing longer-term follow-up from the original trials included in the 2002 report; this evidence was considered established for the 2002 and was foundational for the last recommendation.
  2. We did not update evidence on colorectal cancer screening methods not recommended after the last review (such as digital rectal examination) or omitted from this review at the workplan stage by the USPSTF because of poor test performance characteristics (such as double-contrast barium enema). A single study (n = 580) from the previous 2002 evidence report found that double-contrast barium enema used as a surveillance method after adenomatous polypectomy (with comparison to colonoscopy as the gold standard) showed a sensitivity of only 48% (CI, 24% to 67%) for polyps larger than 10 mm. A more recent study in a high-risk screening and diagnostic evaluation population comparing double-contrast barium enema to both optical and CT colonoscopy showed similarly low sensitivity estimates for large polyps.131 Given its confirmed low sensitivity for the targets of screening (lesions ≥10 mm), double-contrast barium enema as a primary colorectal cancer screening test was removed from the review.
  3. Systematic review of the adherence, acceptability, and feasibility the screening tests was not part of this updated report. Similarly, the USPSTF judged that a thorough review of cost-effectiveness analyses was beyond the scope of our review, particularly because the USPSTF was conducting a simultaneous decision analysis.24 The decision analysis focused on projected benefits to a cohort that began colorectal cancer screening at age 40 years or later for different screening strategies, different beginning and ending ages, and different intervals for rescreening after a normal test result, with varying screening test adherence.24 These 2 reports were used together by the USPSTF to make its updated recommendation on colorectal cancer screening, and affected the scope of our updated evidence review.

Data Sources and Searches

We first searched PubMed, Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews, Institute of Medicine, National Institute for Health and Clinical Excellence, and Health Technology Assessment databases for recent systematic reviews (1999-2006) for all key questions. We also searched the National Guideline Clearinghouse™, Institute of Medicine, and National Institute for Clinical Evidence Web sites for relevant reports.

For each key question, we used already synthesized literature to identify all appropriate primary studies to the extent possible, supplementing with new literature searches corresponding with the end-of-search windows of relevant good-quality systematic reviews and meta-analyses. We developed literature search strategies and terms for each key question,25 with search dates guided by existing systematic reviews (including the 2002 UPSPTF report) and the development of screening technology.

We conducted 5 separate literature searches, 1 for each key question (except that we combined searching for harms for key questions 3 and 3b, but conducted 2 separate combined harms searches) in both MEDLINE and the Cochrane Central Register of Controlled Trials. Although the searches were specifically designed for a particular key question, all abstracts were reviewed for inclusion in all key questions. All searches covered reports published through January 2008. For all key questions, we supplemented literature searches by reviewing bibliographies of relevant articles (including systematic reviews) and considering studies recommended by experts during and after peer review.

For key question 2a (accuracy of flexible sigmoidoscopy and colonoscopy), we found no systematic reviews conforming to our inclusion and exclusion criteria more recent than the 2002 USPSTF review and therefore searched MEDLINE and the Cochrane Library from January 2000 through January 2008 for primary literature.

Key question 2b (test performance characteristics of newer screening tests) covered 3 tests: CT colonography, fecal immunochemical tests, and fecal DNA tests. We found 11 systematic reviews relevant to newer colorectal cancer screening tests: 6 of CT colonography screening,27, 28, 132-135 3 of fecal DNA screening,29, 136, 137 and 2 of fecal immunochemical screening tests.31, 37 On the basis of their use of comprehensive search strategies, recent search dates (last search date at least within the last 3 years or no older than 2005), and use of quality assessment of articles as quality indicators, we selected 3 reviews (2 of CT colonography27, 28 and 1 of fecal DNA29 to substitute for a portion of the comprehensive search strategy necessary to locate primary studies for key question 2b.26 We searched MEDLINE and the Cochrane Library for additional primary studies for CT colonography and for fecal DNA (January 2006 through January 2008) beginning after the latest systematic review search date. We considered all studies examining CT colonography screening in average-risk patients from the selected reviews,27, 28 supplemented by studies in average-risk patients located through our literature search; as a final check, we examined the included studies in other relevant systematic reviews of CT colonography. No additional eligible studies were identified. Although we found several reviews of fecal immunochemical tests (key questions 2 and 3b), none met our standards for methods and reporting. We therefore searched MEDLINE and the Cochrane Library from 1990, when these tests began to be described, through January 2008. We checked our search results against 2 systematic reviews located during our review process to supplement with any potentially relevant studies not already identified.37, 37

For key questions 3a and 3b (harms of screening tests), we found no systematic reviews more recent than the 2002 USPSTF review and therefore searched MEDLINE and the Cochrane Library from January 2000 through January 2008 and coded abstracts from both approaches.

Study Selection

In total, we evaluated 3948 abstracts and 490 full-text articles. Abstracts and articles were reviewed against specified inclusion criteria (see below) and required agreement of 2 reviewers. Eligible studies reported on the performance of colorectal cancer screening tests (sensitivity and specificity) or health outcomes. We excluded studies that did not address average-risk populations for colorectal cancer screening, unless an average-risk subgroup was reported. We excluded case-control studies of screening accuracy because these may overestimate sensitivity as a design-related source of bias,30 a problem recently demonstrated clearly for FOBTs.31 To avoid biases related to reference standards, we excluded studies of test accuracy that incompletely applied a valid reference standard or used an inadequate reference standard.32 For CT colonography, we considered only technologies that were compared against colonoscopy in average-risk populations, used a multidetector (not single-detector) scanner,27 and reported per-patient sensitivity and specificity.

Quality Assessment and Data Abstraction

Two investigators critically appraised and quality-rated all eligible studies by using design-specific USPSTF criteria (see below)33 supplemented by National Institute for Clinical Excellence138 and Oxman and Guyatt139 criteria for systematic reviews and QUADAS criteria for diagnostic accuracy studies.140 Only good-quality systematic reviews were used as sources for primary articles, and all poor-quality studies were excluded from the review. One investigator abstracted key elements of all included studies into standardized evidence tables. A second reviewer verified these data. Disagreements about data abstraction or quality appraisal were resolved by consensus. Evidence tables and excluded studies tables for each key question are available in the full report.25

Data Synthesis and Analysis

We primarily report qualitative synthesis of the results for most key questions because of study heterogeneity. Results of key questions 2b and 3b were judged to be too heterogeneous in terms of populations, settings, and study designs for meta-analysis and were therefore qualitatively synthesized. The performance of screening tests is preferentially described per person (sensitivity and specificity), supplemented by per-polyp analysis (miss rates). Ninety-five percent CIs are reported when available.

Because of the stringency of our inclusion criteria for key question 3a (complications of endoscopy), which focused on estimates of harms in the community practice setting, the studies we included were thought to be clinically homogenous enough to allow pooling of complication rates. Meta-analysis was performed to estimate combined complication rates for major or serious bleeding, perforation, and total serious adverse events that require hospital admission or result in death, including perforation, major bleeding, severe abdominal symptoms, and cardiovascular events. Several studies reported that their patients experienced no adverse events, and therefore we used a logistic random-effects model35, 36 to include studies without any adverse events and estimate the combined complication rates. The model was described briefly as follows.

Suppose that there are i = 1, ..., n studies and number of complications and total procedures are xi and ni for study i. Denote that the complication rate from each study is pi, then we have

xi ~ binomial (ni, pi)
log(pi / 1 - pi) = β0 + μi
μi ~ N(0, τ2)

where μi is the random effects across studies and τ2 estimates the heterogeneity among studies on the logit scale. The combined complication rate, pcom, would be estimated by

pcom = exp(β0) / 1 + exp(β0)

This model allows inclusion of studies with no adverse events, and the random effects incorporate variation among studies into the combined estimate. A P value less than 0.05 for τ2 is considered to represent statistically significant heterogeneity.

Exploratory meta-regressions were conducted by using logistic random-effects models to examine the association of important study-level characteristics: study design, study setting by country, and population characteristics, including age range, and indication for endoscopy with complication rate. To do this, we need to add only one more term to equation2 of the logistic random-effects model:

log(pi / 1 - pi) = β0 + β1zi + μi

where zi represents any study-level characteristics from study i, and the association of this study characteristic with complication rate is investigated through β1.

The analysis was performed by using the NLMIXED procedure in SAS software, version 9.1 (SAS Institute Inc., Cary, North Carolina), with the code listed in Appendix Table 3.

Review Oversight and Peer Review

The Agency for Healthcare Research and Quality (AHRQ) funded this work, provided project oversight, and assisted with internal and external review of the draft evidence synthesis but had no role in the design, conduct, or reporting of the review. The authors worked with 4 USPSTF liaisons at key points throughout the review process to develop and refine the analytic framework questions, set the review scope, and resolve methodologic issues during the conduct of the review. A draft of the evidence synthesis was reviewed by 8 experts, including experts in the fields of gastroenterology and radiology, and several experts who have written systematic evidence reviews on one or more aspects of colorectal cancer screening.

 

 

Archived: Figure 1. Analytic Framework and Key Questions (KQs)

Select Text Description below for details

Text Description.

Figure 1 depicts the analytic framework for this review. The text at left-hand side of the figure reads "Adults age ≥50 y, average risk" and arrows point from it to three circles labeled 1, 2, 3 to denote these Key Questions (KQs).

An arrow points from KQ1 to a text box that reads: "Decreased colorectal cancer mortality. Decreased all-cause mortality."

An arrow points from KQ2 to a series of text boxes that read:

  • FOBT.
  • Flexible sigmoidoscopy.
  • FOBT + flexible sigmoidoscopy.
  • Colonoscopy.
  • CT colonography.
  • Fecal tests; High-sensitivity FOBT; Immunochemical DNA

Arrows point collectively from these boxes to three text boxes that read:

  • Colorectal cancer diagnosis.
  • Adenomatous polyp removal.
  • Negative screening.

A line leads from "Colorectal cancer diagnosis" through a circle labeled 4 (Colorectal cancer treatment); the line then divides into two arrows that point to the text box that reads: "Decreased colorectal cancer mortality. Decreased all-cause mortality" and to a circle labeled 5. An arrow points from KQ5 to an oval that reads "Harms of treatment."

A line leads from "Adenomatous polyp removal" through a circle labeled 6 (Surveillance); the line then divides into two arrows that point to the text box that reads: "Decreased colorectal cancer incidence" and to a circle labeled 7. An arrow points from KQ7 to an oval that reads "Harms of surveillance."

A line leads from "Negative screening" through a circle labeled 8; the line then becomes an arrows that points back to KQ2.

An arrow points from KQ3 to a oval that reads: "Harms of screening."

KQ1: What is the effectiveness of the following screening methods (alone or in combination) in reducing mortality from colorectal cancer? a. Flexible sigmoidoscopy, b. Colonoscopy, c. Computed tomographic (CT) colonography, d. Fecal screening tests: i. High-sensitivity guaiac fecal occult blood test (FOBTs); ii. Fecal immunochemical test; iii. Fecal DNA test.

KQ2a: What are the sensitivity and specificity of 1) colonoscopy and 2) flexible sigmoidoscopy when used to screen for colorectal cancer in the community practice setting?
KQ2b: What are the test performance characteristics of 1) CT colonography and 2) fecal screening tests (as listed in KQ1d) for colorectal cancer screening, as compared to an acceptable reference standard?
KQ3a: What are age-specific rates of harm from colonoscopy and flexible sigmoidoscopy in the community practice setting?
KQ3b: What are the adverse effects of newer tests, including 1) CT colonography and 2) fecal screening tests (as listed in KQ1d)?

Archived: Figure 2. Study Selection

Select Text Description below for details

 

Text Description.

Figure 2. Study Selection (Text Description)

Figure 2 depicts a study flow diagram. The text reads:

Abstracts reviewed from searches (n = 3948)
Total articles reviewed from searches (n = 398)
Total articles reviewed from outside sources (n = 92)
Total articles reviewed from searches and outside sources (n = 490)

  • Articles reviewed for KQ1 (n = 41)
    • Articles excluded for KQ1 (n = 32):
      Article covered by included SER: 1
      Does not report appropriate outcomes: 13
      Study design: 8
      Quality: 1
      Study relevance: 3
      Population: 1
      Setting: 1
      Out of scope: 1
      Precedes search period: 3
    • Articles included for KQ1 (n = 9):
      4 studies
  • Articles reviewed for KQ2a (n = 76)
    • Articles excluded for KQ2a (n = 62):
      Study design: 21
      Setting: 3
      Population: 13
      Relevance: 14
      Quality: 3
      Outcomes: 7
      Did not include specific screening test: 1
    • Articles included for KQ2a (n = 14):
      9 studies in 11 articles
      3 reported miss rates of flexible sigmoidoscopy
  • Articles reviewed for KQ2b (n = 216)
    • Articles excluded for KQ2b (n = 194):
      Abstract only: 2
      Did not answer primary question: 4
      Did not include 1 of the specific screening tests: 4
      Did not repost necessary outcomes: 14
      Duplicative review content: 2
      Population: 87
      Study quality: 6
      Study design: 49
      Relevance: 2
      Inadequate application of of reference standard: 15
      Not an original study: 1
      Source document: 8
    • Articles included for KQ2b (n = 22):
      21 articles in 20 studies
      1 SER
  • Articles reviewed for KQ3a (n = 164)
    • Articles excluded for KQ3a (n = 142):
      Relevance: 16
      Design: 37
      Setting: 51
      Population: 24
      Outcomes: 7
      Quality: 6
    • Articles included for KQ3a (n = 22):
      21 studies
  • Articles reviewed for KQ3b (n = 35)
    • Articles excluded for KQ3b (n = 27):
      Relevance: 3
      Design: 16
      Population: 3
      Outcomes: 3
      Screening tests: 1
      Quality: 1
    • Articles included for KQ3b (n = 8):
      6 studies
      2 SERs on radiation

KQ = key question; SER = standardized evidence review. For list of key questions, go to legend for Figure 1.

Archived: Table 1. Summary of Newer Fecal Test Studies

Table 1. Summary of Newer Fecal Test Studies

Study, Year (Reference); Patients, n; Study Quality Gold Standard Additional FOBT Tested or Threshold for Occult Blood Detection, ng/mL Duration of
Fecal Sample Collection, d
Magstream (Fujirebio, Tokyo)
Morikawa et al., 200544; 21,805; fair Colonoscopy for all patients 20 1
Launoy et al., 200542; 7421; fair Registry follow-up for screen-negative patients; colonoscopy for screen-positive patients >20
>50
>75
2
Allison et al., 199639; 8104; fair Registry follow-up for screen-negative patients; colonoscopy for screen-positive patients HemeSelect (Magstream)
Hemoccult SENSA
Hemoccult SENSA/HemeSelect
Hemoccult II
3
OC-Hemodia (Eiken Chemical Co., Tokyo)
Cheng et al., 200240; 7411; fair Colonoscopy for all patients  
Itoh et al., 199641;
27 860; fair
Registry follow-up for screen-negative patients; colonoscopy for screen-positive patients   1
Levi et al., 200743; fair Colonoscopy for all patients   3
FlexSure OBT (Hemoccult ICT, Beckman Coulter, Fullerton, California)
Allison et al., 2007a 38; 5841; good Colonoscopy for screen-positive patients or flexible sigmoidoscopy for screen-negative patients FlexSure
Hemoccult SENSA
FlexSure/Hemoccult SENSA
3
Monohaem (Millipore, Billerica, Massachusetts)
Nakama et al., 199945; 4611; fair Colonoscopy for all patients   1
2
3
Nakama et al., 199646,b; 3365; fair Registry follow-up for screen-negative patients; colonoscopy for screen-positive patients 1-y follow-up
2-y follow-up
3-y follow-up
1
Faecal DNA
Imperiale et al., 200447; 4404; fair Colonoscopy for all patients, but test accuracy limited to those selected for fecal DNA testing Fecal DNA testing done only in subsample based on histopathologic and colonoscopic results (n = 2507)
Hemoccult II
Whole-stool (30-g) sample

3

Table 1 (continued)

Study, Year (Reference); Patients, n; Study Quality Test Positivity Rate (%) Sensitivity (95% CI), % Specificity, % FDA Approved Available in U.S. Market
Magstream (Fujirebio, Tokyo)
Morikawa et al., 200544; 21 805; fair 5.6 CRC: 65.8
Advanced neoplasia: 27.1
Adenoma ≥ 10 mm: 20.0
CRC: 94.6
Advanced neoplasia: 95.1
Adenoma ≥ 10 mm: NR
No No
Launoy et al., 200542; 7421; fair 5.8

3.1

2.0

CRC: 85
Advanced neoplasia: NR
CRC: 67.8
Advanced neoplasia: NR
CRC: 61
Advanced neoplasia: NR

CRC: 94
Advanced neoplasia: NR
CRC: 97
Advanced neoplasia: NR
CRC: 98
Advanced neoplasia: NR
No No
Allison et al., 199639; 8104; fair

5.9

13.6

3.0

2.5

CRC: 68.8
Polyp ≥10 mm: 66.7
CRC: 79.4
Polyp ≥10 mm: 68.6
CRC: 65.6
Polyp ≥10 mm: 50.0
CRC: 37.1
Polyp ≥10 mm: 30.8
 
CRC: 94.4
Polyp ≥10 mm: 95.2
CRC: 86.7
Polyp ≥10 mm: 87.5
CRC: 97.3
Polyp ≥10 mm: 97.9
CRC: 97.7
Polyp ≥10 mm: 98.1

Yes

Yes



Yes

No

Yes



Yes

OC-Hemodia (Eiken Chemical Co., Tokyo)
Cheng et al., 200240; 7411; fair 9.2 CRC: 87.5
Advanced neoplasia: 48.4
CRC: 91.0
Advanced neoplasia: 91.3
Yes
(OC-Auto Micro 80,
Polymedco, Cortlandt
Manor, NY)
Yes
Itoh et al., 199641; 27,860; fair 5.3 CRC: 86.5 CRC: 94.9 No No
Levi et al., 200743; fair 18.8 CRC: 66.7
Advanced neoplasia: 55.6
CRC: 83.1
Advanced neoplasia: 91.9
No No
FlexSure OBT (Hemoccult ICT, Beckman Coulter, Fullerton, California)
Allison et al., 2007a 38; 5841; good

3.2

10.1

2.1

CRC: 81.8
Adenoma ≥ 10 mm: 29.5
CRC: 64.3
Adenoma ≥ 10 mm: 41.3
CRC: 64.3
Adenoma ≥10 mm: 22.8
CRC: 96.9
Adenoma ≥ 10 mm: 97.3
CRC: 90.1
Adenoma ≥10 mm: 90.6
CRC: 98.1
Adenoma ≥10 mm: 98.4
Yes

Yes
Yes

Yes
Monohaem (Millipore, Billerica, Massachusetts)
Nakama et al., 199945; 4611; fair

NR

NR

NR

CRC: 55.6
Adenoma: 30.1
CRC: 83.3
Adenoma: 50.7
CRC: 88.9
Adenoma: 54.8

CRC and adenoma: 97.1

CRC and adenoma: 96.0

CRC and adenoma: 93.9

Yes No
Nakama et al., 199646,b; 3365; fair 4.7 CRC: 90.9
CRC: 83.3
CRC: 71.4
CRC: 95.6 Yes No
Faecal DNA
Imperiale et al., 2004[47]]; 4404; fair

8.2

5.8

 

CRC: 51.6 (34.8-68.0)
Advanced adenoma: 15.1
(12.0-19.0)
CRC: 12.9 (5.1-28.9)
Advanced adenoma: 10.7
(8.0-14.0)
 
Minor polyps: 92.4
No polyps: 94.4
Minor polyps: 95.2
No polyps: 95.2
 

No

Yes

Yes

Yes

CRC = colorectal cancer; FDA = U.S. Food and Drug Administration; FOBT = fecal occult blood testing; NR = not reported.

a. Left-sided tumors only.
b. Sensitivity and specificity of small adenomas or polyps of unknown size are found in the full evidence table25.

Archived: Table 2. Accuracy of Computed Tomographic Colonography and Estimated Rates of Referral to Colonoscopy

Variable Colonoscopy: Pickhardt et al., 200349 CT Colonography
Pickhardt et al., 200349
CT Colonography
Johnson et al., 200855
CT Colonography
Kim et al., 200754,a
CT Colonography
Johnson et al., 200753,a
Study aim To evaluate performance characteristics of CT colonography screening To assess the accuracy of CT colonography in multicenter screening setting To compare 3D vs. 2D interpretation of CT colonography To compare 3D vs. 2D interpretation of CT colonography using 2.5-mm and 1.25-mm slice thickness
Patients, n 1233 2531 96 452
Population 50-79 y; 41% female ≥50 y; 54% female 40-76 y; 42% female 41-82 y; 44% female
CT Colonography   Flythrough 3D imaging with 2D correlation of abnormality (Viatronix V3D 1.2, Stony Brook, New York); stool tagging; luminal fluid tagging; 6 trained radiologists Randomly assigned primary 2D or 3D flythrough analysis (5 software packages used); stool tagging; luminal fluid tagging; 15 trained and certified radiologists 3D virtual colon dissection (Perspective Filet View) and 2D display (Rapidia); intravenous contrast agent for extracolonic findings; 2 very experienced radiologists 3D virtual dissection (Voxtool 5.4.46, GE Healthcare, Milwaukee, Wisconsin); no contrast agent; 3 very experienced radiologists
Reference standard Same-day colonoscopy by 1 of 17 experienced colonoscopists using segmental unblinding   Same-day blinded colonoscopy conducted or supervised by unspecified number of experienced endoscopists, with unblinded second colonoscopy for CT-detected lesions ≥10 mm not detected on initial colonoscopy Same-day colonoscopy by 1 of 5 experienced gastroenterologists using segmental unblinding Same-day videotaped colonoscopy conducted or supervised by 1 of 50 experienced endoscopists; repeat colonoscopy in 6 cases of large lesion on CT colonography
Study quality Good: Use of enhanced reference standard allows distinguishing false-positive CT colonography results from false-negative optical colonoscopy results; interobserver agreement checked on subset of cases Fair: Colonoscopy reference standard by community operators without clear quality guidelines; incomplete follow-through on second-look colonoscopies (15 of 27); test performance based on 5-mm CT colonography threshold Fair: Retrospective analysis comparing types of CT colonography and reader reliability Fair: Limited power because of multiple analyses comparing readers, displays, and collimation thicknesses; colonoscopy reference standard not high quality
Applicability Predominantly average-risk screening population, 3% with family history; may represent best-case estimates because of technology used and limited number of experienced readers Multicenter study of primarily average-risk participants (9% with family history; 2% with personal history of polyps or cancer); use of 15 trained, qualified readers, with range of sensitivity (67%-100%) for large adenomas and CRC Uncertain because of setting, small study size, limited number of very experienced radiologists compared with endoscopists Small number of more skilled radiologists; unusually high yield of CRC and low prevalence of polyps compared with other screening populations, possibly due to not excluding patients with previous colonic resections
Sensitivity (per patient) (95% CI), % Range of 3D and 2D Range of 3D and 2D
CRC 1 of 2 CRC cases detected 2 of 2 CRC cases detected 6 of 7 CRC cases detected None detected 5 of 5 CRC cases detected
Adenoma ≥10 mm 87.5 (74.8-95.3) 93.8 (82.8-98.7) 90 (84-96)b 100c 50-83
Adenoma ≥6 mm 92.3 (87.1-95.8) 88.7 (82.9-93.1) 78, (71-85)b 59-77c NR
Specificity (per patient) (95% CI), %
Lesions ≥10 mm NA 96.0 (94.8-97.1) 86 (81.3-90.0) 99-100 97-99

Lesions ≥6 mm

NA 79.6 (77.0-82.0) 88 (84.0-92.0) 89-99 NR
Referral for colonoscopy
Lesions ≥10 mm NA 1 in 13 NR 1 in 10 Not calculatedd
Lesions ≥6 mm NA 1 in 3 1 in 6-8e 1 in 5 Not calculatedd

2D = 2-dimensional; 3D = 3-dimensional; CRC = colorectal cancer; CT = computed tomography; NA = not applicable; NR = not reported.
a. Point estimates and CIs are calculated from multiple measurements provided in the studies. Methods can be found in reference25.
b. Detection of adenoma or cancer in Johnson et al.55 on CT colonography- detected lesions 5 mm or greater.
c. Detection of polyp in Kim et al.54.
d. Polyp prevalence significantly different from those reported in other similar studies.
e. Range of estimates: 1 in 6 referred for colonoscopy is based on the referral threshold for 5-mm lesions on which sensitivity and specificity calculations are based; 1 in 8 is based on a colonoscopy referral threshold for lesions ≥6 mm.

Archived: Table 3. Summary of Results

Table 3. Summary of Results*

Key Question and Test Number of Studies and Study Design Limitations Consistency
What are the test performance characteristics of CT colonography and fecal screening tests (e.g., high-sensitivity guaiac FOBT, FIT, or fecal DNA tests) for CRC screening as compared to an acceptable reference standard? (Key question 2b)
Fecal tests 11 total studies

FIT

9 cohort studies of test accuracy Cannot clearly be analyzed as a class; many different tests,with few studies per test. Performance for all but 1 FIT was reported qualitatively at a single cut-point rather than quantitatively (i.e., across multiple cut-points). Several studies used registry follow-up for screen-negative patients, probably overestimating sensitivity. Estimates of sensitivity and specificity show variability within each test, possibly because of different collection methods or reference standard applied.

High-sensitivity guaiac

2 cohort studies of test accuracy 2 comparative studies, 1 using different reference standards for different tests. 1 study provides estimates for left-sided lesions only.

Fecal DNA

2 cohort studies of test accuracy 1 study for each of 2 approaches. Only fecal DNA panel had any sensitivity for CRC; this test has been replaced by another, presumably upgraded test. Not applicable.
CT colonography 4 cohort studies of test accuracy Variability between readers limits studies' ability to provide precise estimates of CT colonography sensitivity for lesions <10 mm. Specificity estimates are somewhat uncertain. Health implications of uncertainties in test performance are unclear. 1 study (n = 1233) using 3D flythrough endoluminal imaging and 1 study (n = 2531) using 3D flythrough or 2D imaging represent most (87%) patients studied and use comparable approaches, including oral contrast agents for fecal tagging and luminal fluid opacification.
What are the adverse effects of CT colonography and/or fecal screening tests (high-sensitivity FOBTs, FIT, and fecal DNA)? (Key question 3b)
Fecal tests - - -
CT colonography 4 prospective cohort studies, 2 retrospective cohort studies Unclear clinical significance of asymptomatic perforations visualized on CT. No direct evidence of harms from low-dose ionizing radiation from CT studies. Uncertain impact of possibly clinically significant extracolonic findings found in 5%-27% of CT colonography examinations, based on 9 studies (n = 12,557). 4 prospective studies included predominantly asymptomatic, average-risk populations. 2 large retrospective studies included both symptomatic and asymptomatic persons. Risk for perforations from CT colonography seems higher in symptomatic persons.

Table 3 (continued)

Key Question and Test Validity Summary of Findings Comment
What are the test performance characteristics of CT colonography and fecal screening tests (e.g., high-sensitivity guaiac FOBT, FIT, or fecal DNA tests) for CRC screening as compared to an acceptable reference standard? (Key question 2b)
Fecal tests 11 total studies

FIT

Internal—Fair.
External—Fair. Most studies evaluated non-FDA-approved tests or those not on the U.S. market.
Studies (n = 86 498) provided estimates for Magstream (3 studies; n = 37 330 ), OC-Hemodia (3 studies; n = 35 351), FlexSure OBT (now Hemoccult ICT) (1 study; n = 5841), and Monohaem (2 studies; n = 7976). Across tests, sensitivity for CRC ranged from 61% to 91%; specificity ranged from 91% to 98%; rates of positive test results ranged from 2.0% to 5.9%. In a recent systematic review, sensitivity of nonrehydrated Hemoccult II for CRC ranged from 25% to 38% (except 1 outlier study with 60% sensitivity), and specificity was 98%-99%.

High-sensitivity guaiac

Internal—Fair.
External—Good.
In 1 study (n = 8104), Hemoccult SENSA (13.6% with positive test results) was more sensitive for CRC (79.4%) than Hemoccult II was (37.1%), but with lower specificity (86.7% vs. 97.7%). A second study (n = 5841) of left-sided CRC found that Hemoccult SENSA (10.1% with positive test results) had a sensitivity of 64.3% and specificity of 90.1%. Results from NCT00025025 ("Colorectal Cancer Screening: Fecal Blood vs. DNA." David Ahlquist, MD, Mayo Clinic Cancer Center, protocol chair), a randomized multicenter study of 2000 patients (age 50-80 y) undergoing FOBT, a newer-generation multitarget DNA-based panel testing of blood and of stool, and colonoscopy were recently published (Ahlquist DA, et al. Ann Intern Med. 2008;149:441-50) and answer some but not all questions.

Fecal DNA

Internal—Fair to poor. Test accuracy limited to selected subgroup (n = 2507) with CRC, advanced adenomas or tumors (n = 436), and a randomly selected group with minor (n = 648) or no (n = 1423) detected polyps. External—Fair to poor. Population was older (75% >65 y) than usual CRC screening population; panel test evaluated has been replaced and now requires premarket review by FDA. For PreGenPlus fecal DNA panel, sensitivity for CRC was 51.6%; specificity was 94.4%; rate of positive test results was 8.2%. In comparison, sensitivity of Hemoccult II for CRC was 12.9%; specificity was 94.3%; and rate of positive test results was 5.8%. Among all participants (n = 5486), more (11.7%) did not adhere to fecal DNA tests than to Hemoccult II (7.8%).  

CT colonography

Internal—Fair to good. One study used segmental unblinding to separate false-positive CT colonography findings from false-negative colonoscopy findings, and the other used second-look colonoscopy for discrepant large-lesion findings. External—Fair to poor. Best data from studies using CT technologies and experienced readers with uncertain generalizability to community CT colonography practices; uncertainty around reader variability. Among 1233 average-risk patients, per-patient sensitivity of 3D CT colonography was 93.8% for large (≥10 mm) adenomas and 88.7% for adenomas ≥6 mm; sensitivity estimates were not significantly different based on polyp size and were not significantly different from sensitivity estimates for colonoscopy. CIs are very wide. Specificity was significantly lower for lesions ≥6 mm (79.6%) than for lesions ≥8 mm (92.2%) or ≥10 mm (96%). Among 2531 average-risk patients, per-patient sensitivity of 3D or 2D CT colonography was 90% for large (≥10 mm) adenomas and 78% for adenomas ≥6 mm; sensitivity estimates were not significantly different based on polyp size, with very wide CIs. Specificity was 86% for lesions ≥10 mm and 88% for lesions ≥6 mm. Data could not be pooled for sensitivity and specificity estimates from the 2 largest studies because of statistically significant heterogeneity, except for sensitivity for adenomas ≥10 mm; pooled sensitivity was 92% (95% CI, 87%-96%; Q = 0.652; P = 0.42). In 2 other studies (n = 548), ranges of test performance for different readers for 3D CT colonography reported as follows: lesions ≥10 mm—sensitivity, 73%-100%, specificity, 98%-100%; lesions ≥6 mm—sensitivity, 60%-75%, specificity, 89%-99%. Sensitivity and specificity estimates for 3D imaging did not clearly differ from estimates for 2D imaging. Estimates for the proportion who would be referred for colonoscopy after CT colonography vary from 1 in 3 to 1 in 13, depending on referral size. Uncertainties remain about the performance of CT colonography screening in community settings. Available data support the need for quality standards for CT colonography screening.
What are the adverse effects of CT colonography and/or fecal screening tests (high-sensitivity FOBTs, FIT, and fecal DNA)? (Key question 3b)
Fecal tests - - No studies identified
CT colonography Internal—Fair.
External—Fair. Evidence for harms from CT colonography among asymptomatic persons not in community settings.
In 3 prospective studies (n = 4707) and the asymptomatic subgroup of 1 large retrospective study (n = 11 707), there were no serious complications, including perforation. In 1 study (n = 2531), 1 person was hospitalized for bacteremia after undergoing same-day CT colonography and colonoscopy. In the other large retrospective study (n = 11 870), which included both symptomatic and asymptomatic patients, 7 perforations occurred. However, only 1 perforation occurred in the asymptomatic population (the number of screening CT colonography procedures was not reported). Uncertainties remain about the implications of extracolonic findings, which require additional diagnostic tests or surgery in 7%-16% of cases. Uncertainties remain about about radiation-related risks. Indirect evidence estimates excess lifetime risk for cancer from low-dose (10 mSV) ionizing radiation to be 1 of 1000.

Table 3 (continued)

Key Question and Test Number of Studies and Study Design Limitations Consistency
What are the sensitivity and specificity of colonoscopy and flexible sigmoidoscopy when used to screen for CRC in the community practice setting? (Key question 2a)
Colonoscopy 3 cohort studies of accuracy of colonoscopy compared with CT colonography; "enhanced" reference standard of second-look colonoscopy for discrepancies between CT colonography and colonoscopy Small number (n = 1781) of patients studied with very few lesions. Number of colonoscopists varied from 5 to 50 per study, which complicates estimates of test accuracy with considerations of training and experience. Estimates of colonoscopy test performance are hampered by lack of a true gold standard. Variability in CT technology (e.g., use of contrast agent vs. no contrast agent, 2D vs. 3D). All studies conducted in average-risk screening populations.
Flexible sigmoidoscopy 6 cohort studies of screening colonoscopies Using screening colonoscopy to estimate flexible sigmoidoscopy results probably overestimates sensitivity because studies considered all neoplasia distal to the splenic flexure as detected by flexible sigmoidoscopy and the colonoscopy bowel preparation is superior to that for flexible sigmoidoscopy. Examiner skill may also vary from flexible sigmoidoscopy. Small number of CRC cases (20 total) limits precision of accuracy estimates. 6 screening colonoscopy studies (n = 14 938) simulate the flexible sigmoidoscopy screening with biopsy and colonoscopy referral for adenomas of any size; 2 of these screening colonoscopy studies (n = 6146) also simulate the flexible sigmoidoscopy screening without biopsy and colonoscopy referral for any lesion.
What are age-specific rates of harm from colonoscopy and flexible sigmoidoscopy in the community practice setting? (Key question 3a)
Colonoscopy 3 retrospective cohort studies, 14 prospective cohort studies Not all studies were conducted in a community setting. Duration of follow-up and methods for determining adverse events varied. Available data precluded determination of harms for colonoscopies with and without associated polypectomies. Age-specific harm rates could not be determined. No significant statistical heterogeneity in pooling estimates of serious adverse events. In meta-regression, only study setting by country was significantly associated with complications, but stratified analyses by country did not produce clinically significantly different harms estimates.
Flexible sigmoidoscopy 2 retrospective cohort studies, 6 prospective cohort studies 5 studies were not conducted in the United States, and 3 of 5 studies did not report endoscopist characteristics. Duration of follow-up and methods for determining adverse events varied. Age-specific harm rates could not be determined. No significant statistical heterogeneity in pooling estimates of serious adverse events. In meta-regression, only study setting by country was significantly associated with complications, but stratified analyses by country did not produce clinically significantly different harms estimates.

Table 3 (continued)

  Validity Summary of Findings Comment
What are the sensitivity and specificity of colonoscopy and flexible sigmoidoscopy when used to screen for CRC in the community practice setting? (Key question 2a)
Colonoscopy Internal—Fair.
External—Fair to poor. Estimates are not precise and are not clearly applicable to the community endoscopists.
Sensitivity of colonoscopy for CRC varied widely (20%-50%), largely because of small numbers of tumors (7 total CRC cases detected in all 3 studies). Sensitivity for large adenomas (≥10 mm) ranged from 77% to 100%. Sensitivity for smaller polyps is harder to estimate because of inconsistent reporting but suggests about a 10% miss rate. These data reinforce the need for performance standards for community colonoscopy, particularly for screening.
Flexible sigmoidoscopy Internal—Fair.
External—Fair. Estimates taken from studies conducted in average-risk screening populations but simulated from cohorts undergoing screening colonoscopy.
In 3982 average-risk adults, the sensitivity of simulated flexible sigmoidoscopy with biopsy for CRC throughout the colon ranged from 58.3% to 62.5%. Among 14,938 predominantly average-risk adults age 40-79 years, estimated sensitivity of flexible sigmoidoscopy with biopsy for advanced neoplasia throughout the colon generally ranged from 70% to 86%. The sensitivity of simulated flexible sigmoidoscopy without biopsy for CRC was 75%, based on a single study (n = 1994), and ranged from 77% to 86% for advanced neoplasia (n = 6146). Simulated estimates of test performance of flexible sigmoidoscopy with and without biopsy should be unnecessary once results are reported from 4 pending RCTs.
What are age-specific rates of harm from colonoscopy and flexible sigmoidoscopy in the community practice setting? (Key question 3a)
Colonoscopy Internal—Fair.
External—Good. All studies conducted either among asymptomatic persons or in a community setting, or both.
In 12 studies (n = 57,742), serious complications occurred in 2.8 per 1000 procedures (CI, 1.5-5.2 procedures). Limiting to 7 U.S. studies, serious complications were nonsignificantly reduced to 2.5 per 1000 procedures (CI, 1.0-6.1 procedures). -
Flexible sigmoidoscopy Internal—Fair.
External—Good. All studies conducted among asymptomatic, average-risk persons.
In 6 studies (n = 126 985), serious complications occurred in 0.34 per 1000 procedures (CI, 0.06-1.9 procedures). -

2D = 2-dimensional; 3D = 3-dimensional; CRC = colorectal cancer; CT = computed tomography; FDA = Food and Drug Administration; FIT = fecal immunochemical test; FOBT = fecal occult blood test; RCT = randomized, controlled trial.
* Results reported in this table are limited to those reported in the article, which is derived from a larger, more detailed report available at Return to Table of Contents

Archived: Appendix Table 1. Eligibility Criteria for Studies, by Key Question

Appendix Table 1. Eligibility Criteria for Studies, by Key Question

Key Question Population Study Design Setting Outcomes Other
KQ1: Impact of screening on mortality (for any screening test) Age ≥40 y, average risk; recruited from primary care or primary care-comparable population Systematic evidence review; RCT; cluster RCT; or well-designed CCT, cohort, and case—control studies Primary care or other setting with primary care—comparable population Mortality (all-cause or CRC-specific) For guaiac FOBT, only updates for the trials included in the previous review were considered
KQ2a: Accuracy of flexible sigmoidoscopy and colonoscopy (community setting) Age ≥40 y, average risk; recruited from primary care or primary care—comparable population Systematic evidence review; RCT; cohort studies; systematically selected case series; screening registry Community primary care or other setting with primary care—comparable population Sensitivity and specificity (per person) or miss rates (per polyp); yield for CRC, advanced neoplasia, or adenomas by size Colonoscopy as reference standard; full spectrum of disease represented; indeterminate results not excluded
KQ2b: Accuracy of newer screening tests (CT colonography, high-sensitivity FOBT, FIT, fecal DNA) Age ≥40 y, average risk; recruited from primary care or primary care—comparable population Systematic evidence review; RCT; diagnostic cohort studies; systematically selected case series; screening registry Any Sensitivity and specificity (per person) or miss rates (per polyp); yield for CRC, advanced neoplasia, or adenomas by size Colonoscopy (or registry follow-up) as reference standard; full spectrum of disease represented; indeterminate results not excluded
KQ3a: Harms of flexible sigmoidoscopy and colonoscopy (community setting) Age ≥40 y, average risk; recruited from primary care or primary care—comparable population Systematic evidence review; RCT/CCT; registries; large-database observational studies, cohort studies; cross-sectional studies; systematically selected case series Community primary care or other setting with primary care—comparable population Adverse events requiring hospitalization, including perforation, major bleeding, severe abdominal symptoms, cardiovascular events, and/or resulting in death Harms due to bowel preparation and sedation considered separate from serious adverse events
KQ3b: Harms of newer screening tests (CT colonography, high-sensitivity FOBT, FIT, fecal DNA) Age ≥40 y, average risk Systematic evidence review; RCT/CCT; registries; large-database observational studies, cohort studies; cross-sectional studies; systematically selected case series Any Adverse events requiring hospitalization, including perforation, major bleeding, severe abdominal symptoms, cardiovascular events, and/or resulting in death Potential harms due to radiation and extracolonic findings considered separate from serious adverse events

CCT = controlled clinical trial; CRC = colorectal cancer; CT = computed tomography; FIT . fecal immunochemical test; FOBT = fecal occult blood test; KQ = key question; RCT = randomized, controlled trial.

Archived: Appendix Table 2. U.S. Preventive Services Task Force Design-Specific Quality Rating Criteria

Systematic reviews
Criteria
   Comprehensiveness of sources considered/search strategy used.
   Standard appraisal of included studies.
   Validity of conclusions.
   Recency and relevance are especially important for systematic reviews.

RCTs and cohort studies
Criteria
   Initial assembly of comparable groups.
     For RCTs: adequate randomization, including first concealment and whether potential confounders were distributed equally among groups.
     For cohort studies: consideration of potential confounders with either restriction or measurement for adjustment in the analysis; consideration of inception cohorts.
   Maintenance of comparable groups (includes attrition, crossovers, adherence, contamination)
   Important differential loss to follow-up or overall high loss to follow-up.
   Measurements: equal, reliable, and valid (includes masking of outcome assessment)
   Clear definition of the interventions.
   All important outcomes considered.

Case—control studies
Criteria
   Accurate ascertainment of cases.
   Nonbiased selection of case-patients/controls with exclusion criteria applied equally to both.
   Response rate.
   Diagnostic testing procedures applied equally to each group.
   Measurement of exposure accurate and applied equally to each group.
   Appropriate attention to potential confounding variables.

Diagnostic accuracy studies
Criteria
   Screening test relevant, available for primary care, adequately described.
   Credible reference standard used, performed regardless of test results.
   Reference standard interpreted independently of screening test.
   Indeterminate result handled in a reasonable manner.
   Adequate spectrum of patients included in study.
   Adequate sample size.
   Administration of reliable screening test.

RCT = randomized, controlled trial.

Archived: Appendix Table 3. SAS Code for the Meta-Analysis of Serious Complications

The following SAS code shows how to calculate the combined rate of total serious complications and examines the impact of Community_setting (1 = Yes, 0 = No) on total serious complication rate using a logistic random-effects model with PROC NLMIXED.

Data totalSC; input Study $ n_proc n_serious_tot Community_setting
/* Community_setting = 1 if the study was conducted in a community setting; 0, otherwise */
Datalines
Kewenter_1996 190 3 0
Robinson_1999 1474 7 1
Thiis_1999 521 1 0
Nelson_2002 3196 18 0
Segnan_2002 775 2 0
Pickhardt_2003 1233 1 0
Cotterill_2005 324 0 1
Ko_2006 502 8 0
Levin_2006 16318 44 1
Rathgaber_2006 12407 14 1
Ko_2007 18271 45 1
Johnson_2008 2531 2 1

/** To obtain a combined rate of total serious complication rate */

proc nlmixed data = totalSC;
parms beta0 = -7.0 s2u = 0.5; /* Specify the initial value */
eta = beta0 + u;
/* Specify the model on logit scale where beta0 will be used to estimate combined complication rate, and u is the random-effects term across studies */

expeta = exp(eta);
p = expeta/(1+expeta);
model n_serious_tot ˜ binomial(n_proc,p);
/* Specify the distribution for the number of complications */

random u ˜ normal(0,s2u) subject=study; /* Specify the distribution of random effects */

estimate "Complication Rate" exp(beta0)/(1+exp(beta0));
/* Obtain the combined complication rate using beta0 */
run;

/** To examine the impact of community setting on the total serious complication rate */

proc nlmixed data = totalSC;
parms beta0 = -7.0 s2u = 0.5 beta1 = 0.5; /* Specify the initial values */
eta = beta0 + beta1 * Community_setting + u;
/* Impact of community setting is investigated by beta1*/

expeta = exp(eta);
p = expeta/(1+expeta);
model n_serious_tot ˜ binomial(n_proc,p);
/* Specify the distribution for the number of complications */

random u ˜ normal(0,s2u) subject=study;
/* Specify the distribution of random effects */
run

Archived: Appendix Table 4. Extracolonic Findings in Asymptomatic Persons Undergoing Computed Tomographic Colonography

Study, Year
(Reference)
Study Design Population, n Follow-Up Description of Extracolonic Findings (as Reported in Study) Work-up of Extracolonic Findings (with Final Disposition at End of Study)
"Average-risk" populations
Johnson et al., 200855 Prospective cohort study 2531, asymptomatic NR 66% persons with any extracolonic finding, 16% persons had extracolonic findings that were considered to require additional evaluation or urgent care Subsequent evaluation NR
Pickhardt et al., 200870 Prospective cohort study 2195, asymptomatic Chart review, up to 18 mo 9.3% (204 of 2195) at least "moderate" or "high" clinical significance 7.2% (157 of 2195) recommended to have additional diagnostic evaluation, 6.1% (133 of 2195) had additional diagnostic evaluation, 2.5% (55 of 2195) with confirmed diagnosis of an unsuspected condition of at least "moderate" importance, 1.0% (22 of 2195) required surgical procedures as follow-up
Kim et al., 200767 Prospective cohort study 3120, 98% asymptomatic NR 2.2% (70 of 3120) persons with potentially important finding (C-RADS E4), 8.5% (265 of 3120) persons with probably unimportant finding (C-RADS E3), 47.8% (1490 of 3120) persons with clinically unimportant finding (C-RADS E2) 7.7% (241 of 3120) recommended to have additional diagnostic evaluation, 0.3% (8 of 3120) persons with extracolonic cancer (treatment NR)
Pickhardt et al., 200766 Prospective cohort study 2014, presumed asymptomatic Chart review, unclear duration Only evaluated extracolonic GI tumors, 0.5% (10 of 2014) persons with focal extracolonic GI tumors 0.5% (10 of 2014) had further diagnostic evaluation, 0.3% (7 of 2014) required surgical resection, 0.05% (1 of 2014) required endoscopic resection; all GI tumors found to be benign
Chin et al., 200568 Prospective cohort study 432, asymptomatic Through general practitioner, 2 y 27.3% (118 of 432) persons with any extracolonic findings, 7.4% (32 of 432) persons with clinically relevant extracolonic findings 7.4% (32 of 432) required further diagnostic evaluation: 1.8% (8 of 432) cancer or aneurysms, 5.5% (24 of 432) benign lesions; 1.4% (6 of 432) ongoing follow-up at 2 y, none required treatment at 2 y
Gluecker et al., 200369 Prospective cohort study 681, asymptomatic Chart review, at least 12 mo 69% (469 of 681) persons with any extracolonic finding, 10% (71 of 681) persons with findings of "high" clinical importance, 27% (183 of 681) persons with findings of "moderate" clinical importance Total 94 follow-up diagnostic procedures, 15 follow-up diagnostic procedures in 183 persons with "moderate" findings, 1% (9 of 681) needed treatment
Pickhardt et al., 200349 Prospective cohort study 1245, asymptomatic NR 4.5% (56 of 1245) persons with findings of "high" clinical importance, >13% (169 of 1245) persons with findings of "moderate" clinical importance 0.4% (5 of 1245) extracolonic cancer (treatment NR)
Asymptomatic surveillance populations
Ginnerup Pedersen et al., 200364 Prospective cohort study 75, asymptomatic, undergoing surveillance Chart review, 6 mo 65% (49 of 75) persons with any extracolonic finding, 12% (9 of 75) persons with extracolonic findings warranting additional work-up 11% (8 of 75) had further diagnostic evaluation, 3% (2 of 75) had surgery because of findings or complications of work-up
Hara et al., 200065 Prospective cohort study 264, asymptomatic but 162 undergoing surveillance Chart review, 7-22 mo 41% (109 of 264) with any extracolonic findings, 11% (30 of 264) persons with extracolonic findings of "high" clinical importance, 17% (46 of 264) persons with extracolonic findings of "moderate" clinical importance 6.8% (18 of 264) had further diagnostic evaluation, 1.9% (5 of 264) had surgery because of malignant or nonmalignant findings, 1.5% (4 of 264) required ongoing follow-up

C-RADS = Colonography Reporting and Data System; GI = gastrointestinal; NR = not reported.

Archived: Appendix Figure 1. Proportion of total serious complications in colonoscopy studies

Select Text Description below for details

Text Description.

Appendix Figure 1. Proportion of total serious complications in colonoscopy studies (Text Description)

Study, Year
(Reference)
Cases, n Total Procedures, n Proportion (95% CI)*
Kewenter and Brevinge, 199674 3 190 0.00142 (0.000294-0.00415)
Robinson et al., 199983 7 1474 0.00475 (0.00191-0.00976)
Thiis-Evensen et al., 199985 1 521 0.00192 (0.0000486-0.0106)
Nelson et al., 200280 18 3196 0.00563 (0.00334-0.00889)
Segnan et al., 200284 2 775 0.00258 (0.000313-0.00929)
Pickhardt et al., 200349 1 1233 0.00081 (0.000021-0.00451)
Cotterill et al., 200573 0 324 0 (0-0.0113)
Ko et al., 200776 8 502 0.0159 (0.00690-0.0312)
Levin et al., 200679 44 16,318 0.00270 (0.00196-0.00362)
Rathgaber and Wick, 200682 14 12,407 0.00113 (0.000617-0.00189)
Ko et al., 200775 45 18,271 0.00246 (0.00180-0.00329)
Johnson et al., 200855 2 2351 0.00079 (0.000096-0.00285)
Combined (excluding Ko et al., 200775)     0.00278 (0.00135-0.00571)
All studies combined     0.00277 (0.00148-0.00516)

 

Test for heterogeneity for all studies based on logit of proportions using a random-effects model (P = 0.13).
* 95% CIs are exact confidence intervals.

Archived: Appendix Figure 2. Proportion of total serious complications in flexible sigmoidoscopy studies

Select Text Description below for details

 

Text Description.

Appendix Figure 2. Proportion of total serious complications in flexible sigmoidoscopy studies (Text Description)

Study, Year
(Reference)
Cases, n Total Procedures, n Proportion (95% CI)*
Kewenter and Brevinge, 199674 3 2108 0.00142 (0.000294-0.00415)
Atkin et al., 199872 3 1285 0.00233 (0.000482-0.00681)
Thiis-Evensen et al., 199985 1 446 0.00224 (0.0000568-0.0124)
Wallace et al., 199997 0 3701 0 (0-0.000996)
Levin et al., 200296 7 109,534 0.0000639 (0.0000257-0.000132)
Segnan et al., 200284 2 9911 0.000202 (0.0000244-0.000729)
All studies combined     0.000341 (0.0000607-0.00192)

 

Test for heterogeneity for all studies based on logit of proportions using a random-effects model (P = 0.26).
* 95% CIs are exact confidence intervals.

References:
  1. American Cancer Society. Colorectal Cancer Facts and Figures Special Edition. Atlanta: American Cancer Society; 2008.
  2. Jackson-Thompson J, Ahmed F, German RR, Lai SM, Friedman C. Descriptive epidemiology of colorectal cancer in the United States, 1998-2001. Cancer 2006;107:1103-11. [PMID: 16835911]
  3. Chu KC, Tarone RE, Chow WH, Alexander GA. Colorectal cancer trends by race and anatomic subsites, 1975 to 1991. Arch Fam Med 1995;4:849-56. [PMID: 7551132]
  4. Cooper GS, Yuan Z, Rimm AA. Racial disparity in the incidence and case-fatality of colorectal cancer: analysis of 329 United States counties. Cancer Epidemiol Biomarkers Prev 1997;6:283-5. [PMID: 9107433]
  5. Cress RD, Morris CR, Wolfe BM. Cancer of the colon and rectum in California: trends in incidence by race/ethnicity, stage, and subsite. Prev Med 2000;31:447-53. [PMID: 11006071]
  6. Troisi RJ, Freedman AN, Devesa SS. Incidence of colorectal carcinoma in the U.S.: an update of trends by gender, race, age, subsite, and stage, 1975-1994. Cancer 1999;85:1670-6. [PMID: 10223559]
  7. Ward E, Jemal A, Cokkinides V, Singh GK, Cardinez C, Ghafoor A, et al. Cancer disparities by race/ethnicity and socioeconomic status. CA Cancer J Clin 2004;54:78-93. [PMID: 15061598]
  8. Surveillance, Epidemiology, and End Results Program. Contents of the SEER Cancer Statistics Review, 1975-2003. Accessed at http://seer.cancer.gov/csr/1975_2003/ on 16 October 2006.
  9. U.S. Preventive Services Task Force. Clinical Guide to Preventive Services, 2nd ed. Rockville, MD: Agency for Healthcare Research and Quality; 1996.
  10. Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007:CD001216. [PMID: 17253456]
  11. Pignone M, Rich M, Teutsch SM, Berg AO, Lohr KN. Screening for colorectal cancer in adults at average risk: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:132-41. [PMID: 12118972]
  12. U.S. Preventive Services Task Force. Screening for colorectal cancer. In: Pocket Guide to Clinical Preventive Services, 2007: Recommendations of the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2007:32-5.
  13. Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:96-104. [PMID: 12118964]
  14. U.S. Preventive Services Task Force. Screening for colorectal cancer: recommendation and rationale. Ann Intern Med 2002;137:129-31. [PMID: 12118971]
  15. Klabunde CN, Frame PS, Meadow A, Jones E, Nadel M, Vernon SW. A national survey of primary care physicians' colorectal cancer screening recommendations and practices. Prev Med 2003;36:352-62. [PMID: 12634026]
  16. Meissner HI, Breen N, Klabunde CN, Vernon SW. Patterns of colorectal cancer screening uptake among men and women in the United States. Cancer Epidemiol Biomarkers Prev 2006;15:389-94. [PMID: 16492934]
  17. Breen N, Wagener DK, Brown ML, Davis WW, Ballard-Barbash R. Progress in cancer screening over a decade: results of cancer screening from the 1987, 1992, and 1998 National Health Interview Surveys. J Natl Cancer Inst 2001;93:1704-13. [PMID: 11717331]
  18. Yeazel MW, Church TR, Jones RM, Kochevar LK, Watt GD, Cordes JE, et al. Colorectal cancer screening adherence in a general population. Cancer Epidemiol Biomarkers Prev 2004;13:654-7. [PMID: 15066933]
  19. Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin 2007;57:90-104. [PMID: 17392386]
  20. Centers for Disease Control and Prevention (CDC). Use of colorectal cancer tests—United States, 2002, 2004, and 2006. MMWR Morb Mortal Wkly Rep 2008;57:253-8. [PMID: 18340331]
  21. Ananthakrishnan AN, Schellhase KG, Sparapani RA, Laud PW, Neuner JM. Disparities in colon cancer screening in the Medicare population. Arch Intern Med 2007;167:258-64. [PMID: 17296881]
  22. Pollack LA, Blackman DK, Wilson KM, Seeff LC, Nadel MR. Colorectal cancer test use among Hispanic and non-Hispanic U.S. populations. Preventing Chronic Disease [serial online]. 2006;3. Accessed at http://www.cdc.gov/pcd/issues/2006/apr/05_0120.htm on 22 September 2008.
  23. Schootman M, Jeffe DB, Baker EA, Walker MS. Effect of area poverty rate on cancer screening across US communities. J Epidemiol Community Health 2006;60:202-7. [PMID: 16476748]
  24. Zauber AG, Lansdorp-Vogelaar I, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM. Evaluating test strategies for colorectal cancer screening: a decision analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2008;149:659-69.
  25. Whitlock EP, Lin J, Liles E, Beil TL, Fu R, O'Connor E, et al. Screening for colorectal cancer: an updated systematic review. Rockville, MD: Agency for Healthcare Research and Quality; 2008.
  26. Whitlock EP, Lin JS, Chou R, Shekelle P, Robinson KA. Using existing systematic reviews in complex systematic reviews. Ann Intern Med 2008;148:776-82. [PMID: 18490690]
  27. Mulhall BP, Veerappan GR, Jackson JL. Meta-analysis: computed tomographic colonography. Ann Intern Med 2005;142:635-50. [PMID: 15838071]
  28. HAYES. Computed tomography colonography (virtual colonoscopy). Lansdale, PA: HAYES; 2006.
  29. Blue Cross Blue Shield Association. Fecal DNA analysis for colorectal cancer screening. Accessed at http://www.bcbs.com/blueresources/tec/vols/21/21_06.html on August 17, 2006.
  30. Lijmer JG, Mol BW, Heisterkamp S, Bonsel GJ, Prins MH, van der Meulen JH, et al. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 1999;282:1061-6. [PMID: 10493205]
  31. Soares-Weiser K, Burch J, Duffy S, St John J, Smith S, Westwood M, et al. Diagnostic accuracy and cost-effectiveness of faecal occult blood tests used in screening for colorectal cancer: a systematic review. York, United Kingdom: Centre for Reviews and Dissemination, University of York; 2007.
  32. Whiting P, Rutjes AW, Reitsma JB, Glas AS, Bossuyt PM, Kleijnen J. Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med 2004;140:189-202. [PMID: 14757617]
  33. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al.Methods Work Group, Third US Preventive Services Task Force. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20:21-35. [PMID: 11306229]
  34. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539-58. [PMID: 12111919]
  35. Turner RM, Omar RZ, Yang M, Goldstein H, Thompson SG. A multilevel model framework for meta-analysis of clinical trials with binary outcomes. Stat Med 2000;19:3417-32. [PMID: 11122505]
  36. Hamza TH, van Houwelingen HC, Stijnen T. The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 2008;61:41-51. [PMID: 18083461]
  37. Blue Cross Blue Shield Association. Immunochemical versus guaiac fecal occult blood tests. Accessed at http://www.bcbs.com/tec/vol19/19_05.html on 17 August 2006.
  38. Allison JE, Sakoda LC, Levin TR, Tucker JP, Tekawa IS, Cuff T, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007;99:1462-70. [PMID: 17895475]
  39. Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med 1996;334:155-9. [PMID: 8531970].
  40. Cheng TI, Wong JM, Hong CF, Cheng SH, Cheng TJ, Shieh MJ, et al. Colorectal cancer screening in asymptomaic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests. J Formos Med Assoc 2002;101:685-90. [PMID: 12517041]
  41. Itoh M, Takahashi K, Nishida H, Sakagami K, Okubo T. Estimation of the optimal cut off point in a new immunological faecal occult blood test in a corporate colorectal cancer screening programme. J Med Screen 1996;3:66-71. [PMID: 8849762]
  42. Launoy GD, Bertrand HJ, Berchi C, Talbourdet VY, Guizard AV, Bouvier VM, et al. Evaluation of an immunochemical fecal occult blood test with automated reading in screening for colorectal cancer in a general average-risk population. Int J Cancer 2005;115:493-6. [PMID: 15700317]
  43. Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, et al. A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007;146:244-55. [PMID: 17310048]
  44. Morikawa T, Kato J, Yamaji Y, Wada R, Mitsushima T, Shiratori Y. A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population. Gastroenterology 2005;129:422-8. [PMID: 16083699]
  45. Nakama H, Yamamoto M, Kamijo N, Li T, Wei N, Fattah AS, et al. Colonoscopic evaluation of immunochemical fecal occult blood test for detection of colorectal neoplasia. Hepatogastroenterology 1999;46:228-31. [PMID: 10228797]
  46. Nakama H, Kamijo N, Abdul Fattah AS, Zhang B. Validity of immunological faecal occult blood screening for colorectal cancer: a follow up study. J Med Screen 1996;3:63-5. [PMID: 8849761]
  47. Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME.Colorectal Cancer Study Group. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704-14. [PMID: 15616205]
  48. Haug U, Hillebrand T, Bendzko P, Löw M, Rothenbacher D, Stegmaier C, et al. Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults. Clin Chem 2007;53:787-90. [PMID: 17317884]
  49. Pickhardt PJ, Choi JR, Hwang I, Butler JA, Puckett ML, Hildebrandt HA, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349:2191-200. [PMID: 14657426]
  50. Macari M, Milano A, Lavelle M, Berman P, Megibow AJ. Comparison of time-efficient CT colonography with two- and three-dimensional colonic evaluation for detecting colorectal polyps. AJR Am J Roentgenol 2000;174:1543-9. [PMID: 10845478]
  51. Macari M, Bini EJ, Jacobs SL, Naik S, Lui YW, Milano A, et al. Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology 2004;230:629-36. [PMID: 14739311]
  52. Rex DK, Vining D, Kopecky KK. An initial experience with screening for colon polyps using spiral CT with and without CT colography (virtual colonoscopy). Gastrointest Endosc 1999;50:309-13. [PMID: 10462648]
  53. Johnson CD, Fletcher JG, MacCarty RL, Mandrekar JN, Harmsen WS, Limburg PJ, et al. Effect of slice thickness and primary 2D versus 3D virtual dissection on colorectal lesion detection at CT colonography in 452 asymptomatic adults. AJR Am J Roentgenol 2007;189:672-80. [PMID: 17715116]
  54. Kim SH, Lee JM, Eun HW, Lee MW, Han JK, Lee JY, et al. Two- versus three-dimensional colon evaluation with recently developed virtual dissection software for CT colonography. Radiology 2007;244:852-64. [PMID: 17709833]
  55. Johnson CD, Chen MH, Toledano AY, Heiken JP, Dachman A, Kuo MD, et al. Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med 2008;359:1207-17. [PMID: 18799557]
  56. Pickhardt PJ, Nugent PA, Choi JR, Schindler WR. Flat colorectal lesions in asymptomatic adults: implications for screening with CT virtual colonoscopy. AJR Am J Roentgenol 2004;183:1343-7. [PMID: 15505301]
  57. Pickhardt PJ. Incidence of colonic perforation at CT colonography: review of existing data and implications for screening of asymptomatic adults. Radiology 2006;239:313-6. [PMID: 16641348]
  58. Edwards JT, Mendelson RM, Fritschi L, Foster NM, Wood C, Murray D, et al. Colorectal neoplasia screening with CT colonography in average-risk asymptomatic subjects: community-based study. Radiology 2004;230:459-64. [PMID: 14688402]
  59. Sosna J, Blachar A, Amitai M, Barmeir E, Peled N, Goldberg SN, et al. Colonic perforation at CT colonography: assessment of risk in a multicenter large cohort. Radiology 2006;239:457-63. [PMID: 16543590]
  60. Jensch S, van Gelder RE, Venema HW, Reitsma JB, Bossuyt PM, Laméris JS, et al. Effective radiation doses in CT colonography: results of an inventory among research institutions. Eur Radiol 2006;16:981-7. [PMID: 16418863]
  61. van Gelder RE, Venema HW, Serlie IW, Nio CY, Determann RM, Tipker CA, et al. CT colonography at different radiation dose levels: feasibility of dose reduction. Radiology 2002;224:25-33. [PMID: 12091658]
  62. Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, Board on Radiation Effects, Research Division on Earth and Life Sciences, National Research Council of the National Academics. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII, Phase 2. Washington, DC: National Academies Press; 2006.
  63. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA 2007;298:317-23. [PMID: 17635892]
  64. Ginnerup Pedersen B, Rosenkilde M, Christiansen TE, Laurberg S. Extracolonic findings at computed tomography colonography are a challenge. Gut 2003;52:1744-7. [PMID: 14633954]
  65. Hara AK, Johnson CD, MacCarty RL, Welch TJ. Incidental extracolonic findings at CT colonography. Radiology 2000;215:353-7. [PMID: 10796907]
  66. Pickhardt PJ, Kim DH, Taylor AJ, Gopal DV, Weber SM, Heise CP. Extracolonic tumors of the gastrointestinal tract detected incidentally at screening CT colonography. Dis Colon Rectum 2007;50:56-63. [PMID: 17115333]
  67. Kim DH, Pickhardt PJ, Taylor AJ, Leung WK, Winter TC, Hinshaw JL, et al. CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med 2007;357:1403-12. [PMID: 17914041]
  68. Chin M, Mendelson R, Edwards J, Foster N, Forbes G. Computed tomographic colonography: prevalence, nature, and clinical significance of extracolonic findings in a community screening program. Am J Gastroenterol 2005;100:2771-6. [PMID: 16393234]
  69. Gluecker TM, Johnson CD, Wilson LA, Maccarty RL, Welch TJ, Vanness DJ, et al. Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology 2003;124:911-6. [PMID: 12671887]
  70. Pickhardt PJ, Hanson ME, Vanness DJ, Lo JY, Kim DH, Taylor AJ et al. Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology 2008;249:151-59.
  71. Zalis ME, Barish MA, Choi JR, Dachman AH, Fenlon HM, Ferrucci JT, et al.Working Group on Virtual Colonoscopy. CT colonography reporting and data system: a consensus proposal [Editorial]. Radiology 2005;236:3-9. [PMID: 15987959]
  72. Atkin WS, Hart A, Edwards R, McIntyre P, Aubrey R, Wardle J, et al. Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening. Gut 1998;42:560-5. [PMID: 9616321]
  73. Cotterill M, Gasparelli R, Kirby E. Colorectal cancer detection in a rural community. Development of a colonoscopy screening program. Can Fam Physician 2005;51:1224-8. [PMID: 16190175]
  74. Kewenter J, Brevinge H. Endoscopic and surgical complications of work-up in screening for colorectal cancer. Dis Colon Rectum 1996;39:676-80. [PMID: 8646956]
  75. Ko CW, Riffle S, Morris CG, Michaels L, Holub JL, Shapiro J, et al. Complications after screening and surveillance colonoscopy [Abstract]. Gastroenterology 2007;132:A149.
  76. Ko CW, Riffle S, Shapiro JA, Saunders MD, Lee SD, Tung BY, et al. Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy. Gastrointest Endosc 2007;65:648-56. [PMID: 17173914]
  77. Korman LY, Overholt BF, Box T, Winker CK. Perforation during colonoscopy in endoscopic ambulatory surgical centers. Gastrointest Endosc 2003;58:554-7. [PMID: 14520289]
  78. Lee YC, Wang HP, Chiu HM, Lin CP, Huang SP, Lai YP, et al. Factors determining post-colonoscopy abdominal pain: prospective study of screening colonoscopy in 1000 subjects. J Gastroenterol Hepatol 2006;21:1575-80. [PMID: 16928219]
  79. Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, et al. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med 2006;145:880-6. [PMID: 17179057]
  80. Nelson DB, McQuaid KR, Bond JH, Lieberman DA, Weiss DG, Johnston TK. Procedural success and complications of large-scale screening colonoscopy. Gastrointest Endosc 2002;55:307-14. [PMID: 11868001]
  81. Newcomer MK, Shaw MJ, Williams DM, Jowell PS. Unplanned work absence following outpatient colonoscopy. J Clin Gastroenterol 1999;29:76-8. [PMID: 10405238]
  82. Rathgaber SW, Wick TM. Colonoscopy completion and complication rates in a community gastroenterology practice. Gastrointest Endosc 2006;64:556-62. [PMID: 16996349]
  83. Robinson MH, Hardcastle JD, Moss SM, Amar SS, Chamberlain JO, Armitage NC, et al. The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer. Gut 1999;45:588-92. [PMID: 10486370]
  84. Segnan N, Senore C, Andreoni B, Aste H, Bonelli L, Crosta C, et al.SCORE Working Group—Italy. Baseline findings of the Italian multicenter randomized controlled trial of "once-only sigmoidoscopy"—SCORE. J Natl Cancer Inst 2002;94:1763-72. [PMID: 12464648]
  85. Thiis-Evensen E, Hoff GS, Sauar J, Langmark F, Majak BM, Vatn MH. Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999;34:414-20. [PMID: 10365903]
  86. Betés Ibáñez M, Muñoz-Navas MA, Duque JM, Angós R, Macías E, Súbtil JC, et al. Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy. Gastrointest Endosc 2004;59:634-41. [PMID: 15114305]
  87. Ikeda Y, Mori M, Miyazaki M, Yoshizumi T, Maehara Y, Sugimachi K. Significance of small distal adenoma for detection of proximal neoplasms in the colorectum. Gastrointest Endosc 2000;52:358-61. [PMID: 10968850]
  88. Schoenfeld P, Cash B, Flood A, Dobhan R, Eastone J, Coyle W, et al.CONCeRN Study Investigators. Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med 2005;352:2061-8. [PMID: 15901859].
  89. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000;343:162-8. [PMID: 10900274]
  90. Imperiale TF, Wagner DR, Lin CY, Larkin GN, Rogge JD, Ransohoff DF. Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening for colorectal cancer. Ann Intern Med 2003;139:959-65. [PMID: 14678915]
  91. Anderson JC, Alpern Z, Messina CR, Lane B, Hubbard P, Grimson R, et al. Predictors of proximal neoplasia in patients without distal adenomatous pathology. Am J Gastroenterol 2004;99:472-7. [PMID: 15056088]
  92. Schoenfeld P, Lipscomb S, Crook J, Dominguez J, Butler J, Holmes L, et al. Accuracy of polyp detection by gastroenterologists and nurse endoscopists during flexible sigmoidoscopy: a randomized trial. Gastroenterology 1999;117:312-8. [PMID: 10419911]
  93. Schoen RE, Pinsky PF, Weissfeld JL, Bresalier RS, Church T, Prorok P, et al.Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Group. Results of repeat sigmoidoscopy 3 years after a negative examination. JAMA 2003;290:41-8. [PMID: 12837710]
  94. Burke CA, Elder K, Lopez R. Screening for colorectal cancer with flexible sigmoidoscopy: is a 5-yr interval appropriate? A comparison of the detection of neoplasia 3 yr versus 5 yr after a normal examination. Am J Gastroenterol 2006;101:1329-32. [PMID: 16771957]
  95. Jain A, Falzarano J, Jain A, Decker R, Okubo G, Fujiwara D. Outcome of 5,000 flexible sigmoidoscopies done by nurse endoscopists for colorectal screening in asymptomatic patients. Hawaii Med J 2002;61:118-20. [PMID: 12148407]
  96. Levin TR, Conell C, Shapiro JA, Chazan SG, Nadel MR, Selby JV. Complications of screening flexible sigmoidoscopy. Gastroenterology 2002;123:1786-92. [PMID: 12454834]
  97. Wallace MB, Kemp JA, Meyer F, Horton K, Reffel A, Christiansen CL, et al. Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists. Am J Med 1999;107:214-8. [PMID: 10492313]
  98. Viiala CH, Olynyk JK. Outcomes after 10 years of a community-based flexible sigmoidoscopy screening program for colorectal carcinoma. Med J Aust 2007;187:274-7. [PMID: 17767431]
  99. Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol 2003;38:635-42. [PMID: 12825872]
  100. UK Flexible Sigmoidoscopy Screening Trial Investigators. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002;359:1291-300. [PMID: 11965274]
  101. Weissfeld JL, Schoen RE, Pinsky PF, Bresalier RS, Church T, Yurgalevitch S, et al. PLCO Project Team. Flexible sigmoidoscopy in the PLCO cancer screening trial: results from the baseline screening examination of a randomized trial. J Natl Cancer Inst 2005;97:989-97. [PMID: 15998952]
  102. Bossuyt PM, Irwig L, Craig J, Glasziou P. Comparative accuracy: assessing new tests against existing diagnostic pathways. BMJ 2006;332:1089-92. [PMID: 16675820]
  103. Lord SJ, Irwig L, Simes RJ. When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials? Ann Intern Med 2006;144:850-5. [PMID: 16754927]
  104. Centers for Medicare & Medicaid Services. 2008 clinical diagnostic laboratory fee schedule. Accessed at http://www.cms.hhs.gov/apps/ama/license.asp?file=/ClinicalLabFeeSched/downloads/08clab-b.zip on 17 June 2008.
  105. Woolf SH. A smarter strategy? Reflections on fecal DNA screening for colorectal cancer [Editorial]. N Engl J Med 2004;351:2755-8. [PMID: 15616212]
  106. Decision Memo for Screening DNA Stool Test for Colorectal Cancer (CAG-00144N). Washington, DC: Centers for Medicare & Medicaid Services. Accessed at http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=212 on 28 April 2008.
  107. U.S. Food and Drug Administration, U.S. Department of Health and Human Services. Warning Letter. 2007. Accessed a http://www.fda.gov/foi/warning_letters/s6568c.htm on 17 October 2007.
  108. Guide to the clinical use of Pre-Gen Plus: Non-invasive colorectal cancer screening. Burlington, NC: Laboratory Corporation of America; 2003.
  109. Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al.American Cancer Society Colorectal Cancer Advisory Group. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008;58:130-60. [PMID: 18322143]
  110. Graser A. Results from the "Munich Colorectal Cancer Prevention Trial": comparison of low-dose 64 MDCT colonography and video colonoscopy in a screening population [Abstract]. Radiological Society of North America Meeting; 28 November 2006.
  111. Ransohoff DF. Virtual colonoscopy-what it can do vs what it will do. JAMA 2004;291:1772-74.
  112. Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation exposure. N Engl J Med 2007;357:2277-84. [PMID: 18046031]
  113. Brenner DJ, Georgsson MA. Mass screening with CT colonography: should the radiation exposure be of concern? Gastroenterology 2005;129:328-37. [PMID: 16012958]
  114. Liedenbaum MH, Venema HW, Stoker J. Radiation dose in CT colonography-trends in time and differences between daily practice and screening protocols. Eur Radiol 2008;18:2222-2230. [PMID: 18491095]
  115. Hassan C, Pickhardt PJ, Pickhardt P, Laghi A, Kim DH, Kim D, et al. Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis. Arch Intern Med 2008;168:696-705. [PMID: 18413551]
  116. Fletcher RH, Pignone M. Extracolonic findings with computed tomographic colonography: asset or liability? [Editorial] Arch Intern Med 2008;168:685-6. [PMID: 18413549]
  117. Kim DH, Pickhardt PJ, Hoff G, Kay CL. Computed tomographic colonography for colorectal screening. Endoscopy 2007;39:545-9. [PMID: 17554653]
  118. Burling D, Halligan S, Altman DG, Atkin W, Bartram C, Fenlon H, et al. Polyp measurement and size categorisation by CT colonography: effect of observer experience in a multi-centre setting. Eur Radiol 2006;16:1737-44. [PMID: 16636803]
  119. Young BM, Fletcher JG, Paulsen SR, Booya F, Johnson CD, Johnson KT, et al. Polyp measurement with CT colonography: multiple-reader, multiple-workstation comparison. AJR Am J Roentgenol 2007;188:122-9. [PMID: 17179354]
  120. Yeshwant SC, Summers RM, Yao J, Brickman DS, Choi JR, Pickhardt PJ. Polyps: linear and volumetric measurement at CT colonography. Radiology 2006;241:802-11. [PMID: 17114627]
  121. Halligan S, Taylor SA. CT colonography: results and limitations. Eur J Radiol 2007;61:400-8. [PMID: 17174055]
  122. Burling D, Halligan S, Atchley J, Dhingsar R, Guest P, Hayward S, et al. CT colonography: interpretative performance in a non-academic environment. Clin Radiol 2007;62:424-9; discussion 430-1. [PMID: 17398266]
  123. Barnes E. ACRIN trial shows VC ready for widespread use. 28 September 2007.Accessed at htpp://www.auntminnie.com/index.asp?Sec=sup&Sub=vco&Pag=dis&ItemId=77711 on 22 October 2007.
  124. Pickhardt PJ, Taylor AJ, Kim DH, Reichelderfer M, Gopal DV, Pfau PR. Screening for colorectal neoplasia with CT colonography: initial experience from the 1st year of coverage by third-party payers. Radiology 2006;241:417-25. [PMID: 16982816]
  125. Rex DK. Virtual colonoscopy: time for some tough questions for radiologists and gastroenterologists [Editorial]. Endoscopy 2000;32:260-3. [PMID: 10718393].
  126. Hara AK. The future of colorectal imaging: computed tomographic colonography. Gastroenterol Clin North Am 2002;31:1045-60. [PMID: 12489277]
  127. Rex DK, Petrini JL, Baron TH, Chak A, Cohen J, Deal SE, et al. ASGE/ACG Taskforce on Quality in Endoscopy Quality indicators for colonoscopy. Am J Gastroenterol 2006;101:873-85. [PMID: 16635231]
  128. van Rijn JC, Reitsma JB, Stoker J, Bossuyt PM, van Deventer SJ, Dekker E. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol 2006;101:343-50. [PMID: 16454841]
  129. Bressler B, Paszat LF, Chen Z, Rothwell DM, Vinden C, Rabeneck L. Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis. Gastroenterology 2007;132:96-102. [PMID: 17241863]
  130. Pignone M. Screening for colorectal cancer in adults. Rockville, MD: Agency for Healthcare Research and Quality; 2002. AHRQ Publication No. 02-S003.
  131. Rockey DC, Paulson E, Niedzwiecki D, Davis W, Bosworth HB, Sanders L, et al. Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet 2005;365:305-11. [PMID: 15664225]
  132. Banerjee S, Van Dam J. CT colonography for colon cancer screening. Gastrointest Endosc 2006;63:121-33. [PMID: 16377329]
  133. CT colonography ("virtual colonoscopy") for colon cancer screening. Chicago: Blue Cross Blue Shield Association; 2004
  134. Sosna J, Morrin MM, Kruskal JB, Lavin PT, Rosen MP, Raptopoulos V. CT colonography of colorectal polyps: a metaanalysis. AJR Am J Roentgenol 2003;181:1593-8. [PMID: 14627580]
  135. National Institute of Health and Clinical Excellence. Computed tomographic colonography. National Institute of Health and Clinical Excellence: 2005. Report no. IPG129.
  136. HAYES. Fecal DNA testing for colorectal cancer screening and monitoring. Lansdale, PA: HAYES; 2002.
  137. Haug U, Brenner H. New stool tests for colorectal cancer screening: a systematic review focusing on performance characteristics and practicalness. Int J Cancer 2005;117:169-76. [PMID: 15880368]
  138. Guideline Development Methods: Information for National Collaborating Centres and Guideline Developers. London: National Institute for Clinical Excellence; 2004.
  139. Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991;44:1271-8. [PMID: 1834807]
  140. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25. [PMID: 14606960]
Current as of: October 2008

Internet Citation: Final Evidence Summary: Colorectal Cancer: Screening. U.S. Preventive Services Task Force. October 2008.
https://www.uspreventiveservicestaskforce.org/Page/Document/final-evidence-summary4/colorectal-cancer-screening

USPSTF Program Office   5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857