Final Research Plan

Colorectal Cancer: Screening

April 17, 2014

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.

The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from January 9 until February 5, 2014 at 5:00 p.m., ET.

Figure  1 is the proposed analytic framework, which depicts the 3 key questions for the systematic review. Key question 1 addresses the effectiveness of colorectal cancer screening programs in reducing the incidence of colorectal cancer and/or mortality from colorectal cancer. Key question 2 addresses the individual test performance characteristics of each of the screening modalities for the detection of colorectal cancer and/or adenomas. The screening modalities include the following tests: colonoscopy, flexible sigmoidoscopy, computed tomography colonography, fecal screening tests (such as high-sensitivity guaiac fecal occult blood test, fecal immunochemical test, fecal DNA tests), and the circulating methylated septin 9 DNA blood test. Key question 3 addresses the adverse effects of colorectal cancer screening programs and of the individual screening modalities.

Abbreviations: CT = computed tomography; FIT = fecal immunochemical test; Flex Sig = flexible sigmoidoscopy; gFOBT = Guaiac fecal occult blood test; mSEPT9 = circulating methylated septin 9 DNA.

  1. What is the effectiveness (or comparative effectiveness) of screening programs based on any of the following screening tests (alone or in combination) in reducing a) incidence of and b) mortality from colorectal cancer?
    • Colonoscopy
    • Flexible sigmoidoscopy
    • Computed tomography (CT) colonography
    • Fecal screening tests:
      • Guaiac fecal occult blood test (gFOBT)
      • Fecal immunochemical test (FIT)
      • Fecal DNA test
    • Blood screening test:
      • Circulating methylated septin 9 DNA (mSEPT9)
  2. What are the test performance characteristics (e.g., sensitivity and specificity) of the following screening tests (alone or in combination) for detecting a) colorectal cancer, b) advanced adenomas, and c) adenomatous polyps based on size?
    • Colonoscopy
    • Flexible sigmoidoscopy
    • CT colonography
    • Fecal screening tests:
      • High-sensitivity gFOBT
      • FIT
      • Fecal DNA test
    • Blood screening test:
      • mSEPT9
  3. a) What are the adverse effects (i.e., serious harms) of the different screening tests (either as a single application or in a screening program)?
    b) Do adverse effects vary by important subpopulations (e.g., by age)?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What are the current rates of overall screening for colorectal cancer and screening with specific tests in the United States?
  2. What is the adherence to testing for each of the currently available screening tests? What is the adherence to followup diagnostic colonoscopy for abnormal screening test results (i.e., fecal testing, flexible sigmoidoscopy, CT colonography)?
  3. Do rates of screening or adherence to screening tests vary by important subpopulations (i.e., by age, sex, race/ethnicity)?
  4. What is the likelihood of progression or regression of small adenomas (i.e., measuring 6 to 9 mm) to colorectal cancer?
  5. Does the natural history (progression or regression) of adenomas vary by race/ethnicity?
  6. What is the distribution of colorectal lesions (colorectal cancer, advanced adenomas, small adenomatous polyps) by location in the colon (e.g., proximal versus distal colon)?
  7. Does the distribution of lesions in the colon vary by important subpopulations (i.e., by age, sex, race/ethnicity)?
  8. Are there differences in adenoma (and advanced adenoma) prevalence or count by race/ethnicity?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Populations Age ≥40 years, average-risk or unselected populations; screening populations (i.e., asymptomatic) Populations selected for personal or family history of colorectal cancer, known genetic susceptibility syndromes (e.g., Lynch syndrome, familial adenomatous polyposis), or personal history of inflammatory bowel disease; nonscreening populations (e.g., persons who are symptomatic, screen positive, have iron deficiency anemia, or are under surveillance for a previous colorectal lesion)
Settings Settings representative of community practice for flexible sigmoidoscopy and colonoscopy studies; developed countries (i.e., rated “very high” on the Human Development Index) Primarily research-based settings (or select academic settings that would not be applicable to most practice settings) for endoscopy studies (e.g., small studies aimed at evaluating new endoscopy technologies, studies with operator or resource characteristics not applicable to community practice); developing countries
Screening Tests KQ 1: Any program of colorectal screening, including endoscopy, imaging, and fecal or blood testing

KQs 2–3: Colonoscopy; flexible sigmoidoscopy; CT colonography; fecal screening tests, such as gFOBT (e.g., Hemoccult SENSA®), FIT (quantitative and qualitative testing), and fecal DNA test; blood screening tests (i.e., mSEPT9)

KQs 2–3: Hemoccult II (review of test performance and harms limited to high-sensitivity gFOBT); stool testing using in-office digital rectal examination; double contrast barium enema; capsule endoscopy (e.g., PillCam®); magnetic resonance colonography
Comparisons KQ 1: No screening or alternate screening strategy

KQ 2: Diagnostic accuracy studies that use colonoscopy as a reference standard

KQ 3: No comparator necessary


Outcomes KQ 1: Colorectal cancer incidence (by stage), interval colorectal cancer; colorectal cancer–specific or all-cause mortality

KQ 2: Test performance, including sensitivity and specificity (per person); positive and negative predictive value (per person); yield and miss rates (per lesion) for structural examinations (i.e., colonoscopy, flexible sigmoidoscopy, CT colonography)

For detection of colorectal cancer, advanced adenoma (high-grade dysplasia, villous histology, and/or measuring ≥10 mm), and/or adenomatous polyps by size (i.e., measuring ≤5 mm, 6–9 mm, ≥10 mm)

By location in colon (e.g., proximal versus distal)

KQ 3: Serious adverse events requiring unexpected or unwanted medical attention and/or resulting in death (e.g., requiring hospitalization), including but not limited to perforation, major bleeding, severe abdominal symptoms, and cardiovascular events; extra-colonic findings and subsequent diagnostic workup and adverse events from diagnostic testing for incidental findings on CT colonography; radiation exposure per CT colonography examination

KQ 1: Incidence of adenomas or advanced neoplasia (composite outcome of advanced adenomas and colorectal cancer)

KQ 3: Minor adverse events defined as those not necessarily needing or resulting in medical attention (e.g., patient dissatisfaction, anxiety/worry, minor gastrointestinal complaints)

Study Design Fair- to good-quality studies; studies published between January 1, 2008 and May 31, 2014 (bridge searches will be conducted as required to keep review current at time of publication)

KQ 1: Systematic reviews (of included study designs); randomized, controlled trials; selected well-designed controlled clinical trials; cohort studies; or case-control studies

KQ 2: Systematic reviews (of included study designs), trials, cohort or well-conducted nested case-control diagnostic accuracy studies, screening registry studies

KQ 3: Systematic reviews (of included study designs); randomized, controlled trials; controlled clinical trials; large screening registry or database observational studies; cohort studies; systematically selected case series

Poor-quality studies with a fatal flaw; studies with a publication date outside of review window

KQ 1: Decision analyses

KQ 2: Diagnostic accuracy studies without colonoscopy as a reference standard, diagnostic accuracy studies without representation of a full spectrum of disease (e.g., case-control studies, excluded indeterminate results)


The draft Research Plan was posted for public comment on the USPSTF Web site from January 9 to February 5, 2014. In general, the public comments represent an intense interest in colorectal cancer screening. Based on the comments received, the USPSTF and the Evidence-based Practice Center decided to add contextual questions relevant to racial/ethnic disparities in colorectal cancer to determine if starting screening at an earlier age is important for particular subgroups.

The USPSTF has commissioned a decision model to supplement the systematic review of the evidence on colorectal cancer screening, as it did for the previous topic update in 2008. A decision model is a mathematical simulation that projects the health outcomes that result from alternative interventions for prevention, diagnosis, and treatment. For example, a decision model can describe the expected population health outcomes of a clinical preventive service over a lifetime horizon rather than the more limited range of years generally captured by clinical trials. Inputs into the decision model will include data from the systematic evidence review, which will provide the best available information on the linkages between screening and outcomes of interest. In conjunction with the systematic review of the evidence, the decision model will help the Task Force examine how the benefits and harms of colorectal cancer screening strategies may vary by the screening test chosen, different starting and stopping ages, and time interval between screening tests. In sensitivity analyses, the model will also investigate how individual patient factors—such as comorbid conditions and adherence with recommended screening, diagnostic followup, and surveillance strategies—may affect the benefits and harms of different colorectal cancer screening approaches.

For more information about how the USPSTF uses decision models in formulating its recommendations, please refer to the USPSTF procedure manual, available at