This is the current release of the guideline.

Colorectal cancer

Prevention

Family Practice
Geriatrics
Internal Medicine
Nursing
Preventive Medicine

Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Nurses
Physician Assistants
Physicians

To summarize the U.S. Preventive Services Task Force recommendations and supporting scientific evidence on routine use of aspirin and nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer

Asymptomatic adults at average risk for colorectal cancer, including those with a family history of colorectal cancer

NOTE: This guideline does not apply to individuals with familial adenomatous polyposis, hereditary nonpolyposis colon cancer syndromes (Lynch I or II), or a history of colorectal cancer or adenomas.

Note: The following was considered, but not recommended:

Routine use of aspirin and nonsteroidal anti-inflammatory drugs

Key Question 1A: Does aspirin/nonsteroidal anti-inflammatory drug (NSAID) use in healthy adults (>18 years of age) decrease colorectal cancer (CRC) mortality and/or all-cause mortality?

Key Question 1B: Does aspirin/NSAID use in healthy adults (>18 years of age) decrease CRC incidence?

Key Question 2: What is the magnitude of decreased colorectal adenoma (CRA) incidence due to aspirin/NSAID chemoprevention in healthy adults?

Key Question 3: What is the magnitude of decreased CRA incidence on CRC in healthy adults?

Key Question 4: What is the magnitude of harms of aspirin/NSAID use in healthy adults (i.e., increased major gastrointestinal [GI] bleeding, hemorrhagic stroke, or nephropathy)?

Searches of Electronic Databases

The literature search yielded 1,788 citations. Screening yielded 362 potentially relevant articles that were obtained in full for further review. Of these, 66 studies met the eligibility criteria and were included in the evidence report. More than half of these articles (n=39) were companion or duplicate articles., and nineteen of these were excluded on that basis, as well as two of four studies from different authors with overlapping patient populations. Although excluded, the duplicate and companion articles were used to fill in any missing data not reported in the articles that were used. One study was also excluded because the patient population encompassed a significant proportion of subjects with a personal history of colorectal cancer (CRC). The final study sample included 39 unique studies of effectiveness and five economic evaluations.

Weighting According to a Rating Scheme (Scheme Given)

The U.S. Preventive Services Task Force grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor):

Good

Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.

Fair

Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.

Poor

Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

Review of Published Meta-Analyses
Systematic Review

Note from the National Guideline Clearinghouse (NGC): A focused systematic review of the literature funded by the Centers for Disease Control and Prevention for the Agency for Healthcare Research and Quality was prepared by the University of Ottawa Evidence-based Practice Center (EPC) for use by the U.S. Preventive Services Task Force (USPSTF) (see the "Availability of Companion Documents" field).

Data from included studies was abstracted and their quality assessed. Included studies were grouped based on an a priori defined hierarchy, and statistical pooling was only conducted if clinically and statistically appropriate.

Balance Sheets
Expert Consensus

When the overall quality of the evidence is judged to be good or fair, the U.S. Preventive Services Task Force (USPSTF) proceeds to consider the magnitude of net benefit to be expected from implementation of the preventive service. Determining net benefit requires assessing both the magnitude of benefits and the magnitude of harms and weighing the two.

The USPSTF classifies benefits, harms, and net benefits on a 4-point scale: "substantial," "moderate," "small," and "zero/negative."

"Outcomes tables" (similar to "balance sheets") are the USPSTF's standard resource for estimating the magnitude of benefit. These tables, prepared by the topic teams for use at USPSTF meetings, compare the condition specific outcomes expected for a hypothetical primary care population with and without use of the preventive service. These comparisons may be extended to consider only people of specified age or risk groups or other aspects of implementation. Thus, outcomes tables allow the USPSTF to examine directly how the preventive service affects benefits for various groups.

When evidence on harms is available, the topic teams assess its quality in a manner like that for benefits and include adverse events in the outcomes tables. When few harms data are available, the USPSTF does not assume that harms are small or nonexistent. It recognizes a responsibility to consider which harms are likely and judge their potential frequency and the severity that might ensue from implementing the service. It uses whatever evidence exists to construct a general confidence interval on the 4-point scale (e.g., substantial, moderate, small, and zero/negative).

Value judgments are involved in using the information in an outcomes table to rate either benefits or harms on the USPSTF's 4-point scale. Value judgments are also needed to weigh benefits against harms to arrive at a rating of net benefit.

In making its determinations of net benefit, the USPSTF strives to consider what it believes are the general values of most people. It does this with greater confidence for certain outcomes (e.g., death) about which there is little disagreement about undesirability, but it recognizes that the degree of risk people are willing to accept to avert other outcomes (e.g., cataracts) can vary considerably. When the USPSTF perceives that preferences among individuals vary greatly, and that these variations are sufficient to make the trade-off of benefits and harms a "close-call," then it will often assign a C recommendation (see the "Recommendation Rating Scheme" field). This recommendation indicates the decision is likely to be sensitive to individual patient preferences.

The USPSTF uses its assessment of the evidence and magnitude of net benefit to make recommendations. The general principles the USPSTF follows in making recommendations are outlined in Table 5 of the companion document cited below. The USPSTF liaisons on the topic team compose the first drafts of the recommendations and rationale statements, which the full panel then reviews and edits. Recommendations are based on formal voting procedures that include explicit rules for determining the views of the majority.

From: Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow, CD, Teutsch SM, Atkins D. Current methods of the U.S. Preventive Services Task Force: a review of the process. Methods Work Group, Third U.S. Preventive Services Task Force. Am J Prev Med 2001 Apr;20(3S):21-35.

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms):

A

The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.

B

The USPSTF recommends that clinicians provide [this service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

C

The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

D

The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

I

The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.

Cost Effectiveness

In average-risk populations, and in the context of regular endoscopic screening for colorectal cancer (CRC), nonsteroidal anti-inflammatory drug (NSAID) chemoprevention is presently not cost effective because of the relatively large costs associated with their adverse effects, as well as their relative inefficacy compared with colonoscopy. To be cost-effective, daily aspirin (ASA) use would have to decrease the cardiovascular (CV) mortality by 0.1% or more, and it would have to decrease CRC mortality by at least 30%. Additionally, chemoprevention with COX-2 inhibitors, independent of their newly recognized cardiotoxicity, is expensive and their use as an adjunct to colonoscopy is economically acceptable (i.e., incremental cost-effectiveness ratio [ICER] less than $100,000/life year [LY] saved) if they can prevent CRC mortality by at least 60% and their cost be reduced by at least 75%.

In higher-risk groups, the use of COX-2 inhibitors for chemoprevention of CRC is both less effective and considerably more costly than screening protocols, which are in themselves cost effective by all criteria—their use as an adjunct to screening is economically acceptable if their current cost is considerably reduced and if their efficacy as chemopreventive agents is of at least 50%. These results do not account for any potential CV harms of COX-2 inhibitor use.

Comparison with Guidelines from Other Groups
External Peer Review
Internal Peer Review

Peer Review. Before the U.S. Preventive Services Task Force makes its final determinations about recommendations on a given preventive service, the Evidence-based Practice Center and the Agency for Healthcare Research and Quality send a draft systematic evidence review to 4 to 6 external experts and to federal agencies and professional and disease-based health organizations with interests in the topic. They ask the experts to examine the review critically for accuracy and completeness and to respond to a series of specific questions about the document. After assembling these external review comments and documenting the proposed response to key comments, the topic team presents this information to the Task Force in memo form. In this way, the Task Force can consider these external comments and a final version of the systematic review before it votes on its recommendations about the service. Draft recommendations are then circulated for comment from reviewers representing professional societies, voluntary organizations, and Federal agencies. These comments are discussed before the whole U.S. Preventive Services Task Force before final recommendations are confirmed.

Recommendations of Others. Recommendations regarding the use of aspirin or nonsteroidal anti-inflammatory drug (NSAID) use for prevention of colorectal cancer from the following groups were discussed: The American Cancer Society, the American Gastroenterological Association, the American College of Gastroenterology, the American College of Physicians, the American Medical Association, and the National Institutes of Health.

None available

The type of evidence supporting the recommendations is not specifically stated.

Benefits of Aspirin and Nonsteroidal Anti-inflammatory Drug (NSAID) Use

• There is fair to good evidence that aspirin and NSAIDs, taken in higher doses for longer periods, reduces the incidence of adenomatous polyps.
• There is good evidence that low-dose aspirin does not lead to a reduction in the incidence of colorectal cancer.
• There is fair evidence that aspirin used in doses higher than those recommended for prevention of cardiovascular disease and NSAIDs may be associated with a reduction in the incidence of colorectal cancer.
• There is fair evidence that aspirin used over longer periods may be associated with a reduction in the incidence of colorectal cancer.
• There is poor-quality evidence that aspirin and NSAID use leads to a reduction in colorectal cancer–associated mortality.

Harms of Aspirin and Nonsteroidal Anti-inflammatory Drug (NSAID) Use

• There is good evidence that aspirin increases the incidence of gastrointestinal bleeding in a dose-related manner and fair evidence that aspirin increases the incidence of hemorrhagic stroke.
• There is good evidence that NSAIDs increase the incidence of gastrointestinal bleeding and renal impairment, especially in the elderly.
• There is good evidence that cyclooxygenase-2 inhibitors, a class of NSAID, increase the incidence of renal impairment. Cyclooxygenase-2 inhibitors appear to be associated with an increased risk for cardiovascular events.
• Overall, there is good evidence of at least moderate harms associated with aspirin and NSAIDs.

The U.S. Preventive Services Task Force recommendations are independent of the U.S. government. They do not represent the views of the Agency for Healthcare Research and Quality (AHRQ), the U.S. Department of Health and Human Services, or the U.S. Public Health Service.

Staying Healthy

Effectiveness
Patient-centeredness

Not applicable: The guideline was not adapted from another source.

2007 Mar

United States Preventive Services Task Force - Independent Expert Panel

The U.S. Preventive Services Task Force (USPSTF) is a federally-appointed panel of independent experts. Conclusions of the U.S. Preventive Services Task Force do not necessarily reflect policy of the U.S. Department of Health and Human Services (DHHS) or its agencies.

United States Government

U.S. Preventive Services Task Force (USPSTF)

The U.S. Preventive Services Task Force has an explicit policy concerning conflict of interest. All members of the USPSTF disclose at each meeting if they have an important financial conflict for each topic being discussed. Depending on the nature of the conflict of interest, Task Force members may be recused from voting on recommendations about the topic in question.

This is the current release of the guideline.

This NGC summary was completed by ECRI on February 27, 2007. The information was verified by the guideline developer on March 2, 2007.