Recommendation Statement
This statement summarizes the U.S. Preventive Services Task Force
(USPSTF) recommendation and supporting scientific evidence on
routine use of aspirin or nonsteroidal anti-inflammatory drugs for
the primary prevention of colorectal cancer. The complete information
on which this statement is based, including evidence tables and
references, is available in the accompanying evidence report.
The USPSTF is redesigning its recommendation statement in response
to feedback from primary care clinicians. The USPSTF plans
to release, later in 2007, a new, updated recommendation statement
that is easier to read and incorporates advances in USPSTF
methodology. The recommendation statement below is an interim
version that combines existing language and elements with a new
format. Although the definitions of grades remain the same, other
elements have been revised.
Select for copyright and source information.
Contents
Summary of Recommendation
Clinical Considerations
Discussion
Recommendations of Others
References
Members of the USPSTF
Summary of Recommendation
- The USPSTF recommends against the routine use
of aspirin and nonsteroidal anti-inflammatory drugs
(NSAIDs) to prevent colorectal cancer in individuals at
average risk for colorectal cancer.
Rating: D recommendation.
|
Rationale
Importance: Colorectal cancer represents the third most common
type of cancer in both men and women and is the second
leading cause of cancer-related deaths in the United States.
Recognition of risk status:
The vast majority of cases of colorectal cancer arise
from adenomatous polyps in average-risk individuals older
than 50 years of age.
Benefits of aspirin and 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 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.
USPSTF assessment:
Overall, the USPSTF concluded that harms outweigh
the benefits of aspirin and NSAID use for the prevention
of colorectal cancer.
Clinical Considerations
This recommendation applies to asymptomatic adults
at average risk for colorectal cancer, including those with a
family history of colorectal cancer, and not to individuals
with familial adenomatous polyposis, hereditary nonpolyposis
colon cancer syndromes (Lynch I or II), or a history
of colorectal cancer or adenomas.
Clinicians should continue to discuss aspirin chemoprophylaxis
with patients who are at increased risk for coronary
heart disease, but there is good evidence that low-dose
aspirin used to prevent coronary heart disease (CHD)
events in those at increased risk for CHD does not lead to
a reduced incidence of colorectal cancer. Aspirin use by
patients at increased risk for coronary heart disease has
been shown to reduce all-cause mortality. The evidence
and recommendation statements from the USPSTF for
aspirin chemoprophylaxis can be found on the AHRQ
Web site (http://www.preventiveservices.ahrq.gov).
More than 80% of colorectal cancers arise from adenomatous
polyps. However, most adenomatous polyps will
not progress to cancer. Age represents a major risk factor
for colorectal cancer, with approximately 90% of cases occurring
after age 50 years. Thirty to fifty percent of Americans
older than age 50 will develop adenomatous polyps.
Between 1% and 10% of these polyps will progress to
cancer in 5 to 10 years. The risk for a polyp developing
into cancer depends on the villous architecture, degree of
cytologic dysplasia, size, and total number of polyps.
All persons older than age 50 who are at average risk
for colorectal cancer should be screened for colorectal cancer
regardless of their aspirin or NSAID use. The USPSTF
recommendation on screening for colorectal cancer can be
accessed at http://www.preventiveservices.ahrq.gov.
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Discussion
Burden of Illness
While colorectal cancer represents the third most common
cause of cancer and has the second highest mortality
rate among cancers, incidence is decreasing. Progress in
earlier detection and removal of precancerous polyps
through screening, in addition to improved therapies, may
account for the decreasing mortality rate.1-5
The lifetime
risk for colorectal cancer in the general population is
about 5% to 6%,6 and most cases occur after age 50.
The incidence of colorectal cancer is influenced by family
history. People who have 2 or more first- or second-degree
relatives (or both) with colorectal cancer represent approximately
20% of all people with colorectal cancer7 About
5% to 10% of all cases of colorectal cancer develop in
people with the autosomal dominant conditions of familial
adenomatous polyposis or hereditary nonpolyposis colorectal
cancer, also known as the Lynch syndrome.8
Despite
reductions in incidence of colorectal cancer in all races,
racial and ethnic disparities in incidence and mortality
from colorectal cancer remain. African Americans have
higher colorectal cancer incidence and mortality rates than
all other races.2
Scope
The USPSTF reviewed the evidence on the effect of
aspirin and NSAID use on colorectal cancer incidence and
mortality. It reviewed the evidence on the efficacy of aspirin
and NSAIDs in reducing colorectal adenoma and cancer
incidence, colorectal cancer mortality, and all-cause
mortality, including the dose-dependent effects on these
outcomes, and the harms associated with aspirin and
NSAID use in healthy adults.
Effectiveness of Aspirin and NSAID Use
Colorectal Cancer Incidence
On the basis of randomized, controlled trials (RCTs),
cohort studies, and case-control studies, the USPSTF
found good evidence that low-dose aspirin does not lead to
a reduction in the incidence of colorectal cancer, fair evidence
that higher-dose aspirin and NSAIDs may be associated
with a reduction in the incidence of colorectal cancer,
and fair evidence that aspirin used over longer periods
may be associated with a reduction in the incidence of
colorectal cancer.
The Women's Health Study and the Physicians'
Health Study, both good-quality RCTs, assessed the efficacy
of low-dose aspirin use (100 mg every other day and
325 mg every other day) in decreasing colorectal cancer
incidence and found no improvement in colorectal cancer
incidence.9,10
The Nurses' Health Study, a good-quality cohort
study, found a duration- and dose-dependent response: A
significant benefit in colorectal cancer reduction was not
found until more than a decade of use, and maximum risk
reduction for colorectal cancer occurred at a high dose of
aspirin (more than fourteen 325-mg aspirin tablets per
week). Nurses who took more than 14 aspirin tablets per
week for longer than 10 years had a colorectal cancer relative
risk (RR) of 0.47 (95% CI, 0.31 to 0.71).11
Two
case-control studies12,13 assessed the effect of aspirin
dosing on colorectal cancer incidence and found that only
the highest dose of aspirin (for example, 300 mg and 325
mg per day) in each study resulted in a statistically significant
reduction in colorectal cancer incidence: RR, 0.60
(CI, 0.5 to 0.9);12 RR, 0.60 (CI, 0.4 to 0.9)13.
No RCT examined the effect of NSAIDs on colorectal
cancer incidence. One fair-quality cohort study14 assessed
the effect of NSAIDs on colorectal cancer incidence
and found that patients using NSAIDs for more than 12
months at a moderate dosage (defined as a dosage between
the minimum and maximum recommended dosages)
showed a reduction in colorectal cancer incidence (RR, 0.59 [CI, 0.45 to 0.77]). Four pooled case-control studies
of varying quality13,15-17 showed that regular use of
NSAIDs was associated with reductions in colorectal cancer
incidence (RR, 0.70 [CI, 0.63 to 0.78]). One poor-quality
case-control study18 found that moderate and
high calculated cumulative dosing (.320 mg) of "any
NSAID" was associated with statistically significant reductions
in colorectal cancer incidence (RR for moderate dosing,
0.19 [CI, 0.09 to 0.52]; RR for high dosing, 0.22 [CI,
0.09 to 0.56]).
While not the focus of this recommendation, the
USPSTF assessed the magnitude of effect of aspirin and
NSAID use on the incidence of colorectal adenomas because
adenomatous polyps give rise to most cases of colorectal
cancer. There is fair- to good-quality evidence that
aspirin and NSAID use decreases the incidence of colorectal
adenomas. The Physician's Health Study assessed the
efficacy of low-dose aspirin use in decreasing colorectal adenomas
and found no improvement in the incidence of
colorectal adenomas.10 The Nurses' Health Study assessed
the efficacy of low-dose aspirin in decreasing colorectal
adenomas and found a statistically significant reduction
in the incidence of colorectal adenomas, in which a
higher aspirin dose conferred a greater relative risk reduction.19 Four pooled case-control studies of poor to
good quality found that regular use of NSAIDs was associated
with significant reductions in incidence of colorectal
adenomas.20-23
Colorectal Cancer Mortality
Based on a limited number of studies addressing the
efficacy of aspirin and NSAID use on the reduction of
colorectal cancer mortality, the USPSTF concluded that
there is poor-quality evidence that aspirin and NSAID use
leads to a reduction in colorectal cancer mortality. The
Women's Health Study, a good-quality RCT, found that a
decade's use of low-dose aspirin in healthy women had no
effect on colorectal cancer mortality.9 One fair-quality
cohort study24 revealed a significant decrease in colorectal
cancer mortality following low-dose aspirin administration
(RR, 0.58 [CI, 0.38 to 0.97]). No RCT examining
the effect of NSAIDs on colorectal cancer mortality was
found. One fair-quality cohort study that examined the
effect of NSAIDs on colorectal cancer mortality found no
reduction in this outcome.25
Harms
The USPSTF found good-quality 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.
A meta-analysis26
of 21 RCTs that included all randomized, placebo-controlled
trials listed in the Anti-platelet Trialists Collaboration,
in which a direct aspirin-placebo comparison was
possible, found a pooled odds ratios (OR) of 1.5 to 2.0 for
categories of gastrointestinal bleeding with aspirin use (for
example, hematemesis and melena). A meta-analysis27
of 16 RCTs (14 secondary prevention and 2 primary prevention
trials) found that aspirin treatment was also associated
with an absolute risk increase in hemorrhagic stroke
of 12 events per 10 000 persons (CI, 5 to 20 events; P <
0.001). However, a meta-analysis28 of 5 primary prevention
RCTs examining aspirin chemoprevention in patients
without previously known cardiovascular disease
found that aspirin contributed to a nonsignificant increased
risk for hemorrhagic stroke (summary OR, 1.4 [CI,
0.9 to 2.0]).
There is good-quality evidence on the harms of
NSAIDs. A meta-analysis29 of gastrointestinal complications
of NSAIDs from 16 RCTs, most of which are
good-quality studies, found an OR of 5.36 (CI, 1.79 to
16.1) for perforations, ulcers, and bleeding. A meta-analysis30 of 9 RCTs that compared the efficacy and safety of
valdecoxib with those of NSAIDs or placebo in individuals
with active osteoarthritis or rheumatoid arthritis found a
statistically significant higher rate of clinically significant
renal events for valdecoxib and NSAIDs (2% to 3%) compared
with placebo (0.8%). A nested case-control study31 using Tennessee Medicaid enrollees age 65 years or
older who had been hospitalized with community-acquired
acute renal failure found that, after adjustment for demographic
factors and comorbidity, use of NSAIDs increased
the risk for acute renal failure by 58% (adjusted OR, 1.58
[CI, 1.34 to 1.86]). A meta-analysis32 of 50 RCTs
found that NSAIDs elevated supine mean blood pressure
by 5.0 mm Hg (CI, 1.2 to 8.7 mm Hg).
Recommendations of Others
The American Cancer Society currently does not recommend
aspirin or NSAID use to prevent colorectal cancer
because of potential side effects, especially gastrointestinal
bleeding.33
The American Gastroenterological
Association, the American College of Gastroenterology, the
American College of Physicians, the American Medical Association,
and the National Institutes of Health offer no
recommendations regarding the use of aspirin or NSAIDs
for colorectal cancer prevention.
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References
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10. Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH. Low-dose
aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer
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11. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan
GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory
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12. Rosenberg L, Louik C, Shapiro S. Nonsteroidal antiinflammatory drug use
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13. García-Rodríguez LA, Huerta-Alvarez C. Reduced risk of colorectal cancer
among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory
drugs. Epidemiology 2001;12:88-93.
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Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer
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16. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses,
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18. Peleg II, Lubin MF, Cotsonis GA, Clark WS, Wilcox CM. Long-term use
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19. Chan AT, Giovannucci EL, Schernhammer ES, Colditz GA, Hunter DJ,
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adenoma. Ann Intern Med 2004;140:157-66.
20. Morimoto LM, Newcomb PA, Ulrich CM, Bostick RM, Lais CJ, Potter
JD. Risk factors for hyperplastic and adenomatous polyps: evidence for malignant
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25. Lipworth L, Friis S, Blot WJ, McLaughlin JK, Mellemkjaer L, Johnsen SP,
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26. Roderick PJ, Wilkes HC, Meade TW. The gastrointestinal toxicity of aspirin:
an overview of randomised controlled trials. Br J Clin Pharmacol 1993;35:219-26.
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28. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary
prevention of cardiovascular events: a summary of the evidence for the U.S.
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29. Ofman JJ, MacLean CH, Straus WL, Morton SC, Berger ML, Roth EA, et
al. A metaanalysis of severe upper gastrointestinal complications of nonsteroidal
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30. Edwards JE, McQuay HJ, Moore RA. Efficacy and safety of valdecoxib for
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32. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory
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33. American Cancer Society. Major study debunks aspirin, vitamin E for cancer
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on 26 November 2006.
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Members of the Task Force
Corresponding Author: Ned Calonge, M.D., M.P.H., Chair, U.S. Preventive Services Task Force, c/o Program Director, USPSTF, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, E-mail: uspstf@ahrq.gov.
Members of the U.S. Preventive Services Task Force*: Ned Calonge, M.D., M.P.H., Chair, USPSTF (Chief Medical Officer and State Epidemiologist, Colorado Department of Public Health and Environment, Denver, CO); Diana B. Petitti, M.D., M.P.H. , Vice-chair, USPSTF (Senior Scientific Advisor for Health Policy and Medicine, Regional Administration, Kaiser Permanente Southern California, Pasadena, CA); Thomas G. DeWitt, M.D. (Carl Weihl Professor of Pediatrics and Director of the Division of General and Community Pediatrics, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH); Leon Gordis, M.D., M.P.H., Dr.P.H. (Professor, Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kimberly D. Gregory, M.D., M.P.H. (Director, Women's Health Services Research and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA); Russell Harris, M.D., M.P.H. (Professor of Medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); Kenneth W. Kizer, M.D., M.P.H. (President and CEO, National Quality Forum, Washington, DC); Michael L. LeFevre, M.D., M.S.P.H. (Professor, Department of Family and Community Medicine, University of Missouri School of Medicine, Columbia, MO); Carol Loveland-Cherry, Ph.D., R.N. (Executive Associate Dean, Office of Academic Affairs, University of Michigan School of Nursing, Ann Arbor, MI); Lucy N. Marion, Ph.D., R.N. (Dean and Professor, School of Nursing, Medical College of Georgia, Augusta, GA); Virginia A. Moyer, M.D., M.P.H. (Professor, Department of Pediatrics, University of Texas Health Science Center, Houston, TX); Judith K. Ockene, Ph.D. (Professor of Medicine and Chief of Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA); George F. Sawaya, M.D. (Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Epidemiology and Biostatistics, University of California, San Francisco, CA); Albert L. Siu, M.D., M.S.P.H. (Professor and Chairman, Brookdale Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY); Steven M. Teutsch, M.D., M.P.H. (Executive Director, Outcomes Research and Management, Merck & Company, Inc., West Point, PA); and Barbara P. Yawn, M.D., M.Sc. (Director of Research, Olmstead Research Center, Rochester, MN).
*Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to http://www.ahrq.gov/clinic/uspstfab.htm.
Steven M. Teutsch, M.D., M.P. H., was recused from voting on this topic.
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Copyright and Source Information
This document is in the public domain within the United States. For
information on reprinting, contact Randie Siegel, Director, Division of
Printing and Electronic Publishing, 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 to: info@ahrq.gov.
Source: U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the
primary prevention of colorectal cancer: Preventive Services Task Force Recommendation Statement. Ann Intern Med 2007;146(5):361-64.
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Current as of March 2007
Internet Citation:
U.S. Preventive Services Task Force. Routine Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer: Recommendation Statement. March 2007. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf07/aspcolo/aspcolors.htm
540 Gaither Road Rockville, MD 20850