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Rostom A, Dube C, Lewin G. Use of Aspirin and NSAIDs to Prevent Colorectal Cancer [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007 Mar. (Evidence Syntheses, No. 45.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Appendix 6. Results: The Impact of NSAID Chemoprevention on FOBT Testing

The use of NSAIDs (both ASA and non-ASA NSAIDs) could increase GI blood loss, either occult or overt. Subjects on NSAIDs could be more likely to undergo lower GI investigations in the years prior to CRC diagnosis, potentially leading to removal of adenomas during that period and, therefore, reducing the risk of an eventual malignancy. Alternatively, the intake of NSAIDs could induce an underlying malignancy to bleed, increasing the likelihood of cancer detection. This issue was addressed in six studies, four cohort studies, 1 4 one case-control study, 5 and one decision analysis. 6 (Table 4)

Table 4. Impact of NSAID intake on cancer detection.

Table 4

Impact of NSAID intake on cancer detection.

In the Nurses' Health study, a prospective cohort of 27,077 average-risk women who underwent lower endoscopy between 1980 and 1998, Chan et al. compared the likelihood of regular ASA use in women with adenomas depending on the presence of manifestations of GI blood loss (either occult or visible blood) as the indication for endoscopy. 1 The multivariate RR of regular ASA use for asymptomatic women with adenoma was 0.74 (0.61–0.90) and 0.71 (0.59–0.86) for symptomatic women with adenoma (NS).

Over a 22-month period, Kahi et al. prospectively assessed 315 consecutive patients referred for a colonoscopy on the basis of a positive FOBT. 4 Patient with overt GI bleeding, those having undergone a colonoscopy within 5 years, and those on anticoagulants were excluded. Finding of lesion that could explain the positive FOBT result was possible in 21% (95% CI 14–28) and 19% (9–29) of regular ASA or NSAID users and non users, respectively (NS). Among regular ASA users, there was no relation between the dose of ASA and the likelihood of colonic findings and is unlikely to explain a positive FOBT result.

In the Health Professionals Follow-up Study, a prospective cohort of 47,900 males throughout the U.S. who underwent lower endoscopy between 1986 and 1992, Giovannucci et al. examined the possibility that subjects with undiagnosed cancers or polyps might have had bleeding, which would have led them to avoid ASA use and artifactually create an inverse association between ASA use and cancer. 2 In fact, men using ASA regularly at the onset of the study had a decreasing risk of CRC over time, negating that potential association.

In a population-based retrospective cohort study of 104,217 subjects aged 65 years or older enrolled in the Tennesse Medicaid Program, Smalley et al. noted that the use of NSAIDs at diagnosis did not affect cancer presentation, with comparable prevalence of anemia, rectal bleeding, abdominal pain, or tumor at stage I or II among NSAID users and nonusers. 3 They also noted that the adjusted RR of CRC was significantly reduced in subjects who had used NSAIDs for more than 5 years prior to diagnosis, and who had not undergone any lower GI investigations, negating the possibility that the observed protective effect of NSAID use was due to an increased likelihood of undergoing lower GI testing.

In a case-control study of 637 average-risk U.S. subjects undergoing lower endoscopy, Martinez reported that occult blood in the stools was an indication for endoscopy in 9.9% and 10.3% of NSAID users and nonusers, respectively (NS), and that the corresponding figures for rectal bleeding were 17.4% and 17.9% (NS). 5

Ladabaum et al. used decision analysis to examine the effect of increased sensitivity and decreased specificity for FOBT in average-risk U.S. subjects taking ASA. 6 When sensitivities for CRC or CRA were as extreme as 70% and 20%, respectively, and when specificity was as low as 85%, the addition of ASA to a screening strategy of yearly FOBT plus flexible sigmoidoscopy every 5 years slightly decreased CRC mortality rates, slightly increased screening-related mortality rates, and marginally increased costs.

In summary, we could not find any evidence of a detection bias to explain the chemoprotective effect of NSAID.


Chan AT, Giovannucci EL, Schernhammer ES. et al. A prospective study of aspirin use and the risk for colorectal adenoma. Ann Intern Med. 2004;140(3):157–166. [PubMed: 14757613]
Giovannucci E, Rimm EB, Stampfer MJ. et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994;121(4):241–246. [PubMed: 8037405]
Smalley W, Ray WA, Daugherty J. et al. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med. 1999;159(2):161–166. [PubMed: 9927099]
Kahi CJ, Imperiale TF. Do aspirin and nonsteroidal anti-inflammatory drugs cause false-positive fecal occult blood test results? A prospective study in a cohort of veterans. Am J Med. 2004;117(11):837–841. [PubMed: 15589487]
Martinez ME, McPherson RS, Levin B. et al. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of colorectal adenomatous polyps among endoscoped individuals. Cancer Epidemiol Biomarkers Prev. 1995;4(7):703–707. [PubMed: 8672985]
Ladabaum U, Chopra CL, Huang G. et al. Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer. A cost-effectiveness analysis. Ann Intern Med. 2001;135(9):769–781. [PubMed: 11694102]
Cover of Use of Aspirin and NSAIDs to Prevent Colorectal Cancer
Use of Aspirin and NSAIDs to Prevent Colorectal Cancer [Internet].
Evidence Syntheses, No. 45.
Rostom A, Dube C, Lewin G.


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