Take Two Aspirin and Schedule Your Colonoscopy
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington; Dr. Phillips is a retained consultant for Cephalon and Ventus, and serves on the speakers bureau for Cephalon and Boehringer Ingelheim.
Synopsis: For patients with colorectal cancer whose tumors overexpressed COX-2, regular aspirin use was associated with a lower risk of death related to colorectal cancer for about 12 years after initial diagnosis.
Source: Chan AT, et al. Aspirin use and survival after diagnosis of colorectal cancer. JAMA 2009;302:649-658.
The hypothesis of this study was that aspirin use after diagnosis of colorectal cancer is associated with a lower risk of cancer-related death. This report is the result of a prospective, observational study of 1279 individuals (health professionals) who were diagnosed with pathologically confirmed stage I, II, or III colorectal cancer. They were then carefully followed for an average of 11.8 years. The individuals in this cohort (recruited from the Nurses' Health Study and the Health Professionals' Follow-up Study) completed detailed questionnaires every 2 years. Those who were diagnosed with colorectal cancer and who were willing to participate in the current trial also received supplemental questionnaires about their tumor, its treatment, and their lifestyles. At baseline, the mean age of this cohort was about 65 years, mean BMI was about 26 kg/m2, almost all were white, and about two-thirds were women.
The main reasons for aspirin use were different for men and women. Headache and arthritis were the most common reasons that women took aspirin regularly, but cardiovascular disease (presence or prevention) and arthritis were the most common reasons that men did. It is unclear (to this reader) how "regular" aspirin use was defined for this study, because questionnaires variously asked about taking once a week and twice a week.
The 1279 tumors were about equally split among the three stages, and about three-fourths of the tumors were colon cancer, with one-fourth being rectal cancer. The investigators were able to obtain pathologic specimens of the primary tumor for 58% of the participants in the Nurses' Health Study and for 76% of those in the Health Professionals' Follow-up Study. They undertook cyclo-oxygenase 2 (COX-2) tumor expression analysis on all those samples for which adequate tissue was obtained.
Statistical analysis controlled for factors known to influence colorectal cancer survival. The data confirmed that post-diagnosis physical activity was associated with improved survival, but BMI did not affect it.
Over the nearly 12 years of follow-up, there were 480 deaths among the 1729 individuals who were diagnosed with colorectal cancer; 220 of these were due to the colorectal cancer. For the entire cohort, the overall 5-year survival was 88% for those who used aspirin regularly, compared with 83% for those who did not. The 10-year survival rate was 74% for those who used aspirin regularly, compared with 69% for those who did not. Compared with non-aspirin users, regular users appeared to be less physically active, more likely to have formerly smoked, and less likely to be diagnosed with stage III cancer than those who did not use aspirin regularly. The reduction in cancer risk was statistically significant after adjusting for predictors of cancer recurrence. In a separate analysis of those with more advanced cancer, the investigators found that those with stage II and III cancers also had reduced hazard ratios (HRs) for death if they used aspirin regularly. There was a dose-response relationship between aspirin use and cancer survival, with those using 0.5-5 standard aspirin a week having a colon cancer-specific mortality rate of 0.57, and those using 6 or more tablets a week having a rate of 0.49 (P = 0.04). The benefits of aspirin use after tumor diagnosis were unchanged in subanalyses in which the authors excluded those who died within a year of intake into the study, and in which they assessed the effects of receiving adjuvant chemotherapy.
Surprisingly, aspirin use prior to diagnosis was not associated with colorectal cancer-specific mortality or overall mortality, and those who were using aspirin prior to tumor diagnosis who continued to use it after diagnosis did not have a reduction in tumor-related death.
There were 459 study participants for whom COX-2 assays could be done. In these people, the benefit of aspirin use after diagnosis appeared to be confined to those with COX-2-positive tumors, and was substantial (multivariate HR, 0.39; confidence interval, 0.20-0.76). Further, individuals whose tumors were COX-2-positive had improved survival if they took aspirin regularly before diagnosis as well as after (in contrast to the entire cohort, for whom use of aspirin prior to diagnosis seemed to negate the reduced mortality risk associated with taking aspirin post diagnosis).
Commentary
This study suggests that we should advise our patients who are diagnosed with colorectal cancer to take about an aspirin a day (the strongest reduction in death risk was for those taking 6 standard aspirin a week or more), but that it may not be of much benefit if they were already taking aspirin regularly prior to diagnosis or if their tumors do not overexpress COX-2. This work extends a previous study of patients with stage III colon cancer, which showed that regular use of aspirin or of COX-2-selective inhibitors was associated with reduced cancer mortality.1 The current study takes this a step further by assessing the influence of aspirin use prior to diagnosis and by evaluating the effect of COX-2 status on survival. Based on their findings that aspirin use both before and after diagnosis of colorectal cancer (as opposed to aspirin use that was initiated only after the diagnosis) was not associated with improved survival, the authors note, "This suggests that aspirin may have a specific effect on the prevention or progression of micrometastases among individuals with established disease ... . This suggests the possibility that tumors that initially developed despite exposure to aspirin may be less susceptible to any potential effect of aspirin on tumor progression."
They speculate that their findings support the hypothesis that COX-2-positive tumors may be relatively sensitive to the anticancer effect of aspirin, whereas COX-2-negative tumors may be relatively aspirin-resistant.
Does the fact that pre-diagnostic use of aspirin appears to negate its post-diagnostic survival benefit mean that we should not recommend aspirin as chemoprophylaxis against cancer? Many observational studies and randomized trials have shown that aspirin appears to protect against colorectal cancer,2-4 probably because of inhibition of the COX-2 pathway, which is overexpressed in up to 85% of colorectal cancers.5,6 However, despite apparent benefit in reducing risk of cancer development, aspirin (and COX-2 inhibitors, for that matter) are not recommended as chemopreventive agents because of side effects and gastrointestinal bleeding.2
But in the accompanying editorial, Neugut makes the case that recommending aspirin, along with other lifestyle changes, in the "teachable moment" that may accompany a colorectal cancer diagnosis could improve the outcome of those with this tumor.7
References
1. Fuchs C, et al. Influence of regular aspirin use on survival for patients with stage III colon cancer: Findings from intergroup trial CALGB 89803 [abstract]. J Clin Oncol 2005;23(suppl 16):3530.
2. Dubé C, et al; U.S. Preventive Services Task Force. The use of aspirin for primary prevention of colorectal cancer: A systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007; 146:365-375.
3. Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348: 891-899.
4. Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883-890.
5. Ogino S, et al. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res 2008;14:8221-8227.
6. Brown JR, DuBois RN. COX-2: A molecular target for colorectal cancer prevention. J Clin Oncol 2005;23: 2840-2855.
7. Neugut AI. Aspirin as adjuvant therapy for colorectal cancer: A promising new twist for an old drug. JAMA 2009;302:688-689.
For patients with colorectal cancer whose tumors overexpressed COX-2, regular aspirin use was associated with a lower risk of death related to colorectal cancer for about 12 years after initial diagnosis.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content