Aspirin and Colorectal Cancer

Bains SJ, Mahic M, Myklebust TÅ, et al. Aspirin as secondary prevention in patients with colorectal cancer: an unselected population-based study. J Clin Oncol. 2016;34(21):2501-2508. 

Observational, population-based, retrospective cohort study

To assess whether use of aspirin in those with a history of colorectal cancer (CRC) affects overall survival or CRC-specific survival

The study took place in Norway using government health databases for history of CRC, aspirin usage (aspirin is prescriptive in Norway), and causes of death. This system provides a randomized cohort through inclusion of consecutive patients fitting the criteria, encryption of personal information, and a validated means of obtaining relevant data with almost no one lost to follow-up. Participants were those diagnosed with CRC between January 2004 and December 2011. Patients with any stage (from stage I to stage IV) who had only one diagnosis of CRC and had histological evidence of adenocarcinoma with known topography (site of tumor involvement) were included. There were 23,162 participants who met criteria for analysis, and 88.9% of all participants underwent surgical resection of their tumors. All participants were over 18 years of age (mean=71.5 years).

Retrospective use of enteric coated aspirin, either 75 mg per day or 160 mg per day, as determined by The Norwegian Prescription Database 

Participants who used aspirin for at least 6 months (n=6,102) were compared to those who did not use aspirin (those who filled less than 3 prescriptions were considered nonusers; n=17,060). In a subset analysis, the group who used aspirin both before and after CRC diagnosis (pre-and post-diagnosis users; n=4,391) were analyzed separately from the group who only used aspirin after diagnosis (post-diagnosis users; n=1,711) and each group compared to the group of aspirin nonusers. The data analysis excluded the first 30 days post-resection to remove surgical complications as cause of death. Participant inclusion continued until death, emigration, or study conclusion date (December, 2013).  

There were a total of 2,071 deaths from all causes (32.9%), and 1,158 (19%) of those were due to CRC in aspirin users (n=6,102). Among the aspirin nonusers (n=17,060) there were 7,218 (42.3%) deaths due to all causes with 5,375 (31.5%) CRC-specific deaths. In multivariable analysis, aspirin use was associated with a 15 % reduced risk of CRC-specific death (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.79-0.92; P<0.001) and a downward trend in the risk of death by any cause by 5% (HR: 0.95; 95% CI: 0.90-1.01; P=0.076). This effect was more pronounced in those who took aspirin both before and after their diagnosis of CRC; they had a 23% improvement in CRC-specific survival (HR: 0.77; 95% CI: 0.71-0.84; P<0.001) and a 14% improvement in overall survival (HR: 0.86; 95% CI: 0.81-0.92; P<0.001). Through the use of a time-dependent coefficient model, the authors showed that the use of aspirin was most beneficial in the first 2 to 3 years post-diagnosis.

According to the National Cancer Institute, an estimated 1.3 million cases of CRC are diagnosed annually worldwide. In the United States, screening has reduced both the incidence and mortality of CRC.¹ Despite this limited success, CRC still remains the third most common cancer diagnosis in America (behind lung, breast or prostate cancers), and the second most common cause of cancer deaths.¹ Due to its high prevalence, it is likely that every health care practitioner will work with patients who have a history of CRC.

 

Perhaps there is no more simple, yet profound, piece of advice we can offer these patients than to simply take a baby aspirin every day. If this were the only study to date indicating benefit, the advice might ring hollow, especially considering that the aspirin users in this study had some significant tendencies that may have had additive beneficial effects (tumors in the aspirin user group were more likely to be diagnosed at an earlier stage and have less aggressive pathology).

 

This, however, is not the first study to suggest that aspirin has benefit in the prognosis of CRC. In 2009, Chan and colleagues reported results that combined 2 prospective cohorts (1279 men and women) of participants with a history of CRC. They found a 29% reduction in CRC-specific mortality and a 21% reduction in all-cause mortality in CRC patients who took aspirin after a diagnosis (stages I-III).² Chan and colleagues went further, testing for cyclooxygenase (COX)-2 overexpression in the original tumors. They found that there was a 61% reduction in CRC-specific mortality if the tumors overexpressed COX-2 (HR: 0.39; CI: 0.20-0.76). However, in those whose tumors did not overexpress COX-2, no benefit was derived from taking aspirin (HR: 1.22; CI: 0.36- 4.18).

Since Chan’s publication, follow-up studies and reviews have corroborated a beneficial role for the use of aspirin in those with a history of CRC.^3-7 Across these studies, low- dose (81 mg) aspirin confers benefit either by reducing relapse, reducing CRC-specific deaths, and/or reducing all-cause mortality. Of course, the potential benefits of aspirin must be weighed against the risks of easy bruising, internal bleeding of the GI tract, and hemorrhagic risks, including strokes in the elderly.⁸  The finding of an improvement in overall survival with aspirin use in several of these studies should bring some confidence that the benefits outweigh the risks in this survivor population.⁹ However, each patient should be fully informed of the risks and monitored for potential adverse effects of aspirin.

 

Those of us steeped in integrative oncology spend much of our time understanding how diet, the microbiota, sleep, exercise, and mind-body practices affect the risk of cancer or its recurrence. These are all essential pursuits to improve our patients’ current quality of life and longevity. Much of our education and work with each patient involves major changes in diet or lifestyle. Much of it also requires a level of commitment that may or may not be inherent in any given patient.  Ultimately, our goal is to help our patients live well and live long. To this end, we must remember to consider baby aspirin as a simple, evidence-based, non-toxic intervention for our patients with a history of CRC.