Efficacy and harm of aspirin treatment for colorectal cancer

Articles by Master, Doctor Mai Vien Phuong - Gastroenterologist - Department of Medical Examination & Internal Medicine - Vinmec Central Park International General Hospital.

The authors suggest low-dose aspirin use in people aged 50-69 years with a ≥10% risk of cardiovascular disease over the next 10 years, who do not have an increased risk of bleeding and are willing to take aspirin less at least 10 years to reduce colorectal cancer risk.
The authors recommend that aspirin should not be used as a substitute for colorectal cancer screening.

Many long-term studies demonstrate the benefit of aspirin in reducing colorectal cancer incidence and mortality. In 2016, the Foundation for Disease Control and Prevention conducted a systematic review and analysis of primary and secondary cardiovascular disease prevention trials to evaluate the impact of aspirin on morbidity and mortality. death from colorectal cancer. They found no effect on colorectal cancer risk within 10 years of aspirin treatment in 69,535 subjects (RR 0.99, 0.85–1.15) despite the following analyzes in 47,464 subjects. 10–19 years of initiation of aspirin showed a 40% reduction in colorectal cancer risk (RR 0.60, 0.47–0.76).
However, it is important to note that the included studies generally do not report or break down the results by the individuals' colorectal cancer screening histories collected. Although the authors have solid evidence that colorectal cancer screening reduces morbidity and mortality, it remains unclear whether long-term aspirin use provides further increased benefit and whether the benefits outweigh the harms. Although most of the large pharmacological intervention trials included in the review were conducted before universal screening. The American Women's Health Study reported a nearly 50% screening rate and reduced rates of colorectal cancer with aspirin use. This study randomized 39,876 women in the United States to either 100 mg aspirin every other day or a placebo. The average age of the participants was 55 years old. After a median follow-up of 10.1 years, no effect of aspirin on colorectal cancer incidence was observed (RR 0.97, 0.77–1.24). During the 18-year follow-up of this cohort, a reduction in colorectal cancer incidence was observed in the aspirin group (HR 0.80, 0.67–0.97), particularly due to a reduction in colorectal cancer. right colon (HR 0.73, 0.55–0.95). When the analysis was limited to postoperative events, the delayed effect of aspirin was increased (HR 0.58, 0.42–0.80). Therefore, it is reasonable to assume that aspirin is beneficial in reducing the risk of colon cancer in the screened and unscreened groups. Another caveat to consider is that the actual benefits of aspirin and screening depend on compliance, and those who adhere to screening may also be those who are likely to take aspirin for at least 10 years or longer. .

In a Physician's Health study, 22,071 healthy male physicians aged 40–84 years were randomized to aspirin 325 mg every other day versus placebo for 5 years. The study found no association between aspirin and colorectal cancer (RR 1.15, 0.80–1.65).
The Iowa Women's Health Study was a prospective cohort study of 41,836 postmenopausal women aged 55–69 years at baseline. Compared with never-users of aspirin, ever-use of aspirin was associated with a lower risk of colon cancer in women who reported 2–5 times aspirin use (HR 0.79, 0.59 –1.04) and > 6 times per week (HR 0.76, 0.58–1.00), respectively. The effect was driven by a reduction in proximal colon cancer (HR 0.67, 0.51–0.87) in those who reported using aspirin >2 per week compared with those who did not. No association was found between colon or distal rectal cancer and aspirin.

A 32-year follow-up of the Nurses' Health Study and the Health Professionals Follow-up Study including 135,965 healthcare professionals (88,084 women and 47,881 men, respectively) reported the use of take aspirin every two years. Compared with occasional use, regular aspirin use (defined as reported aspirin use at least 2 times per week, including both standard and low-dose aspirin) was associated with an increased risk of cancer. colorectal cancer was lower (RR 0.81, 0.75–0.88), including in women (RR 0.84, 0.76–0.93) and men (RR 0.77, 0). ,68–0.87). The minimum duration of regular use associated with lower risk was 6 years, and the association increased with duration of use RR 0.86 (0.78–0.94) for 6–10 years, and RR 0.76 (0.69–0.84) for > 16 years.
A 20-year follow-up of 5 randomized cardiovascular disease prevention trials confirms that aspirin is associated with a reduction in colorectal cancer mortality (HR 0.61, 0.43–0.87). . Accordingly, the risk of colorectal cancer decreased with scheduled aspirin use, from ≥2.5 years (HR 0.54, 0.36–0.80) to ≥5 years (HR 0.48) , 0.30–0.77). Similar benefits were seen with aspirin doses greater than 75 mg per day. The risk of dying from colorectal cancer was increased in subjects allotted 30 mg compared with 283 mg per day in the Dutch TIA trial (OR 2.02, 0.70–6.05).
In a case-control study from the UK, aspirin users had a lower risk of colorectal cancer mortality (RR 0.68.0.56–0.82), which was related to stage less advanced colorectal cancer at the time of diagnosis: Dukes B (RR 0.54, 0.42–0.68), Dukes C (RR 0.71.0.56–0.91) and Dukes D (RR 0.60, 0.48–0.74).

The United States Foundation for Disease Control and Prevention's systematic review of bleeding events from 10 primary prevention trials of cardiovascular disease in adults (mean age, 53.2–70.1 years) was refers to the risk of major gastrointestinal or intracranial bleeding. Major gastrointestinal bleeding included those that resulted in death, those requiring hospitalization, blood transfusion, or those described as serious by the trial investigator. Intracerebral hemorrhage includes hemorrhagic stroke and intracerebral, subdural, and subarachnoid hemorrhage. An increased risk of major gastrointestinal bleeding (additional 0.29 cases per 1,000 person-years) and hemorrhagic stroke or other intracranial bleeding (additional 0.11 cases per 1,000 person-years) was observed. .

References
Shaukat, Aasma MD et al. ACG Clinical Guidelines: Screening for Colorectal Cancer 2021. American Journal of Gastroenterology: March 2021 - Volume 116 - Issue 3 - pp. 458-479
Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin 2020;70:145–64.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7–30.