Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.
Dr. Peter S. Liang
That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.
This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.
Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.
Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.
For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.
Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.
No funding sources were reported. The experts reported having no conflicts of interest.