Aspirin cancer advice questioned

5 minute read

The withdrawal of a recommendation for low dose aspirin to prevent colorectal cancer has been criticised by a leading specialist, but another says the evidence can’t be ignored.

Cancer experts are divided about the withdrawal of a recommendation for low dose aspirin as a preventive measure for colorectal cancer.

A leading oncologist says reliance on the wrong research led to the move, while a researcher from one of the main studies says the evidence “can’t be ignored.”

The US Preventative Services Task Force (USPSTF) recommendation from 2016 advised “initiating low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.” For those between 60 and 69, the decision “should be an individual one”, and there was insufficient evidence either way for those under 50 or over 69.

But a systemic review of new trial results and a commissioned modelling study led the task force to conclude in 2022 that “the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality.”

They also shifted the age range for CVD recommendations, stating that low dose aspirin should be an individual decision for 40 to 59-year-olds with a 10% or greater 10-year CVD risk, and is not recommended for those 60 and over.

The task force relied on four randomised control trials for its recommendations on colorectal cancer, only two of which reported on colorectal cancer mortality during the trial. And one of those, ASPREE, found that aspirin use was actually associated with statistically significant higher mortality rates at follow-up just shy of five years.

“Although this finding does not constitute firm evidence that aspirin use is associated with increased risk of CRC mortality, it is one factor that calls into question whether aspirin use has a beneficial effect on CRC outcomes,” the authors wrote.

“Longer-term follow-up data suggesting that aspirin use is associated with lower CRC risk is heavily weighted by one trial conducted in women only, and the evidence on CRC mortality is limited by few CRC deaths.”

But Professor Andrew T Chan, director of cancer epidemiology at the Mass General Cancer Center and a professor at Harvard Medical School, said that was a “narrow interpretation” of the findings.

“In its effort to offer simplified, broad-based recommendations, the USPSTF may have instead muddied the waters, thereby impeding progress in defining the appropriate role for aspirin for CRC prevention, a missed opportunity for the field of cancer prevention,” he said.

Writing in the Journal of the American Medical Association, Professor Chan questioned the task force’s reliance on three studies, ASCEND, ARRIVE and ASPREE, saying their duration of around five to 7.5 years was “too brief for a protective benefit of aspirin to emerge”.

And the Women’s Health Study finding that a lower incidence of CRC at 17.5 years did not continue at 26 years “should not be surprising… based on cohort attrition and the potential influence of increasing post-trial self-selected aspirin use over time,” he said.

Professor Chan was particularly critical of the USPSTF’s weighting of the findings of the ASPREE trial, which looked at US and Australian participants aged 65 and older.

“ASPREE did not specify CRC mortality as an end point, included only a small number of events, and did not adjust analyses for comparisons,” he pointed out.

Professor Chan, who was himself a co-principal investigator in the ASPREE trial, said that a subsequent study from the trial found aspirin did not increase the incidence of overall cancer or CRC.

In addition, he noted that the ASPREE trial cohort was older to begin with.

“It is not surprising that starting aspirin at an older age might be too late to influence cancer-initiating events that occur in mid adulthood,” he wrote.

A recent study Dr Chan was involved in that pooled data of nearly 95,000 participants from two cohort studies, followed up for over 40 years, found aspirin was associated with lower risk of CRC only in participants who started regular use before the age of 70.

“The USPSTF’s focus on ASPREE’s outlier finding seems an overreach,” he said.

But ASPREE’s cancer lead, medical oncologist Professor Peter Gibbs, disagreed with Professor Chan’s interpretation of the data.

He said he believed the updated recommendations were appropriate and that the trial’s controversial findings about increased cancer deaths could not be brushed off.

“It’s a very big clinical trial with a strong hazard ratio. And statistically, it’s a sound finding,” he told Oncology Republic.

“People on aspirin aren’t more often diagnosed with cancer, but if they are diagnosed, their cancer behaves more aggressively. It grows faster and is less responsive to treatment. We can’t explain that finding, but it’s a randomised clinical trial, so you can’t ignore it.”

The link between aspirin and cancer prevention has only been shown in a prospective randomised trial in people with Lynch syndrome, Professor Gibbs pointed out.

“Beyond that, we don’t have any randomised trial data in the younger, fitter population,” he said.

The question is whether or not aspirin has a different effect depending on age, said Professor Gibbs.

“Bottom line is we don’t know,” he said.

Apart from the small Lynch syndrome subset, he doesn’t think there is strong evidence that aspirin prevents cancer development, but there is evidence that it could increase cancer death in older people.

The recommendations were important for clinical practice, Professor Gibbs emphasised.

“There are people that start on aspirin because they think it’s beneficial, and then they run into trouble because it’s not a harmless, low risk drug. People can get bleeding and ulcers and other things from using it,” he said.

“Aspirin does have side effects that can be significant. And in the absence of convincing evidence of benefit, we need to be a little bit careful.”

JAMA 2022, Online 28 July

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