USPSTF: The Jury Is Out on Aspirin for CRC Prevention

The US Preventive Services Task Force (USPSTF) has backtracked on low-dose aspirin for the prevention of colorectal cancer (CRC), stating in new guidance that the evidence is too murky to make a recommendation either for or against it.

The group dialed back from its 2016 recommendation because new findings from a handful of trials mean that the evidence is now “unclear whether aspirin use reduces the risk of CRC cancer incidence or mortality.”

However, an expert who was approached for comment disagreed and suggested that aspirin has a role to play in preventing CRC for certain individuals.

The new recommendation on CRC forms only a small part of the latest statement from the Task Force, which was published on April 26 in JAMA.

Much of the new statement, as well as an accompanying editorial, focus on the use of aspirin for the prevention of cardiovascular disease (CVD), as reported by Medscape Medical News.

This latest statement says that the decision to take aspirin is an individual one.

It’s a switch from the group’s advice in 2016, when the Task Force had recommended low-dose aspirin (100 mg/day or less) to prevent CVD as well as CRC for certain adults in their 50s (ie, those at high risk for CVD who had no increased bleeding risk; a life expectancy of at least 10 years; and a willingness to take aspirin every day for at least a decade). At the time, the group called for individual decision-making for adults who fit the bill and who were in their 60s.

Now, the group is recommending individual decision-making from ages 40 to 59 and recommends against aspirin for primary CVD prevention at age 60 and older. It says that the risk of major bleeding outweighs the marginal CVD benefit for older people.

The same document contains recommendations regarding CRC and CVD, then as now, because the randomized trials the group based its advice on ― 13 in the current iteration, spanning 161,680 patients ― collected data on both conditions. The primary focus of those studies was the use of aspirin for CVD prophylaxis, but several studies also included CRC prevention as a more or less secondary outcome.

It was still enough to give the Task Force pause.

Four studies found no association between aspirin use and CRC incidence at up to approximately 10 years of follow-up, note the authors of an accompanying evidence review.

The latest data from one of those trials, the Women’s Health Study (WHS), with almost 40,000 women, did report a lower incidence of CRC at 17.5 years of follow-up, but not afterward out to 26 years. CRC mortality was lower at 17.5 years but was not significantly so and not much after that point.

Another study, the Thrombosis Prevention Trial, which included just over 5000 patients, did find lower CRC mortality at 18.3 years of follow-up.

However, in the ASPREE trial, aspirin was associated with a statistically significantly higher risk of CRC death at 4.7 years (odds ratio, 1.74). Although ASPREE “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 USPSTF says.

The Task Force also noted that data suggesting a long-term CRC benefit with aspirin come mostly from the WHS, which only included women and in which there were just a few CRC deaths upon which to draw its conclusions. In addition, these CRC deaths occurred well after the active phase of the trial had ended, and aspirin use was balancing out between the study arms.

In short, “there was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods,” the review authors conclude.

Pooled analysis of all 13 trials showed that low-dose aspirin was associated with a 58% increase in major gastrointestinal bleeding and a 31% increase in intracranial bleeds, which translated to a 44% increase in the risk of major bleeding.

Brushstrokes Are Too Broad

When asked for comment, Harvard University gastroenterologist Andrew Chan, MD, who has researched aspirin in the prevention of CRC, said he didn’t agree with the Task Force’s assessment.

He criticized the group for not including a number of trials that showed that aspirin reduces the risk of colorectal adenomas, the precursor of most colorectal cancers. The group also left out a trial ― the only aspirin trial in which CRC was a prespecified endpoint ― that showed that aspirin reduced the risk among patients with Lynch syndrome after 10 years.

Given those issues, it would be a mistake, Chan said, to throw the baby out with the bathwater.

“Perhaps it was unrealistic to think that aspirin could be right for everyone, but it doesn’t mean that aspirin doesn’t have a role for the right patient,” he said.

In addition to patients with colorectal adenomas and those with Lynch syndrome, another group who could benefit from aspirin for prevention are younger people at increasing risk for CRC who aren’t included in screening guidelines and who don’t have much risk from iatrogenic bleeding, Chan said.

The Task Force said it wants to see researchers drill down on the long-term impact of aspirin on CRC incidence and mortality and to also take CRC screening into account ― only one trial reported screening rates ― and family CRC history, something none of them addressed.

JAMA. Published online April 26, 2022. Recommendation statement, Full text; Evidence report, Full text

M. Alexander Otto is a physician assistant with a master’s degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is an MIT Knight Science Journalism fellow. Email: [email protected]

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