Aspirin (ASA) likely results in little to no difference in colorectal cancer (CRC) incidence at a follow-up of 5 years to less than 15 years, a review by Chinese investigators reported in The Cochrane Library.

While this venerable old nonsteroidal anti-inflammatory drug (NSAID) may reduce CRC incidence at a follow-up of 15 years or more, the researchers wrote, the evidence is very uncertain, and it may increase CRC mortality at a follow-up of 5 years to less than 10 years — possibly by promoting progression of preexisting, undetected cancers, according to Bo Zhang, MD, a professor in the Gastric Cancer Center at West China Hospital in Chengdu, Sichuan, and colleagues.

They noted that in 2022, CRC ranked third among the most diagnosed malignancies worldwide, with approximately 1.93 million new cases (9.6% of all cancer diagnoses). It is also the second-leading cause of cancer-related mortality, responsible for more than 900,000 deaths (9.3% of all cancer fatalities). In the US, 2025 saw approximately 154,270 new CRC diagnoses and 52,900 CRC-related deaths.

“We initiated this review because the guidelines and primary evidence surrounding aspirin for CRC prevention were becoming increasingly conflicting,” Zhang told Medscape Medical News. “For example, the US Preventive Services Task Force reversed its recommendation for aspirin in primary CRC prevention in 2022, while other societies maintained recommendations for certain groups.”

Furthermore, Zhang added, previous meta-analyses that often mixed high-risk populations (eg, those with Lynch syndrome or a history of adenomas) with the general, average-risk population did not account for the time-dependent nature of ASA’s effects. “We felt a rigorous, time-stratified Cochrane Review focused strictly on the general population was urgently needed to synthesize conflicting data and clear up this confusion.”

The Review

This Cochrane Review, which synthesized evidence from 10 eligible randomized controlled trials (RCTs) comprising almost 125,000 people, evaluated the benefits and harms of ASA compared with placebo or no treatment. All trials were conducted in high-income countries: the US, UK, Australia, and Japan.

Acknowledging considerable risk for bias among the studies, Zhang’s group assessed the certainty of the evidence, which ranged from very low to high. The studies, retrieved from databases in March 2025, included parallel-group or factorial-design RCTs comparing ASA and other NSAIDs with no or a different treatment for preventing CRC or colorectal adenomas (CRAs) in the general population. Seven tested low-dose ASA of 75-100 mg daily, and three tested higher doses. None of the selected trials evaluated other NSAIDs for preventing CRC.

Among the findings:

• ASA may result in little to no difference in CRA incidence at a follow-up of 5-10 years, with hazard ratios varying across studies from 0.95 and 1.00 to 1.17, but the evidence is very uncertain. It may decrease the number of new CRCs after 15 years.
• The agent appears to result in little to no difference in CRC mortality at follow-up of 10 to less than 15 years but may reduce CRC mortality at a follow-up of 15 years or more.
• This NSAID may increase mortality at earlier follow-up of 5 years or more to less than 10 years but may result in little to no difference in mortality at follow-up of 10 years or more. It may, however, reduce mortality at follow-up of 15 years or more.
• While ASA probably results in little to no overall difference in serious adverse events, it does increase the risk for extracranial hemorrhage and probably leads to more hemorrhagic stroke.

As to a possible mechanism for promoting the progression of undetected CRCs, Zhang explained, ASA might inadvertently blunt or suppress antitumor inflammatory or immune responses that normally help keep preexisting occult cancers in check. “By suppressing this immune surveillance, aspirin might accelerate the growth and metastasis of advanced malignancies that were already present but undiagnosed when the patient started taking the drug.”

Overall, these findings give gastroenterologists and primary care physicians the evidence base they need to move away from a “one-size-fits-all” approach and to accept that ASA is not a quick fix for CRC prevention, Zhang said. “The key takeaway is that any potential cancer prevention benefit is delayed by over a decade and is highly uncertain, whereas the bleeding risks are well established.”

As is standard practice for Cochrane Reviews, Zhang’s group will continue to monitor the landscape and update this review when significant new research, such as extended follow-up data from existing large-scale trials, becomes available.

In the meantime, Zhang’s primary message is that clinical decisions regarding ASA must revert to a careful, individualized balancing of a patient’s established cardiovascular risk against their risk for bleeding. “The potential for CRC prevention is currently too delayed, and the evidence too uncertain, to be the primary driver for prescribing aspirin to an average-risk patient today,” he said.

Offering a US gastroenterologist’s perspective on the findings, Aasma Shaukat, MD, director of outcomes research for the Division of Gastroenterology and Hepatology at NYU Langone Health in New York City, said the systematic review adds to other recent studies showing minimal or no benefits of ASA in preventing CRC, CRC mortality, or adenomas.

“The findings align with most recent guidance in the US, which recommends against the use of ASA for CRC prevention,” she told Medscape Medical News. “They may help dispel false expectations of ASA. Many patients still believe ASA can reduce the risk of adenomas and CRC.”

This Cochrane Review was funded in part by the China Postdoctoral Science Foundation.

The authors and Shaukat declared no conflicts of interest.