Studying the Effects of Low-Dose Aspirin on Prostate Cancer Outcomes

A large Danish registry study found that post-diagnosis use of low-dose aspirin was not associated with a reduced risk of prostate cancer mortality. There was a suggestion of benefit in patients with extended use.

“Regular aspirin use has been suggested to improve prostate cancer survival, but study results are inconclusive,” wrote study authors led by Charlotte Skriver, MSc, of the Danish Cancer Society Research Center in Copenhagen, adding that the larger pooled analyses did not specifically analyze post-diagnosis aspirin use. “Thus, whether post-diagnosis aspirin use has a beneficial effect on the prognosis of prostate cancer, or other cancer types, remains unclear.”

Other research has shown that aspirin can induce apoptosis and reduce growth and cell invasion within prostate tumors. The researchers examined whether post-diagnosis use could thus improve the cancer-specific mortality in a study of 29,136 patients included in a nationwide registry. The results were published in Annals of Internal Medicine.

The cohort had a median age at diagnosis of 70 years, and they were followed for a median of 4.9 years. During that period, 7,633 patients died of prostate cancer, and 5,575 died of other causes. In the year following diagnosis, 7,163 patients (24.6%) used low-dose aspirin, while 21,973 patients (75.4%) did not.

The primary analysis found an adjusted hazard ratio (HR) of 0.95 (95% CI, 0.89–1.01) for prostate cancer mortality in those who used low-dose aspirin. For other-cause mortality, the adjusted HR was 1.12 (95% CI, 1.05–1.20).

In a secondary analysis examining use of aspirin within the 5 and 7.5 years after diagnosis, some suggestion of benefit emerged. For use within 5 years, the adjusted HR was 0.91 (95% CI, 0.83–1.01), and for 7.5 years it was 0.84 (95% CI, 0.72–0.97). In the 5-year analysis, there was no association between duration of use or cumulative dose and added benefit. But in the 7.5-year analysis, the reductions in mortality were greatest among those with long-term use (at least 1,096 days), with an HR of 0.79 (95% CI, 0.67–0.93), and among those with the highest cumulative dose (at least 1,096 tablets), with an HR of 0.77 (95% CI, 0.65–0.91).

“Our study did not support an overall effect of post-diagnosis low-dose aspirin use on prostate cancer mortality,” the authors concluded. “However, our results suggest that low-dose aspirin use might be inversely associated with prostate cancer mortality after 5 years from cancer diagnosis.”

In an accompanying editorial, Teemu J. Murtola, MD, PhD, and Thea Veitonmäki, MD, PhD, of Tampere University Hospital in Finland, wrote that there is a compelling mechanistic reason to believe aspirin might aid in preventing prostate cancer progression. “It is a noncompetitive inhibitor of cyclooxygenase enzyme 1 (COX-1) and also modifies the action of COX-2, an enzyme thought to be important in cancer progression,” they wrote. “From an epidemiologic perspective, however, estimating prostate cancer risk and prognosis among aspirin users is challenging.”

They noted that the suggestion of benefit with longer-term exposure does make sense, given that anti-inflammatory actions likely need time in order to have a meaningful effect on cancer development. However, the minimum required time for such extended effects in colorectal cancer, the malignancy with the most solid evidence for a protective effect of aspirin, is 10 years, rather than the 7.5 years used here. “To determine definitively whether long-term aspirin use improves prostate cancer outcomes, future research should evaluate aspirin exposures longer than those studied to date,” said Murtola and Veitonmäki.