PARIS—Contrary to the findings of previous epidemiologic studies, a new study found that use of nonsteroidal anti-inflammatory agents (NSAIDs) is associated with an increased risk of prostate cancer (PCa) overall and aggressive PCa, Finnish researchers reported at the 27th Annual Congress of the European Association of Urology.

A team at the University of Tampere School of Medicine led by Teemu J. Murtola, MD, identified all newly diagnosed PCa cases in Finland during 1995 to 2002 and matched these with 24,657 controls. After adjusting for potential confounders, men who had ever used NSAIDs had a 31% increased risk of PCa overall and a 63% increased risk of advanced PCa.

For the study, Dr. Murtola’s group estimated the cumulative COX-2 inhibition by multiplying the total cumulative amount (in milligrams) of each NSAID used with the drug-specific COX-1/COX-2 inhibition ratios. They also estimated the propensity to NSAID use among users of medications to treat benign prostatic hyperplasia, diabetes, hypercholesterolemia, and hypertension. From this, the researchers calculated a propensity score for each subject.

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The study revealed that NSAID usage is associated with increased PCa risk at the population level regardless of the quantity of COX-2 inhibition caused by the usage.

“The major difference between our study and most of the previous studies is the source of information on NSAID usage,” Dr. Murtola said. “In our study, the information came from a national prescription database, whereas most of the previous studies relied on survey information, i.e., on self-reported data.”

Although the researchers did not have knowledge of over-the-counter NSAID usage—the most common way these drugs are used—their data was far more detailed than in any previous study, enabling them to estimate even the cumulative COX-2 inhibition based on total amount of NSAID use in milligrams.
“Because all NSAIDs in our study were prescribed by a physician, all users for certain had an indication for the usage,” Dr. Murtola said. “We believe this was often some chronic condition possibly associated with chronic systemic inflammation. An example of this could be arthrosis caused by excess obesity. Therefore, the NSAID users in our study likely were, as a group, different from previous studies where most users had been using prescription-free NSAIDs most often in short-term.”
Dr. Murtola and his colleagues said they do not think COX-2 inhibition, by itself, caused the increased PCa risk observed in the study. “If this really were the case, we would have expected dose-dependence between COX-2 inhibition and the risk, but this was not observed,” Dr. Murtola said.

Instead, they believe the elevated risk was caused by underlying comorbidities for which NSAIDs were prescribed. “Therefore, our main message is that COX-2 inhibition by NSAID usage does not decrease prostate cancer risk at population-level,” Dr. Murtola told Renal & Urology News. “Other factors that associate [with] and cause the medication use affect the risk more, leading to net effect of increased risk.”