Abstract PR04: Aspirin, NSAIDs, and risk of prostate cancer: Results from the REDUCE study
Authors: Vidal Adriana C. , Howard Lauren E , Moreira Daniel M , Castro-Santamaria Ramiro , Andriole Gerald L , Freedland Stephen J 
Published: October 2015

Abstract
Background: A recent meta-analysis showed aspirin was associated with a reduced risk of total prostate cancer (PC) however the effect of non-aspirin NSAIDs on PC appeared to vary by geographic region. In North America non-aspirin NSAIDs were null to protective while studies from Europe found either null or positive associations between PC and any NSAIDs use. However, as anti-inflammatory medications can alter PSA levels, which is the chief driver of PC detection, whether these findings reflect reduced detection of PC or truly a biological link with lower PC risk is unknown. We tested the association between aspirin and non-aspirin NSAIDs on PC diagnosis among men with an elevated PSA and negative pre-study biopsy in the REDUCE study where all men received biopsies at 2- and 4-years regardless of PSA levels.
Methods: The REDUCE study tested dutasteride for PC risk reduction in men with a PSA of 2.5-10.0 ng/mL and a negative pre-study biopsy. Study participants for this analysis included 6,427 men who underwent at least one on-study biopsy. The association between use of aspirin, NSAIDs or both, and risk of total and low-grade (Gleason &lt;7) or high-grade (Gleason ≥7) PC vs. no PC was examined using multinomial logistic regression as well as stratified analysis by geographic region (Europe vs. North America) and treatment arm.
Results: Overall, 3,189 men (50%) were non-users, 1,377 (21%) aspirin users, 1,181 (18%) NSAIDs users, and 680 (11%) used both aspirin and NSAIDs. In univariable analysis, aspirin use was associated with lower risk of total PC (OR=0.85, p=0.04), but no associations were found for NSAIDs use (OR=0.74, p=0.08). In multivariable analyses, aspirin use and NSAIDs use was not associated with total, low- or high-grade PC (all p&gt;0.09). However, as the multivariable ORs for both aspirin, NSAIDs, and the combination group were very similar for all outcomes and all suggestive of a slightly lower risk (OR 0.84-0.95), we combined these groups creating a dichotomous variable of aspirin/NSAID user vs. not. When this was done, the use of aspirin and/or NSAIDs was linked with lower risk of total (OR=0.86, p=0.01) and high-grade PC (OR=0.82, p=0.05) in unadjusted analysis. After adjusting for key covariates, the use of aspirin and/or NSAIDs remained associated with decreased risk of total PC (OR=0.87, p=0.02) but not with low- (OR=0.91, p=0.22) or high-grade PC (OR=0.85, p=0.14), though the ORs for low- and high-grade PC were similar to the OR for overall PC. When analyses were stratified by geographic region the association between intake of aspirin, NSAIDs, both, or either (i.e. the dichotomous variable of any aspirin and/or NSAID) and reduced risk of PC was similar in Europe and North America (p-interaction&gt;0.41). Results were similar in placebo and dutasteride treated men.
Conclusions: Among men in the REDUCE study the use of either aspirin and/or NSAIDs was associated with decreased risk of total PC. These data provide further support to the hypothesis that anti-inflammatory drugs may help reduce the risk of PC. Prospective clinical trials to test this hypothesis are warranted.
Citation Format: Adriana C. Vidal, Lauren E Howard, Daniel M Moreira, Ramiro Castro-Santamaria, Gerald L Andriole, Stephen J Freedland. Aspirin, NSAIDs, and risk of prostate cancer: Results from the REDUCE study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR04.