Effects of Non-Selective Non-Steroidal Anti-Inflammatory Drugs on the Aggressiveness of Prostate Cancer

BACKGROUND. Inflammatory mediators have a role in the initiation and progression of prostate cancer. Observed anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) have consisted largely of those that inhibit inflammatory mechanisms thought to promote an aggressive disease phenotype. Epidemiologic studies have supported a chemopreventive effect but there is little research on a possible protective role against prostate cancer aggressiveness and progression to advanced disease. METHODS. We conducted a population-based exploratory study, using cross-sectional and case-cohort approaches to assess, the effect of NSAIDs on indicators of prostate cancer aggressiveness. The study population consisted of 1,619 randomly selected patients with a further over-sampling of 453 prostate cancer mortality cases. All had been curatively treated by radical prostatectomy or external-beam radiotherapy and were sampled using the Ontario Cancer Registry. Aggressiveness of disease at diagnosis, represented by Gleason score, and risk of prostate cancer death were compared across NSAID exposure groups. RESULTS. The adjusted odds ratio (OR) of a total Gleason score of 8-10 versus 2-6 indicated a non-significant protective effect of NSAIDs (OR: 0.74,95% CI: 0.47-1.17). We did not observe an association with risk of prostate cancer death overall (HR: 1.03, 95% CI: 0.79-1.34), but a secondary analysis indicated that NSAID users surviving five years may be protected from early prostate cancer death (HR: 0.54, 95% CI: 0.26-1.13). CONCLUSION. Although estimates were not statistically significant, this exploratory study indicates a possible negative association between NSAID use and disease aggressiveness. Larger investigations with more precise exposure measurements are recommended. Prostate 68: 1655-1665, 2008. (C) 2008 Wiley-Liss, Inc.