Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk

Abstract

Background Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal antiinflammatory drugs (NSAIDs). Methods Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden.Results The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). Conclusions This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.

Decreased biochemical progression in patients with castration‑resistant prostate cancer using a novel mefenamic acid anti‑inflammatory therapy: A randomized controlled trial

“…Preclinical and clinical trials have demonstrated that the administration of certain NSAIDs, such as celecoxib does not produce a therapeutic effect (54,55). However, there are reports stating that chronic aspirin consumption lowered PSA levels in patients by 5-10% at the time of PCa diagnosis, compared with patients that did not take aspirin (25,27,29). To the best of our knowledge, the mechanism by which aspirin decreases PSA levels at the time of diagnosis has not yet been determined, nor has whether that effect is associated with disease progression (56)(57)(58).…”

“…Anti-inflammatory agents are currently being investigated as a treatment option in different types of neoplasia, such as lung, cervix, ovarian, colon and gastric cancer (24). Inflammation is observed in numerous pathologies, and the current available data demonstrate that it is a critical component in the origin, proliferation and dissemination of different types of cancer, including PCa (25). In PCa, there is evidence of inflammation in the processes of DNA damage, tumor progression and tumor expansion.…”

“…In PCa, there is evidence of inflammation in the processes of DNA damage, tumor progression and tumor expansion. Hence, sustained use of nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as a mechanism that may retard PCa disease progression by decreasing the inflammatory response in PCa cells (25). Observational studies have revealed that NSAIDs are associated with a lower risk of developing PCa (25) and a lower risk of progression to high-grade PCa (26,27), resulting in different NSAIDs being postulated for the treatment of PCa.…”

“…Hence, sustained use of nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as a mechanism that may retard PCa disease progression by decreasing the inflammatory response in PCa cells (25). Observational studies have revealed that NSAIDs are associated with a lower risk of developing PCa (25) and a lower risk of progression to high-grade PCa (26,27), resulting in different NSAIDs being postulated for the treatment of PCa. Clinical trials have been performed with certain NSAIDs (celecoxib, ibuprofen and indomethacin) (5,28), with unsatisfactory results, upon analyzing endpoints such as PSA levels, tumor size or overall survival time (29,30).…”

Eicosanoids in carcinogenesis

“…Aspirin was shown to be effective in the precancerous adenomatosis polyposis coli or APC [152] and in terms of adenoma prior to CRC [153]. Effective aspirin use against cancers had been shown in ovarian [154,155], stomach [156][157][158], pancreas [159,160], hepatocellular carcinoma (HCC) [161], breast [162,163], prostate [164][165][166], melanoma [167] and mesothelioma [168]. Furthermore, aspirin seems to be effective in inflammatory diseases such as Alzheimer's [169] as well as in obesity, as morbid obesity increased cancer risk was reduced in those patients taking aspirin [170].…”