Allopurinol and prostate cancer survival in a Finnish population-based cohort

Abstract

Background Allopurinol is gout medication that inhibits uric acid formation. Its possible anti-carcinogenic properties have been under research in past years. Studies based on Taiwanese registries showed that long term allopurinol use might reduce prostate cancer (PCa) incidence. However, our studies based on Finnish registries did not support those findings. In this study, we evaluate whether allopurinol use is associated with prostate cancer-specific survival (CSS) or overall survival (OS) in a Finnish population-based cohort. Methods The study cohort was originally enrolled for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). We included all newly diagnosed PCa cases during 1996–2015, 9252 men in total. Information on allopurinol purchases was from the national prescription registry of the Social Insurance Institution of Finland. Information about deaths, treatments, and use of other medications was obtained from registries, and tumor stage and PSA at diagnosis from medical records. Follow-up started at diagnosis, and we analysed separately two endpoints: PCa-specific death and overall death. We used an extended Cox regression with adjustment for age at diagnosis, Charlson comorbidity index, FinRSPC trial arm, use of other drugs and EAU PCa risk group. Results During a median follow-up of 9.86 years, 2942 deaths occurred, including 883 from PCa. There was no difference in CSS between allopurinol user and non-users, but allopurinol users had lower OS (multivariable-adjusted hazard ratio 1.77; 95% CI: 1.57–2.00). However, this decrease in OS was mitigated along with increasing intensity of allopurinol use. Conclusions We found no marked difference in CSS by allopurinol use. Allopurinol users had lower OS but there were no significant differences by duration or intensity of allopurinol use. Allopurinol use may not have anticancer effects against prostate cancer; instead, it may be a surrogate for metabolic problems causing shorter OS among men with PCa.

Effectiveness of Treatments That Alter Metabolomics in Cancer Patients—A Systematic Review

“…Other different and very useful factors in the development of interventions regarding oncometabolites related with prostate cancer are choline [26], glucose [10], nitric oxide [27] and uric acid [28]. Although these oncometabolites seem related with the severity and mortality in patients suffering from prostate cancer, interventions reducing the presence of for instance uric acid do not show a significant reduction in tumor growth or overall survival [29]. These results show the difficulty in understanding the way cancer cells use oncometabolites to proliferate and progress, making the interpretation of metabolomics essential.…”

Investigating the Anti-inflammatory Effect of Allopurinol on the Prevention of Prostate Cancer

“…Some studies have shown that gout may be associated with prostate cancer [9][10][11]. One study even identified a potential mechanism of the relationship between gout and prostate cancer demonstrating that a change in plasma or intracellular urate levels has an impact on prostate cancer cell growth [12]. This indicated that the use of uric acid-lowering agents, such as Allopurinol, would potentially be therapeutic in the prevention of prostate cancer.…”