Statins show benefit in Caucasian PCa patients

San Francisco-A study investigating associations between statin use and prostate cancer outcomes provides further evidence that the medication may have race-related benefit, providing protective effects among Caucasian men but not in African-Americans, investigators reported at the AUA annual meeting in San Francisco.

The research was conducted as a follow-up to a previous study that found statin use after radical prostatectomy was associated with reduced risk of biochemical recurrence and that its protective effect was observed in non-African-American men, but not in African-Americans (BJU Int 2014; 114:661-6). The present multicenter study focused on patients who initiated androgen deprivation therapy (ADT) for disease recurrence after radical prostatectomy. It evaluated risks of metastases, castrate-resistant prostate cancer (CRPC), prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM).

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In a multivariable analysis adjusting for demographic, clinical, and pathologic characteristics, no associations were found between pre-ADT statin use and any of the outcomes when considering the overall population. In a race-stratified univariable analysis, statin use prior to ADT was associated with significantly reduced risks for metastasis, CRPC, and PCSM among Caucasian men. No significant associations were found in African-Americans.

The findings of the race-stratified analysis were similar after adjusting for pathologic characteristics, although the associations in the Caucasian subgroup were no longer statistically significant, first author Emma H. Allott, PhD, told Urology Times.

Next: Research will examine possible mechanismsResearch will examine possible mechanisms

“For now, the results of our study are hypothesis-generating and suggest further research is warranted to investigate effects of statins in men with prostate cancer, as well as potential racial differences in these effects,” said Dr. Allott, lecturer in cancer epidemiology at Queen’s University Belfast, Northern Ireland.

“We are in the process of updating our database so that our study may have more power, and then we will see if the suggested associations between statin use and outcomes in white men remain significant in the multivariable adjusted analysis. Going forward, we are also trying to understand the mechanisms that might underlie racial differences in the effects of statins in men with prostate cancer,” added Dr. Allott, previously assistant professor of nutrition, University of North Carolina, Chapel Hill and John Fitzpatrick Research Fellow, Trinity College Dublin.

The research was conducted using the Veterans Affairs hospitals’ Shared Equal Access Regional Cancer Hospital (SEARCH) database, headed by Stephen Freedland, MD, of Cedars-Sinai Medical Center, Los Angeles. The analysis of the impact of pre-ADT statin use on prostate cancer outcomes included 570 men, of whom 42% were African-American and 54% were pre-ADT statin users.

Compared with the non-statin users, statin users were older, had a higher body mass index, and had a shorter median follow-up. There were no significant differences between the statin users and non-users in racial distribution, pathologic findings at radical prostatectomy, or pre-ADT PSA levels.

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The idea that statin use can have a positive effect on prostate cancer outcomes considers their activity for inhibiting production of cholesterol.

“Cholesterol is the precursor for synthesis of sex hormones that may sustain androgen-dependent tumor growth, even in men who achieve castrate serum levels while on ADT,” Dr. Allott said.

She proposed that race-related genetic and genomic differences in tumor biology might account for potential race-related differences in effects of statin use on prostate cancer outcomes.

“There has been little research investigating which molecular subtypes of prostate cancer might be more sensitive to statins. Going forward, we are incorporating molecular tumor profiling in our studies as we try to tease apart the mechanisms,” she said.

Alternatively, the differences observed in Caucasian and African-American men may be non-biologic and related to unmeasured or unadjusted variables.

“For example, there could be differences in comorbidities between the racial groups that are influencing outcomes. By updating our database, we hope that we can adjust for more potential confounders,” Dr. Allott said.