Statins in Prostate Cancer and the Relationship in Men Undergoing Active Surveillance

The Fountain of Youth is thought to be a mystical spring that restores youth upon its drinkers. It has been searched for dating back to before the ancient Romans. Many people spent their lives chasing it – just ask Ponce De Leon! We now know the Fountain of Youth does not exist. In more recent times, the Fountain of Youth has been replaced by various remedies such as elixirs, oils, ointments, and herbs. More recently, people have turned to pharmaceuticals, of which statins has been one of the most touted. Statins are currently the most widely prescribed class of medicines. However, unlike various treatments of the past, statins are very effective. Specifically, they acutely block cholesterol production thereby lowering serum cholesterol levels typically by ~25%. In turn, this leads to dramatic reductions in heart disease risk.

Given the presumed importance of cholesterol in cancer pathways (it is the precursor for androgens as well as important in cell signaling pathways), there are multiple reasons to believe statins have anti-prostate cancer properties. While multiple studies have examined the role of statins in prostate cancer, often with mixed results, no prior study has examined this relationship in men undergoing active surveillance.

To address this gap in the literature, Jayalath et al. examined 797 men with low-risk prostate cancer managed by active surveillance at the University of Toronto, one of the world leaders in active surveillance. Unlike most active surveillance cohorts, their cohort data dates back to 1995. With a strict definition of “low-risk” – Gleason <7, ≤3 cores positive, <50% involvement of any core and PSA <10 ng/ml – these men actually had “very low-risk disease” per NCCN criteria. They found that 24% of their cohort used statins at baseline. Overall statin user and non-users were well matched except the statin users were more likely to also use NSAIDs (which may have their own anti-prostate cancer activity) and 5-alpha reductase inhibitors.

At the confirmatory biopsy, which occurred a median of 11 months later, 24% were reclassified to low-risk or higher (Gleason Score ≥7, 67 ≥4 positive cores, or >50% core involvement). There was no significant difference in reclassification rates by statin use, and if anything, statin users had a slightly higher risk of reclassification (24% higher risk, but not significant). Among men who were not reclassified, 25% were later reclassified while 33% progressed by therapy (first of pathological progression, or initiation of definitive treatment without pathologic indication). Looking at progression rates over time, results were similar between statin users and non-users, though in this case statins users had slightly lower progression risks, though again this was not significant. In summary, the results showed no “benefit” to statin use.

In studies such as this, it is important to keep a few things in mind. First, this is not a randomized trial. Men took statins for a reason – typically due to elevated cholesterol or concerns about heart disease risk. Given both of these are linked with more aggressive disease (in some studies), one could argue that a null finding actually suggests statins negated the adverse effects of cholesterol and heart disease. Second, given this is not a randomized trial, statin users and non-users differ in other ways. Statin users went to the doctor, had their cholesterol checked, may have tried lifestyle modifications such as diet and exercise, and only when that did not work, were put on the drug. This preventive and proactive health seeking behavior of statin users means that any “benefits” from statins could simply be attributed to other factors.

What is the take-home message? First – given statins had no “benefits” despite the issues mentioned above, this data actually say statins are more like the elixirs of yesteryear than the new Fountain of Youth – at least for delaying prostate cancer progression in men on active surveillance. However, given the clear known health benefits of statins for cardiovascular disease and the strong preclinical data supporting the role of cholesterol and prostate cancer, I am not yet ready to lump statins in with snake oil. I do think there is something there. However, I do agree with the findings that in an unselected group of men, statins probably have minimal prostate cancer benefits. Future research is needed to understand which tumors are statin sensitive, which are cholesterol sensitive but need stronger cholesterol medicines than statins, and which tumors are truly cholesterol independent. Once we have those answers, then and only then, will the true power of statins (or any other modern drug) emerge.

Written by: Stephen J. Freedland, MD, Warschaw Robertson Law Families Chair in Prostate Cancer, Director, Center for Integrated Research in Cancer and Lifestyle, Co-Director, Cancer Genetics, and Prevention Program Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute, Professor, Surgery at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute.

Read the Full-Text Article: Statin Use and Time to Progression in Men on Active Surveillance for Prostate Cancer
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