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Conversations With Prostate Cancer Experts


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Statins, Cholesterol + Prostate Cancer

Dr. Lorelei Mucci specializes in prostate cancer epidemiology and her research focuses on cancer risk and mortality in populations across the globe.

Prostatepedia spoke with her about cholesterol, statins and prostate cancer.

Join Prostatepedia to read the rest of Dr. Mucci’s comments.

What is the role of cholesterol in prostate cancer? And statins?

Dr. Mucci: This is a very interesting and important area of research. There have been a number of well conducted epidemiological studies showing that high cholesterol levels are associated with a higher risk of more aggressive prostate cancer.

Cholesterol synthesis and biosynthesis pathways seem to be altered in men with more aggressive forms of prostate cancer. Cholesterol can be used to synthesize androgens; they’re the backbone for androgen synthesis.

The epidemiological evidence for the association between statins and the decreased risk of advanced prostate cancer is quite good. The question is: Is this a true association? Is the mechanism specifically through cholesterol-lowering? There seems to be some evidence that the lowered risk of aggressive prostate cancer may act through regulating cholesterol levels, but some of statins’ effects on aggressive prostate cancer may be independent of cholesterol.

I do think the data are fairly strong around statins. Again, whether that is totally through cholesterol-lowering or other specific pathways is not clear. (See http://ascopubs.org/doi/ pdf/10.1200/JCO.2017.74.7915 to read more of Dr. Mucci’s thoughts on statins and prostate cancer.)

Do statins impact the effectiveness of drugs like Zytiga (abiraterone)?

Dr. Mucci: I am a co-author on a study looking at the effect of statins on androgen deprivation therapy. One of the pathways that statins use to get into prostate cells is the same set of pathways that androgens use.

One thought is that statins may help these other antiandrogen medications by blocking the cellular pathways androgens use. There is both interesting human and experimental data suggesting that statins may benefit these antiandrogen therapies.

This is a very interesting area of research. It might be early on in terms of evidence, but I do think it will be really important to look at how things like statins—and potentially other things like aspirin—are associated with a lower risk of aggressive prostate cancer. It may be really important to think about the possible impact on treatment that other medications that men may be taking at the same time as medications for prostate cancer could have. We may be able to repurpose drugs we hadn’t really thought about before for prostate cancer either on their own or in combination with other therapies.

Should we prescribe statins for all men with prostate cancer? I don’t know that the evidence is good enough for us to recommend that, but we do feel that statins are probably very safe for men who have prostate cancer. If a man with prostate cancer has high cholesterol levels and a high heart disease risk, I think going on a statin is safe. I think it’s premature to suggest that we put all men on statins, though.

Do we have long-term data on statin use from the cardiovascular community?

Dr. Mucci: Looking at secondary outcomes like prostate cancer?

Yes.

Dr. Mucci: That’s a great question. A lot of the cardiovascular studies have been small, but if there’s enough follow-up, and if you pool all the studies together, that may be enough. I would be surprised if someone hasn’t started looking at that.

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Clinical Trial: Statins Before Surgery

Dr. Hyung Kim is a urologic oncologist at Cedars-Sinai in Los Angeles.

Prostatepedia spoke with him recently about a clinical trial he’s running that looks at the effects of cholesterol-lowering therapy before radical prostatectomy.

What do we know currently about the connection between cholesterol, statins, and prostate cancer?

Dr. Kim: A lot of our data comes from epidemiology studies in which statins were used to lower cholesterol to improve cardiovascular health. In many of these studies, the observation was made that patients with prostate cancer who were on statins were less likely to die of their cancers

The other line of evidence comes from basic science research. People like Dr. Michael Freeman have done preclinical laboratory studies showing that lowering cholesterol levels in mice can slow down the growth of prostate cancer.

We have epidemiology data. We have preclinical data. The missing piece is prospective data in patients to help establish a firm cause/effect relationship between lowering cholesterol and favorable prostate cancer outcomes.

The epidemiology data is interesting because the link between statin use and the incidence of prostate cancer is weak, but there is a stronger link between statin use and the likelihood of dying from prostate cancer.

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This suggests the possibility that statin use targets the lethal form of prostate cancer. It also suggests that statin use may not lower the likelihood of developing prostate cancer. However, if you develop prostate cancer, perhaps statin use will improve your likelihood of surviving the disease.

Mouse studies are controlled experiments where you do see a clear cause/effect relationship. You lower the cholesterol level in the mice and the tumors you implant in them grow more slowly. We have some idea of the basic mechanism behind this observation, but does this cause-and-effect relationship carry over to patients? Does that cause/effect relationship explain the epidemiology data that we see?

Those are the unknowns. This is why we’re conducting our trial.

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Download February 2017 Prostatepedia.

Read more about this trial and about the link between cholesterol, statins, and prostate cancer.