Do Statins Prevent Lethal Prostate Cancer?

Statins are toying with prostate cancer scientists.

Study after study hints at a tantalizing connection between taking these cholesterol-lowering drugs and protection from getting lethal prostate cancer.

But an actual magic pill guaranteed to do this just keeps hovering just over the horizon, like the Goodyear Blimp, taunting scientists and oncologists who would love to have something to give to men and say, “Here, take this every day, and you won’t get aggressive prostate cancer.” Or, “This will lower your chances of having your prostate cancer come back after treatment.” Or. “This will help you stay on active surveillance and not develop a higher grade of cancer that needs treatment.”

The link between statins and all these scenarios hasn’t been definitively proven yet. On the other hand, it won’t go away, either.

The problem is, there’s a big difference between suspecting that statins might have a protective effect against aggressive prostate cancer and being willing to go out on a limb and recommend that all men start taking them.

So far, not a single scientist is prepared to do that.

And still, statins won’t go away. What is it about these drugs, anyway? Is it the fact that statins lower cholesterol, and that this in itself somehow changes the body’s susceptibility to prostate cancer? Or is it some other biochemical action of these drugs?

Nobody’s entirely sure about that, either. Meanwhile, here statins sit, blowing raspberries and waggling their ears at scientists trying to find the answers.

The latest study to tease prostate cancer scientists comes from Denmark: scientists looked at nationwide Danish registries and identified 31,790 men who were diagnosed with prostate cancer from 1998 to 2011; of these, 7,365 died of the disease.   (Note: the study does not describe how these men were treated, nor whether they were diagnosed by regular screening. Also, there are more and better treatments for prostate cancer now than there were back then – so don’t get distracted by these numbers; that’s not the point of this article.) Then they looked to see which of these men had also taken statin drugs, and how these men fared compared to the men who had not taken them. In secondary analyses, they looked at the use of statins before prostate cancer diagnosis, and at one year or five years after diagnosis. They concluded that men who took statins after diagnosis were less likely to die from prostate cancer. “However,” the scientists reported, “it remains to be established whether this association is causal.”

Yeah.  In an accompanying editorial in the Journal of Clinical Oncology, Harvard epidemiologist Lorelei Mucci, Sc.D., M.P.H., and Memorial Sloan Kettering oncologist Philip Kantoff, M.D., note that “cholesterol is a precursor of androgens (male hormones) and…can act by reducing androgen bioavailability, thereby limiting tumor growth.” In other words, cholesterol feeds androgens, which in turn, feed a prostate tumor.

Statins act on this pathway, but they also act in some other, cholesterol-independent ways that affect prostate tumors. “Given the multiplicity of possible mechanisms by which statins might work,” the editorial said, “it would be of clinical interest to know whether nonstatin lipid-lowering drugs have the same effect as statins on prostate cancer mortality.

“Taken together, the data from (this and other statin studies) point toward a substantial salutary effect associated with statins, with hazard ratios (a way to measure the effect of a treatment) comparable to many of the more toxic and more expensive agents that now are used for advanced prostate cancer.” And now here comes the uncertainty: With studies like this, the editorial continues, “there is a risk that systematic error… may explain the observed associations.” In other words, are there complicating factors that could be messing up how these results are viewed?

Almost certainly there are, says Johns Hopkins epidemiologist Elizabeth Platz, Sc.D., M.P.H. “You can’t rule out bias in these studies. Even though the investigators tried to take other factors into account, when you look at the patients who were taking a statin and those who were not, they’re very different people. So I worry about saying to all men, ‘Take a statin just because you have prostate cancer and want to be able to do something.’”

That said, “I think there actually is something in statins that protects against prostate cancer. But until we can rule out confounding factors, I can’t say that men should take a statin even if they don’t have a cardiovascular need.”

On the other hand, she adds, if you’re already taking a statin because a doctor has put you on one to help prevent a heart attack or stroke, you may also get some bonus protection against lethal prostate cancer.

Why shouldn’t you just start taking a statin? Because these drugs can have complications, including inflammatory arthritis, muscle weakness, and inflammation of the colon. “If you take a huge group of men who don’t have prostate cancer,” says Platz, “or men who have survived prostate cancer but who have a risk of it coming back, you certainly would not want to tell them to take a statin to prevent lethal prostate cancer, because you would cause a ton of side effects.”

Just about every drug has side effects – even aspirin, which many people take as a preventive measure against stroke, heart disease, and colon cancer. But aspirin also raises the risk of gastrointestinal bleeding, among other things. So there’s a balance: is it better to run a slight risk of a GI bleed and lower your risk of having a stroke?

“Everyone wants to do a trial to prove that statins work,” says Platz. But that’s a lot easier said than done. “So many men are already taking a statin. It wouldn’t be ethical to take them off of that medicine to get them into a trial. We also need more basic science to understand the mechanisms of statins, and the mechanisms of the side effects, too.” At some point, she believes, someone will do a big clinical trial that will answer the question of statins as adjuvant therapy or prevention for prostate cancer once and for all – but it’s going to be really hard. “You might have two guys who look just the same, but one will have a different inflammatory milieu than the other; one will be more pre-diabetic.”

Here’s the kicker: No drug, ever, has proven to be as effective at protecting against prostate cancer and pre-mature death in general as having a healthy weight and being physically active. “If you want to reduce your risk of lethal prostate cancer while increasing your well-being, improve your diet and increase your activity level. Improving your diet is good for reducing your heart attack risk, too. It’s good for your overall health. “

Men who have diabetes are not more likely to get prostate cancer, but they are more likely to die of it if they do get it, “probably due to some very complex pathways that may have to do with glucose itself, or insulin, or the inflammatory environment that seems to result in diabetes,” continues Platz. “So another important thing for men to think about, if they are at risk, pre-diabetic, or diabetic, is to get their blood sugar under control, improve their diet, and exercise to put on lean mass,” and get rid of excess body fat.

There are no shortcuts here. There is no magic bullet. And in Platz’s opinion, shortcuts may not be the way to go, anyway. “If you take a pill, you’re messing with the system. There are going to be side effects, and it’s not holistic. Changing your diet and lifestyle will benefit many aspects of your health, including your mental wellbeing. You’ll feel better if you lose weight and exercise.”

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington