Statins and prostate cancer

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The use of statins to control dyslipidemia is now over 20 years old and supported for patients with coronary artery disease by the landmark Scandanavian Simvastatin Survival Study published in 1994. That study demonstrated a significant reduction in the rate of myocardial infarction and death among treated patients and remarkable safety. Subsequently numerous trials demonstrated their efficacy and safety in the cardiovascular arena even among patients with relatively normal lipid profiles and found a wide variety of other “off target” effects of statins which were originally designed to inhibit HMG-CoA reductase, a key enzyme in the regulation of cholesterol. For example the JUPITER trial highlighted the importance of CRP, a marker of inflammation as a possible additional mechanism of action.

Fortunately, many of the “off target effects” of the statins also have the ability to suppress cancer development, some of which may relate to the evolving understanding of insulin resistance and insulin as a growth factor for prostate cancer. Dozens of articles have been published on the efficacy of statins to reduce the incidence of a wider variety of cancers, including (but not limited to) colon, breast, esophageal, gastric, and melanoma because their use is so common in the population and both cancer and heart disease are common to the aging process. The studies are often confounded by “what else” patients might have been doing (exercise, low fat diets, taking NSAIDS, finasteride, dutasteride, etc), but in general it is likely that statin use is beneficial in prevention and perhaps in prolongation of survival among patients with prostate cancer. In one of the larger articles demonstrating this effect, Yu et. al. studied 11,772 men from the UK who were newly diagnosed with non-metastatic prostate cancer between 1998 and 2009. They published these conclusions in the Journal of Clinical Oncology last year:

“During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively).”

A very balanced editorial accompanied this publication reviewing the many similar articles and came to the cautious conclusion that “the current data may be sufficient to sway some clinical decisions toward statin use for men who are on the borderline for cardiovascular disease prevention.” I would certainly concur with this opinion, and if you have family members at risk for prostate cancer, it would seem prudent for them to have their lipid profiles tested and (given the other potential benefits and low risks for statin use) have them discuss starting statins if they have not already done so. Adding statin “therapy” after prostate cancer is diagnosed is probably of little harm, but as with metformin, much less proven as an interventional strategy.

8 Comments

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8 responses to “Statins and prostate cancer

  1. tarhoosier

    But what about after treatment, with psa of <0.015 and high risk of recurrence? I am currently in this category and using metformin and atorvastatin with appropriate testing to monitor. Is this wise?
    (Also dutasteride and supplements per C. Myers.)

  2. I am unable to give personal advice on therapy in this blog. The details of every man’s case are important and should be discussed directly with their physician. I hope you can understand.

  3. David Stevens

    Dr. Glode – – I’ll discuss my personal situation with you next time we meet but I was wondering what your thoughts are, generally, on the appropriate dose of statins for PCa combat. I take a 20mg dose of Crestor which keeps my LDL really, really low. But for PCa, I just don’t know if that’s enough.

  4. David Lacey

    Dr. Glode, thanks, and very interesting. If I were borderline cardiovascular disease I would choose a plant whole-food low-fat diet before I would submit to statins and all their side effects. Caldwell Esselstyn, MD, has published a new study of his patients showing successful heart disease reversal with diet. There is also evidence that this diet (life style) has can be be helpful in slowing or preventing prostate cancer, especially it’s non-dairy and low fat aspects. Kaiser Permanente has recently published a booklet on plant based diets (last link) which is interesting in that the conversation around heart disease and cancer seems more inclusive now to diet alternatives. https://mail.google.com/mail/u/0/?tab=cm#label/HLTH-NUTRITION%2FGREGER+McDOUG+VIDEOS/1472cb7bb46e9254

    Regards and, again, thanks for your excellent blog.
    David

  5. drjacobschor

    While the citations you link to provide a strong argument for prostate cancer patients to take statins, or perhaps more importantly to have been taking statins prior to diagnosis, it is worth recalling how the initial excitement about statins and breast cancer has suddenly faded.

    In April 2013, Teemu Murtola reported that statin use was associated with a 66% reduction in the risk of dying from breast cancer. Murtola’s had looked at statin use and breast cancer mortality among the 31,114 women with breast cancer who were diagnosed in Finland between 1995-2003. During follow up 6,011 of the women died, 3,169 due to breast cancer. The death rate among statin users was 7.5% while among non-statin users it was 21%. Women with localized disease who took statins were 67% less likely to die than nonusers (hazard ratio, 0.33). Among those with metastatic disease, statins use was associated with a 48% decreased risk of death.

    Similar but less dramatic decreases in breast cancer occurrence had been reported by Cauley in 2006. Non-significant trends toward lower breast cancer risk were seen in the statin takers. Breast cancer incidence was 4.09 per 1000 person-years among statin users and 4.28 per 1000 among nonusers. Hydrophobic statins (i.e., simvastatin, lovastatin, and fluvastatin) were used by 8,106 women, and use was associated with a significant 18% lower breast cancer incidence. Use of other statins (i.e., pravastatin and atorvastatin) or nonstatin lipid-lowering agents was not associated with breast cancer incidence.

    These reports and others generated considerable excitement but follow up studies failed to confirm initial benefits.

    A meta-analysis by (Undela 2012) found no significant benefit. “A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis… Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99 and RR = 1.03).”

    Another meta-analysis (Emberson 2012), which analyzed data drawn from 22 randomized, controlled trials with 66,582 patients receiving statins and 66,604 placebos, reported that five years of statin therapy had no effect on the risk of cancer-related death (RR 1.00).

    A March 2014 editorial sums up the current situation: “As of today, the accumulated epidemiological evidence does not support the hypothesis that statin use affects the risk of developing breast cancer when taken at low doses for managing hypercholesterolemia.
    While the paper by Oriana Yu you mention in your blog reported striking results, we shouldn’t forget Chao’s 2013 paper that reported ‘Neither preoperative nor postoperative statin use was associated with biochemical recurrence (hazard ratio [HR] = 1.00 [0.72-1.39] and 1.05 [0.76-1.46], respectively) or clinical disease progression (HR = 0.63 [0.31-1.27] and 1.20 [0.63-2.30], respectively). No clear dose-response relationship was found for duration of use.’

    Cancer biology has a habit of being more complicated than we want it to be and the seemingly beneficial associations that seem so significant in one trial, seem to evaporate in another. As much as we would like to base decisions on fact, often we are making educated guesses, heeding information from a handful of studies while ignoring the results from others.

    It may be that the type of statin taken makes a difference (hydrophilic vs. hydrophobic) or whether a specific tumor has HMG CoA receptors or not, at least in breast cancer.

    There is good logic to promote statins for cardiovascular disease prevention and perhaps for prostate cancer. Just don’t be surprised if a year from now scientific opinion has done an about face.

    • This is an EXCELLENT post and I very much appreciate the balance it provides, to say nothing of the expanded references on studies. On the one hand , statin use has clear efficacy in cardiovascular disease, but on the other, details as regards interaction with neoplasia are indeed likely to be complex. I suppose the good news about statins is that 30 years on, they don’t seem to CAUSE cancer or any other significant problems for the most part other than myositis. They are almost as good as fluorides in terms of candidacy to add to the water supply! The yin/yang studies you mention are of course reminiscent of the ever changing population studies on alcohol and caffeine consumption. We will probably never arrive at a clear picture. But to close with a non-sequitur, smoking DOES cause cancer for what that’s worth.

  6. Pingback: A statin a day?? | prost8blog

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