Statins and risk for diagnosis of prostate cancer … a not so small surprise

A recently published article in Prostate Cancer and Prostatic Diseases has suggested (again) that statin therapy can decrease risk for a diagnosis of prostate cancer … but this new article comes with a special twist in the tail ….

The full text of the article by Lustman et al. appears on the Medscape Oncology web site (which you need to join to see) or the abstract is also available on line.

Lustman et al. used the Clalit Health Services database to look at the association between statin therapy and risk for diagnosis of prostate cancer among a total of 66,741 eligible participants enrolled in the Clalit Health system in Israel. Patients were all initially identified as of January, 2001 and followed for a total of 9 years through to December 31, 2009.

Clalit Health Services is Israel’s largest health maintenance organizations, managing health services for some 54 percent of the Israeli population. All study participants had similar health insurance and similar access to health services. Computerized personal medical data contains the members’ demographic, clinical, laboratory and medication data. Prescription records are available since 1998, and include brand and dose of medicine as well as the number of prescriptions filled per patient per year. The actual study population included all male individuals between 45 and 85 years of age enrolled with the Central Region of Clalit Health Services during the study period specified above. Men with a diagnosis of prostate cancer or a diagnosis of an undefined malignancy with a PSA level > 6.5 ng/ml prior 1 January 2001 and subjects with incomplete follow-up were excluded.

Here is a summary of the key study findings:

  • The average (mean) age of participants at cohort entry was 58 years.
  • 11,245 subjects (16.8 percent) died during the 9-year follow-up period.
  • 37,645 subjects (56 percent) filled at least one prescription for a statin during the study period.
  • 26,061 subjects (39 percent) filled prescriptions for statins for at least 12 months during the study period.
  • Subjects treated with statins were
    • Older
    • More likely to be new immigrants to Israel
    • More likely to be of lower socioeconomic status
    • More likely to be smokers
    • More likely to have diagnoses of diabetes mellitus and cardiovascular disease
  • Compared to risk for prostate cancer among men who had not used a statin prior to diagnosis
    • The risk of diagnosis with incident prostate cancer was lower (hazard ratio [HR] = 0.72) among all statin users (even when statin use was for < 12 months).
    • The risk for diagnosis was even lower (HR = 0.26) among those who had used a statin use for > 5 years.
    • The risk for diagnosis with incident prostate cancer appears to decrease with cumulative increases in statin use.
    • A cumulative dose of < 5,000 mg of a statin appears to reduce risk for diagnosis of  incident prostate cancer (HR = 0.82).
    • This reduction in risk was highest among men with a cumulative dose over 20,001 mg (HR =  0.26).
  • Reduction in risk for a diagnosis of incident prostate cancer appeared to be statin specific.
  • Among subjects who used statins for 6 months or longer
    • Simvastatin (Mevacor) reduced risk for a diagnosis of prostate cancer with an HR = 0.51.
    • Atorvastatin (Lipitor) reduced risk for a diagnosis of prostate cancer with an HR = 0.48.
    • Rosuvastatin (Crestor) reduced risk for a diagnosis of prostate cancer with an HR = 0.22.
    • Treatment with fluvastatin, lovastatin, and pravastatin was not associated with any significant reduction in risk for diagnosis of incident prostate cancer.
    • Hydrophilic statins as a group showed no association with incident prostate cancer.
    • Hydrophobic statins as a group reduced the risk for a diagnosis of incident prostate cancer with an HR = 0.48.

It has to be said that this is a somewhat unexpected set of findings (and your sitemaster notes, in the spirit of full disclosure, that he has been treated with rosuvastatin for nearly all of the past 5 years).

Lustman et al. conclude, based on their data, that,

the use of statins reduces the risk of prostate cancer in a dose-related and time-dependent manner, although this appears not to be equally true for all types of statins.

However, they also note that:

It would appear that the mechanism of action in reducing cancer-cell proliferation and apoptosis is not only dependent on the statins’ ability to reduce cholesterol, as this would cause a fairly uniform reduction in cancer incidence independent of the statin type. It appears likely that a number of mechanisms are working simultaneously and that not all types of statin trigger these different mechanisms.

It is clear that these data need to be confirmed by data drawn from other, similar, large data sets before any serious conclusions can be drawn. However, in the interim — since he has to take a statin for reasons that have nothing to do with prostate cancer — your sitemaster will be continuing to take his rosuvastatin, and he will be bringing these data to the attention of his own primary care clinician.

9 Responses

  1. Going to keep taking mine too. ;-)

  2. It should also be noted that Crestor has the highest potential side-effect profile compared to the other statins. In addition, Dr. Meyers mentioned on his blog a few weeks ago that some of this may be due to the CYP pathway that Crestor uses versus the others and that that may be why it has a constructive effect on prostate cancer progression.

  3. Would someone taking a statin need to adjust his PSA, for purposes of a biopsy threshold, the way someone taking a 5-ARI should?

  4. Dear Jonathon:

    I am not aware that taking a statin has any direct effect on patients’ PSA levels. Taking a 5-ARI like dutasteride definitely does affect PSA levels because 5-ARIs also have the effect of shrinking the prostate.

  5. Dear John L.:

    The current paper does not address the question of whether a man should take statin therapy exclusively to limit risk of prostate cancer. It merely points out that those men who were taking statin therapy for some other reason appear to have reduced risk for diagnosis of prostate cancer (especially if they were using a hydrophobic statin).

    The question of whether specific statins could or should be used to prevent prostate cancer in men with no other reason to be treated with one of those statins would need to be tested in a randomized, double-blind clinical trial to assess the relative benefit/risk equation. This might, for example, be a potential strategy for men at high familial or ethnic risk for prostate cancer, but not for those at normal or low levels of familial or ethnic risk.

  6. After I typed my question about statins lowering PSA levels, I came across this article which (in the full text) cites some authorities suggesting that statins tend to lower PSA levels. That would be one concern about taking a statin to reduce the risk of prostate cancer. It could lull one into a false sense of security. (“My PSA is down, and is below a traditional biopsy threshold, so I don’t need a biopsy”.) Then fewer biopsies would result in fewer detected prostate cancers. (Sort of like 5-ARI, if one failed to adjust for the psa-lowering impact.)

  7. Jonathon:

    This has indeed been suggested. However, I am not aware of any significant study that has actually confirmed this suggestion.

  8. Hi. I have Gleason 9, PSA rose from 4 to 24 in 18 months, one lymph node affected, and suspected bone mets to left hip. Started hormone therapy on diagnosis 1 month ago, and due to start radiotherapy in c. 2 months. I have been taking 10 mg of atorvastatin for just over 12 months, after c. 10 years on rosuvastatin. I felt well below par since the switch, and had wondered whether it was that change that allowed my immune system to drop. Any views on different types of statin, and ideal protective dosage?

  9. Dear David:

    Rosuvastatin (Crestor) is a “stronger” statin than atorvastatin (Lipitor). However, I am not aware that it would necessarily have a greater effect (if any) on the efficiency of one’s immune system. Statins are not, after all, primarily designed to impact the efficiency of the immune system and I am not aware of any comparative data on different statins with regard to such activity.

    On the other hand, it is a little unclear to me why anyone would switch you from rosuvastatin to atorvastatin after 10 years on the former drug, and so maybe the simplest issue is to ask your doctor to switch you back to the rosuvastatin. It may or may not make a blind bit of difference with regard to any effect on your immune system, but it may affect how well your cardiovascular system is functioning.

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