A recent article in the Journal of Clinical Oncology, together with an associated editorial, have addressed the issue of whether evidence is now sufficient to argue that all men with prostate cancer should be treated with a statin.
The article by Larsen et al. provides an analysis, based on data in the Danish health data registries, of all men in Denmark diagnosed with adenocarcinoma of the prostate between 1998 and 2011, together with related data on tumor and patient characteristics, drug use, and primary treatment for these men. We reported on this study when it was first published on line in August.
Larsen et al. concluded that:
Postdiagnosis statin use was associated with reduced mortality from prostate cancer; however, it remains to be established whether this association is causal.
However, one does have to say that the median follow-up of these 31,500+ patients out in the “real world” was relatively short.
The associated editorial by Mucci and Kantoff is new, however, and asks bluntly, “Is the evidence sufficient to recommend statins for all men with prostate cancer?”
The full text of this editorial is available on line and so we would encourage the interested reader to peruse it for him- or herself.
However, despite the fact that
Epidemiologic studies are quite consistent with regard to a beneficial role of statin use after diagnosis across the continuum of prostate cancer
Mucci and Kantoff conclude that we are not yet ready to recommend statins for all men with prostate cancer.
On the other hand, what they do state we are ready for is at least one and maybe two or more randomized, prospective clinical trials:
- The one they recommend would be in men with high-risk, non-metastatic prostate cancer (e.g., M0 patients with a high PSA doubling time) who could be randomly assigned to treatment with ADT with or without a statin. The primary end point for this study would be metastasis-free survival, and ideally, a racially diverse population would be recruited (because of the marked disparities in prostate cancer mortality in African-American men and the potentially lower prevalence of statin use in such men).
- The other one that they imply would be interesting would be in men starting on active surveillance, who would be randomized (presumably) to either a statin or a placebo, although it might be difficult to define a really workable primary endpoint for such a trial (because a lot of men still come off active surveillance due to “cancer anxiety” as opposed to any categorical clinical factor).
Clearly, other, analogous trials would be possible, but time to disease progression might mean that patients would need to be followed for at least 10 years before any conclusions could be drawn from such trials. This means that the costs associated with implementation of such trials would be considerable.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: mortality, progression, risk, statin, Treatment |
THE "NEW" PROSTATE CANCER INFOLINK 
Isn’t it a bit like chicken soup? “Can’t hurt…”
Since statins, I believe, don’t seem to have bad SEs and do have cardiovascular benefits and apparently prostate cancer benefits, why not have high-risk patients take them?
Bob
Dear Bob and Unreasonable Man:
I think we need to distinguish between what clinicians are currently doing (which is quite often to have their patients on a statin) and proof that such a strategy is both safe and effective.
Statins do have side effects. For example, those commonly associated with atorvastatin (Lipitor) — a generically available and commonly used statin — include nasopharyngitis, arthralgia, diarrhea, pain in extremity, urinary tract infection, and others (click here for the details)
Well:
(1) The data, including those you supply, show that atorvastatin (as an example) is safe and well-tolerated and that a large number of the adverse reactions are psychosomatic.
(2) In case they are not, they are voluntary and reversible, in contrast to those of prostate cancer (ignoring the “voluntary” element of treatment choice, “losing” at AS, etc.) So there is a substantial population, in which I am included, who get any benefit for free, since the long-term safety of statins is well documented.
(3) But they are powerful medicine. In fact I take a statin only because I had high PSA: various doctors had been pressing me for years. I was reluctant to tinker so deep in my biochemistry. And I would still rather not. I realise controversy surrounds the whole area and that the survival benefit for cardiovascular causes might not be that large. I think we prostate cancer patients have different odds though. I admit the data on pure statin use in prostate cancer are blurry. But they seem to be in the direction of helping. So, if well tolerated, as mine are, I think the risk/reward is favourable.
Disclaimer: I also take metformin, looking for indicated but not proven synergistic effects. I realise this is a long way from becoming standard of care, but it is my judgment in my case.
Dear Unreasonable Man:
The well-informed patient who is able to make a sophisticated assessment of his (or indeed her) risk/benefit ratio is always in a very different position to the “average patient in the street” (who often wants someone to tell him/her “what to do”).
As with playing games like poker for money, there is always risk involved and the question is always “how much risk?” The sophisticated poker player can intelligently take risks that I would never take (but then I used to play bridge for money; poker never appealed to me).
OK, to try to live up to my handle as well as you are: THERE IS NO RISK.
So: I am your urologist (or whoever) and I have just told you you have prostate cancer. You are the “uninformed” patient. No-one in this transaction needs to be a professional gambler, least of all with their life or heaven forbid anyone else’s.
“You have prostate cancer. Take a Statin”.
2 weeks pass
“How are you? Have you looked at all those leaflets?”
2 cases
(1) “Oh Doc; I feel like my limbs are in a vice; my nose is streaming; I can’t add 2 + 2 ….”
“Ooh; best stop the statin”
(2) “Fine” (with 98% probability)
I think there is a broader issue here, which is that the doctor’s objectives do not always coincide with the best interest of the patient. If there is a medication that is inexpensive, is unlikely to have serious or irreversible side effects, and for which observational studies have shown apparent anti-cancer benefit, it seems to me reasonable to offer that drug as an option to any cancer patient. A reasonable person would conclude that the downside risk is pretty small, and there may just be a benefit, and in the face of a lethal disease such a risk is worth taking.
Many — perhaps most — doctors do not see things that way. They are very reluctant to depart from the “standard of care” because of fear of litigation, fear of disapproval of colleagues, the need to adhere to institutional norms, or doubt of their own ability to assess risk. Doctors will use excuses such as claiming to practice “evidence-based medicine”, but if they really wanted to give the patient his best shot they would be more willing to take a calculated risk.
Having said that, I do not claim to be an expert on the adverse effects of statins. They are certainly very widely used and are generally very safe, but whether there are some very infrequent side effects that are so severe as to tilt the balance of risk, I cannot say.
Dear Tom:
(1) Most specialists who treat prostate cancer have little to no experience of managing men on statins (which are usually prescribed by primary care physicians and cardiologists).
(2) There are indeed “some very infrequent side effects that are so severe” as to potentially tilt the balance of risk (click here for example) in many people.
(3) Most patients have not done anything even close to the sort of homework that you have done and never read the warnings and adverse events sections of the prescribing information for the drugs that are prescribed for them.
(4) I am personally delighted that most physicians are “reluctant to depart from the ‘standard of care'”. Being a physician today is extremely difficult. I don’t have to waste any time actually treating patients and yet I have a hard time keeping up with the literature in just one single disorder! It is become almost impossible for most physicians to do so.
(5) If you worked in a profession where a subset of your customers (with the industrious backing of their lawyers) was ready to try to put you out of business by filing law suits at the drop of a hat, you might also appreciate why physicians today are rather cautious about the use of unproven medical care.
I have no problem with a physician and his or her patient discussing the use of statins as an option in the management of prostate cancer and reaching a shared decision. That is not the same as offering a statin to “any cancer patient”. We have no evidence that that would be wise at all.