Statins and prostate cancer

[Rob1053]

I have been reading a study from 2011 indicating that use of statin drugs may have a positive effect on reducing the progression of prostate cancer. Is anyone aware of other studies or more recent ones which indicate a slowing of progression or reduction in metastasis? I am considering the implementation of their use if there is a chance in slowing progression. Thanks

[Hidden]

If you click on my name you will see that I asked the same question several days ago in one of my postings. It was answered by the groups renowned expert.

[Rob1053 in reply to Hidden]

Thank you for the information. Looks like it might help, but in higher doses!

[pjoshea13]

I wrote a review of the literature a year ago:

"Non-PCa Prescription Drugs: Statins" (paste into "Search ..." - top-right)

But I see over 40 PubMed hits for <prostate statin 2017>. So, what's new?

At this late stage, considering the data we already have, I'm not so interested in cell & mice studies.

[1] Mayo Clinic.

Thi study looked at "Three hundred and eighty one patients treated {with radiation therapy} between the years of 2000-2005 and 2009-2012", retrospectively.

"... the PSA level at presentation was 20% lower for statin users ... and 33% lower for metformin users ..."

"We did not observe statistically significant associations between the use of statins or metformin and cancer stage"

The first thing to mention is that with such reductions, a significant number of users of these drugs must escape or defer the ordeal of biopsy & treatment. There is detection bias, yet the user & non-user populations didn't differ by stage.

Taken at face value, it seems that statins & Metformin take some of the heat out of the disease. For statins, I'm surprised that the benefit shows up so early.

[2] Italy. "Statins Protect Against Acute RT-related Rectal Toxicity".

I wish I knew that 13 years ago!

"A total of 195 patients received 74.25 Gy in 33 fractions to the prostate and, if involved, to the seminal vescicles (SV). When the risk of SV involvement was >15% according to the Roach's formula, they received 62 Gy in 33 fractions. Overall, 107/195 patients (54.87%) received hormonal therapy (luteinizing hormone-releasing hormone analogue, anti-androgen, or both)."

"In patients with prostate cancer treated with a moderate hypofractionated IMRT schedule, use of statins lowered the incidence and grade of acute rectal toxicity."

Although statins primarily inhibit cholesterol production, it is often forgotten/ignored in cardiovascular studies that they also reduce inflammation.

[3] Germany. Cholesterol / Statins / PCa aggressiveness.

"... we evaluated an association between hypercholesterolemia (≥5.0mmol/l), the use of statins, and advanced/aggressive PC in 767 men with histologically confirmed, clinically localized PC awaiting radical prostatectomy."

"... preoperative hypercholesterolemia is associated with a diagnosis of high-risk PC which is negatively influenced by statin intake."

[4] Steve Freedland. More on inflammation.

"Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties."

"We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial."

"Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had {21%} reduced presence of acute inflammation ... and were {34% }less likely to have severe acute inflammation ..."

"Statin users had {19%} reduced presence of chronic inflammation ... and were {20% & 27%} less likely to have severe chronic ... and severe acute inflammation .., relative to non-users."

"Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk"

IMO, lowering inflammation will take the heat out of the disease.

One can view inflammation as an artifact of PCa, and thus unavoidable, or one can view it as an independent problem. Inhibiting NF-kB (nuclear factor-kappaB) will inhibit inflammation. (A fistful of polyphenols may achieve that without side-effects or too much expense.)

[5] Finland

"The cohort of consisted of 6537 prostate cancer cases diagnosed in the Finnish Randomized Study of Screening for Prostate Cancer population during 1996-2012."

"During the median follow-up of 7.5 yr postdiagnosis 617 men died of prostate cancer. Statin use after diagnosis was associated with a {20%} decreased risk of prostate cancer death ..."

"The risk decrease was clearest in men managed with androgen deprivation therapy."

Which is what I would expect, since access to cholesterol for steroidogenesis becomes critical while on ADT.

[6] Denmark

"Among 31,790 patients, 7,365 died of prostate cancer and 11,811 died from other causes during a median follow-up of 2.8 years"

"Postdiagnosis statin use was associated with {17% less risk} for prostate cancer mortality and (19% less risk} for all-cause mortality."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[2] ncbi.nlm.nih.gov/pubmed/283...

[3] ncbi.nlm.nih.gov/pmc/articl...

[4] ncbi.nlm.nih.gov/pubmed/284...

[5] ncbi.nlm.nih.gov/pubmed/287...

[6] ncbi.nlm.nih.gov/pubmed/288...

[Rob1053 in reply to pjoshea13]

Thank you, very informative. Think it is worth a try for the risk. I saw some literature suggesting small doses might exacerbate the Pca, but higher doses looks promising. Not sure on doses appropriate, but will discuss with dr. Thanks again!

[pjoshea13 in reply to Rob1053]

Rob,

The literature suggests that a higher dose is always better.

When I asked my GP for high-dose Simvastatin 6 years ago, he told me that my timing was off. The maximum dose had just been withdrawn for new patients. Those already on 80mg were grandfathered! I had to make do with 40mg. Crazy that the company didn't introduce a 60mg dose, say.

I understand that 80mg is still available in some countries.

-Patrick

[Rob1053 in reply to pjoshea13]

Thank you Patrick!!

I think I will try Lipitor (Atorvastatin) to see if I can tolerate. am 64 and have a cholesterol a little high, but not bad.

[Hazard]

I had a chat to the Head of Urology at Peter MacCallum before christmas and he mentioned both metformin and statins as potentially iseful agents. But since then I have started chemo and MO has not raised this at all. I really need to follow up with him regarding this.