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Posted: Sep 04, 2015
Tags: acute renal failure hormonal therapy prostate, cardiovascular disease hormonal therapy, metabolic syndrome prostate cancer, metformin prostate cancer, PSA doubling times prostate, Uncategorized,
In the March 2015 issue of Prostate Forum, we feature conversations with:
Dr. Giorgio Gandaglia of Italy’s Vita-Salute San Raffaele University about hormonal therapy and acute renal failure;
Dr. Stephen Freedland of Cedars-Sinai Medical Center in Los Angeles about PSA doubling times; and
Dr. Neil Fleshner of University of Toronto about metabolic syndrome and hormonal therapy.
Here’s Dr. Myers’s introduction to the issue.
from Prostate Forum March 2015 Volume 16 Number 9
There are two major themes to this issue that interact at several levels. It is my belief that dealing with these themes is critical to optimum patient care.
The first theme is the importance of cardiovascular health. While most patients think of this in terms of their cholesterol, the real situation is more complex. Metabolic syndrome, which includes insulin resistance, pre-diabetes or diabetes, visceral obesity and hypertension, is a huge issue for men with prostate cancer. This is true before their cancer diagnosis and even more so during treatment.
Cholesterol is part of this picture, but in a very specific manner. With metabolic syndrome, there is commonly an elevation of serum triglycerides and a lowering of the HDL, the “good cholesterol.” While the total LDL cholesterol may be mildly elevated, the magnitude of the elevation often underestimates the true risk of heart attack and stroke. It turns out that LDL cholesterol does not dissolve in blood, but breaks up into lipid particles. The number and size of these particles turn out to be quite important. In fact, over the past several years, there have been eight major consensus conferences on the relative importance of the LDL particle number and size compared with the total LDL. All eight conferences concluded that when the two measures disagree, the particle number was the more accurate indicator of risk. Mayo Clinic Preventative Cardiology has a nice set of YouTube videos on this subject.
The second major theme of this issue is on the range of side effects seen during hormonal therapy. We have just discussed the cardiovascular issues. Dr. Giorgio Gandaglia discusses his work on the kidney damage seen during treatment with LHRH agonists such as Lupron, Eligard, Trelstar, and Zoladex. This problem seems to be specific for this drug family. Surgical castration also lowers testosterone levels, but does not cause kidney damage.
In our February 2015 issue, we featured Dr. E. David Crawford’s views on Firmagon (degarelix). Firmagon reduces testosterone by a different mechanism than the LHRH agonists and does not appear to cause renal damage. I think it is time for us to begin to rethink how we reduce testosterone during hormonal therapy. While Lupron and related drugs are currently the standard, their use may need to be reconsidered.
The final major theme is the PSA doubling time. I should tell you that the papers published by Dr. Stephen Freedland had a major impact on my thinking about prostate cancer. The most common new patients we see are those with a PSA-recurrence after surgery or radiation therapy. With his publications, I had a very accurate tool to judge how threatening a patient’s cancer might be. Frequently, I will find that a patient is at much greater risk for cardiovascular disease than prostate cancer. In fact, hormonal therapy or even radiation therapy can easily be more dangerous than the cancer. In such patients, we will first focus on addressing the issues fueling their cardiovascular risk. We advise patients on diet and exercise.
When these are not sufficient, we are aggressive in the use of drugs. Interestingly, as the cardiovascular risks are reduced, PSA-doubling time often slows.
Dr. Neil Fleshner is doing important work on Metformin. Why did I not make this a fourth theme? I think Metformin relates to each of the other three themes. In randomized trials, metformin is one of the most effective treatments for metabolic syndrome. As you have heard, hormonal therapy exacerbates metabolic syndrome. In a randomized trial, Metformin largely prevented this adverse effect of hormonal therapy. Men actually lose weight when Metformin is added to standard hormonal therapy. So, in our clinic, we find ourselves using Metformin to manage metabolic syndrome. As Dr. Fleshner pointed out, Metformin may actually have anticancer activity. Right now, that is icing on the cake as its wide spread use is clearly warranted as management for metabolic syndrome, particularly when diet and exercise alone are not enough.
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