Cardiovascular Deaths Not Linked with ADT for Prostate Cancer but Lower All- Death Risk May Be
Study should be 'generally reassuring' to most men with unfavorable-risk prostate cancer considering ADT, because it was
associated with improved survival
Dec. 7, 2011 -
Although previous research has indicated that the use of androgen deprivation therapy (ADT) to treat men with unfavorable-risk, nonmetastatic
prostate cancer may increase the risk of dying from cardiovascular causes, a new study failed to find the link. It did find, however, lower risk of prostate cancer-specific death and all-cause death with ADT.
The report on the meta-analysis of previous randomized trials using ADT to suppress the
production of male sex hormones will be published in the December 7 issue of the Journal of the American Medical Association (JAMA).
ADT in the form of a gonadotropin-releasing hormone (GnRH) agonist is a mainstay of prostate cancer treatment. The
finding in several studies that this therapy may increase the risk of cardiovascular death prompted a U.S. Food and Drug Administration safety
warning and a joint statement by multiple medical societies to raise awareness of a potential linkage between ADT and cardiovascular events,
according to background information in the article.
However, other studies have not confirmed these findings.
Paul L. Nguyen, M.D., of the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School,
Boston, and colleagues performed a meta-analysis of randomized controlled trials to determine whether ADT is associated with cardiovascular
mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer.
ADT therapy works well with intermediate grade cancer, not so well with low grade; only two grades tested in this trial
graphs of prostate cancer cases and deaths 1987-2007 below story
July 15, 2011 Adding short-term androgen deprivation therapy (ADT) to radiation therapy for men with early-stage,
intermediate risk prostate cancer made a significant improvement in their overall survival after 10 years, according to a clinical trial
supported by the National Cancer Institute (NCI), part of the National Institutes of Health. Benefits of the combined treatment were not seen
for men with low-risk prostate cancer. Read more, info on prostate cancer...
A review of the medical literature identified eight randomized trials (4,141 patients) that met inclusion criteria for
the cardiovascular death meta-analysis. Median (midpoint) follow-up in these trials ranged between 7.6 and 13.2 years.
Among the 2,200 patients who were treated with ADT, there were 255 cardiovascular deaths, corresponding to an overall
incidence of cardiovascular death of 11.0 percent.
For the control group, there were 1,941 patients and 252 cardiovascular deaths, for an overall incidence of 11.2 percent.
Among patients in short-course ADT trials (6 months or less), the incidence of fatal cardiovascular events for ADT vs.
control was 10.5 percent vs. 10.3 percent, respectively.
Among patients in long-course ADT trials (3 years or longer), the incidence of fatal cardiovascular events for ADT was
11.5 percent, vs. 11.5 percent for the control group.
The researchers also found that the age of the patients did not influence the findings, as there was no association
between ADT and cardiovascular death whether the median age was older or younger than 70 years.
There were 443 PCSM deaths among 2,527 patients in the ADT group and 552 PCSM deaths among 2,278 patients in the control
Men receiving ADT had a 31 percent lower relative risk of PCSM, with an incidence of 13.5 percent vs. 22.1 percent for
There were 1,140 total deaths among patients in the ADT group and 1,213 total deaths among patients in the control group,
with analysis indicating that men receiving ADT had a 14 percent lower relative risk of all-cause mortality compared to the control group
(incidence, 37.7 percent vs. 44.4 percent, respectively).
"Overall, the results of our study should be generally reassuring to most men with unfavorable-risk prostate cancer
considering ADT, because it was associated with improved survival without a measurable excess in cardiovascular mortality. But, a few
important points need to be raised.
First, none of the trials were stratified by preexisting cardiovascular comorbidity; therefore, our study cannot exclude
the possibility that a small subgroup of men with underlying cardiac disease (even if controlled) could experience excess cardiovascular
mortality due to ADT. ... A second issue is that although our study assessed total cardiovascular deaths, it could not exclude the possibility
that cardiovascular deaths happen earlier in men receiving ADT," the authors write.
"In conclusion, our meta-analysis of more than 4,000 patients could not find any evidence that ADT increases the risk of
cardiovascular death among men with unfavorable-risk, nonmetastatic prostate cancer, but did find a significant association between ADT and
improved prostate cancer-specific survival and overall survival."
Editorial: Androgen Deprivation Therapy and Competing Risks
An editorial in the same issue points out that "with more than 600,000 patients in the United States with prostate cancer
being treated with ADT", the benefits and short-term and long-term risks of ADT need to be clearly outlined.
William K. Kelly, D.O., and Leonard G. Gomella, M.D., of Thomas Jefferson University, Kimmel Cancer Center, Philadelphia,
write, "... men with cardiac disease who have the highest risks from complications from ADT should follow the appropriate secondary preventive
measures from the American Heart Association (lipid-lowering therapy, antihypertensive therapy, glucose-lowering therapy, and antiplatelet
Although ADT has been part of the treatment regimen for several decades, clinicians treating patients with prostate
cancer are still understanding the short-term and long-term biological effects of biochemical castration but now have better appreciation of
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