deprivation therapy for prostate cancer
- Androgen deprivation therapy (ADT) forms one of
the mainstays of prostate cancer treatment.
- Men treated
with androgen deprivation therapy are twice as likely to develop dementia
within five years, finds a retrospective study.
on the risk of dementia, alternative forms of treatment may be considered.
- However, prospective, randomized trials may be necessary
to firmly establish a causal relationship between ADT and
be associated with an increased risk for development of
, indicates a recent retrospective study undertaken by Kevin
T. Nead, M.D., M.Phil., formerly of the Stanford University School of Medicine,
California, and now the University of Pennsylvania Perelman School of Medicine,
Philadelphia, and his team of co-authors.
Findings of the
The research team analyzed de-identified
records of nearly 10,000 patients from Stanford Medicine's clinical-research
data warehouse, who had been diagnosed with prostate
- Of the 1,829 (nearly 20%) who received androgen deprivation
therapy (ADT), 7.9 percent developed dementia within five years, compared with
3.5 percent of those not treated with ADT.
- The authors
state that 314 new cases of dementia emerged during a median follow-up of 3.4
years with a median time to dementia of four years.
- The absolute increased risk for development
of dementia among men who received ADT was 4.4 percent at five years, according
to the results.
- Further analysis of data indicates that
men who received ADT for at least 12 months had the highest absolute risk for
- Men, who were 70 years or older and received
ADT were most likely to develop dementia.
The study suggests several possible reasons
for an association between ADT and development of dementia, including
observations that androgens play a role in neuronal growth and health.
‘The likely benefits of androgen deprivation therapy should be weighed in prostate cancer patients to identify those who may be vulnerable to the development of dementia.’
Possible limitations of the study include
using clinical text documentation and billing codes to settle on a diagnosis of
dementia. Being a retrospective study, it also cannot determine a causal
association between the employment of ADT and the risk for development of
Other Highlights of
The study has employed an informatics approach
text-processing method to assess electronic medical records data to study the
use of ADT and the subsequent development of dementia (senile dementia, vascular dementia
, frontotemporal dementia and
). The study has used new techniques to extract relevant bio-medical
data from ordinary patient medical records
An earlier study in 2015 by the same authors
determined a link between ADT and Alzheimer's disease. In the latest study, the
team enlarged upon their earlier work to
include several other forms of dementia
"When we published our last paper, a
letter to the editor pointed out that Alzheimer's is often confused with
vascular dementia," said Shah. "So instead of looking for Alzheimer's
and dementia separately, we decided to aggregate them into a higher-level
category -- all dementias and cognitive decline." Such aggregation could
minimize the question of misdiagnosis, Shah said, and increase the sample size
to provide more statistical weightage to the study.
Takeaway from the
Why the Authors
Chose a Retrospective Study Over a Prospective Study
- The risk between ADT and development of dementia is real, so much
so that alternative forms of therapy may
have to be considered in vulnerable patients.
findings of this study become more relevant in the light of a recent
prospective study in the UK that revealed prostate cancer patients randomly
chosen to receive either active monitoring, surgery or radiation therapy, all
had the same risk of mortality from cancer after 10 years. Ninety-nine percent
of men in the study survived regardless of initial treatment. These shocking results suggest that active
monitoring of prostate cancer patients may be as good as early radical
treatment while causing fewer side effects.
cancer patients receiving ADT should
refrain from making changes to their medications and dosage without first
consulting their doctors.
One of the senior authors of the study Dr
Shah remarked that their study of analyzing patient records took only about a
"We were down to weeks in this one, and
our current efforts, which are funded by the Dean's Office, have gotten us
close to two to three days."
In stark contrast, a prospective, randomized clinical trial to answer the same question
would probably need thousands of patients, would have taken years to complete
and cost many millions of dollars
, said Kenneth Mahaffey, MD, a Stanford
professor of medicine who was not involved in the study.
Additionally, health record analysis offers
powerful tools to determine hypotheses about efficacy and safety that might be
worth further testing in future clinical trials.
Retrospective Health Record Studies
The lack of randomization in health record
studies carries a risk that the results could be misleading, cautioned
Mahaffey. "This work is important," he said, "but there are a
number of examples of such retrospective studies where the results have been
However Dr Shah, claims that the study has been
so designed that the chances of going wrong seem minimal.
For instance, the researchers matched
patients who received ADT and those who did not based on how sick they were.
They have also explicitly as well as empirically estimated the chances of being
wrong by testing associations they knew were not correct, and fine tuning their
He however admits that health records
analysis cannot replace randomized prospective trials. "If we had infinite
funding, we'd do a trial for everything. But we don't have that," he said.
"These cheap, few-week studies can guide us where to point our clinical
trial dollars." Such retrospective studies complement prospective trials.
The authors of the study hope that estimating
dementia risk in people treated with ADT will form part of future randomized
clinical trials having a bigger focus.
- Androgen Deprivation Therapy and Future Alzheimer's
Risk - (http://jco.ascopubs.org/content/34/6/566.abstract?ijkey=c63bb5810173020cbb376f9ee7b36636472ad690&keytype2=tf_ipsecsha)