Androgen Deprivation Therapy for Prostate Cancer and Risk of Dementia

Highlights:

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.
Depending 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 dementia.

Androgen deprivation therapy for prostate cancer may be associated with an increased risk for development of dementia, 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 Study

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 cancer.

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 dementia development.
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.

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‘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.’

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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 dementia.

Other Highlights of the Study

The study has employed an informatics approach with a 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 Alzheimer’s dementia). The study has used new techniques to extract relevant bio-medical data from ordinary patient medical records.

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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.

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Takeaway from the 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.
The 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.
Prostate cancer patients receiving ADT should refrain from making changes to their medications and dosage without first consulting their doctors.

Why the Authors Chose a Retrospective Study Over a Prospective Study

One of the senior authors of the study Dr Shah remarked that their study of analyzing patient records took only about a few weeks.

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"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.

Pitfalls of 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 completely wrong."

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 approach.

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.

Reference

Androgen Deprivation Therapy and Future Alzheimer’s Risk - (http://jco.ascopubs.org/content/34/6/566.abstract?ijkey=c63bb5810173020cbb376f9ee7b36636472ad690&keytype2=tf_ipsecsha)

Source-Medindia

Androgen Deprivation Therapy for Prostate Cancer and Risk of Dementia – A Retrospective Study