A new retrospective study of patient medical records suggests that men with prostate cancer who are treated with testosterone-lowering drugs are twice as likely to develop dementia within five years as prostate cancer patients whose testosterone levels are not tampered with.
The study, by researchers at the Stanford University School of Medicine and the University of Pennsylvania Perelman School of Medicine, also demonstrates emerging techniques for extracting biomedical data from ordinary patient medical records.
The paper describing the research will be published online Oct. 13 in JAMA Oncology. Kevin Nead, MD, DPhil, a resident at the University of Pennsylvania who got his medical degree at Stanford, is the lead author. Nigam Shah, MBBS, PhD, associate professor of biomedical informatics research at Stanford, is the senior author.
Testosterone can promote the growth of prostate tumors, and so clinicians have used androgen deprivation therapy to lower testosterone and other androgens in prostate cancer patients since the 1940s. In the United States, about a half-million men currently receive ADT as a treatment for prostate cancer.
'The risk is real'
A 2015 study by the same authors found an association between ADT and Alzheimer's disease. In the new paper, the team expanded their 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 power.
The team looked at deidentified records from Stanford Medicine's clinical-research data warehouse for nearly 10,000 patients with prostate cancer. Of the 1,829 who received androgen deprivation therapy, 7.9 percent developed dementia within five years, compared with 3.5 percent of those not treated with ADT.
"The risk is real and, depending on the prior dementia history of the patient, we may want to consider alternative treatment, particularly in light of a recent prospective study from the U.K.," said Shah. That study, published in September in The New England Journal of Medicine, revealed that prostate cancer patients randomized to either active monitoring, surgery or radiation therapy all had the same risk of death from the cancer after 10 years. Ninety-nine percent of men in the study survived regardless of initial treatment. These startling results suggest that active monitoring of prostate cancer patients may be as good as early radical treatment and may cause fewer side effects.
And because the actual number of patients possibly at risk for dementia from androgen deprivation therapy is small, it makes sense when weighing the value of prescribing ADT to try to identify which prostate cancer patients might be vulnerable to dementia, said Shah.
The new study adds to a growing body of evidence supporting Stanford Medicine's precision health approach, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
Nead and Shah cautioned that prostate cancer patients who are receiving ADT shouldn't make changes to their medications without talking to their physicians.
"I was surprised at how ubiquitous the effects on all types of dementia were, but I would definitely not alter clinical care based on our results," Nead said. He added that he would like to see a prospective, randomized clinical trial to establish whether ADT can be more firmly linked to an increased risk of dementia and to help identify what kinds of patients might be vulnerable to that increased risk, he said. He anticipates that checking for dementia risk in people treated with ADT will be part of future randomized, clinical trials that have a larger focus.