Penn study links prostate cancer treatment to dementia

Here's yet another thing for men with prostate cancer to worry about.  A second study has found a connection between treatments that target male hormones and dementia.

Earlier research by a team from the University of Pennsylvania and Stanford University found increased risk for Alzheimer's disease. The new study, from the same institutions, published Thursday in JAMA Oncology,  found that patients who had taken androgen deprivation therapy (ADT) had double the risk for a broader range of dementia diagnoses, including Alzheimer's, senile dementia, vascular dementia, and frontotemporal dementia, compared with similar men with prostate cancer who did not have the treatment.  The study was based on an analysis of the medical records of more than 9,000 men with prostate cancer from the Stanford University health system from 1994 to 2013. Of those patients, 1,826 had received ADT.

The risk of being diagnosed with dementia in five years was 13.7 percent for men over 70 who had ADT, compared with 6.6 percent in men over 70 who did not.  Predictably, the risk was lower in younger men, but the relationship was still the same.  In men under 70, 2.3 percent of those who had ADT got a dementia diagnosis, compared with 1 percent of those who had not had the treatment.

About 500,000 men in the United States are getting ADT,  which suppresses testosterone, the study said. It is considered a first-line treatment in appropriate men, said Alexander Kutikov, a urological surgeon at Fox Chase Cancer Center.  There are no equivalent alternatives.

The hormones are given to men whose cancer has spread or to those with localized disease who received radiation treatment and are considered at mid to high risk for aggressive disease.  In metastatic disease, getting ADT can make the difference between living an average of five years compared with about three with no treatment, said Matthew Zibelman, a medical oncologist at Fox Chase.  Men with slow-growing, metastatic cancer can live for 10 years or more with treatment.

Figuring out the impact of ADT for men with localized cancer is more complex. "I think that's the most complicated prostate cancer discussion I have," Zibelman said. One study found that in men at high and very high risk of recurrent disease, 45 percent who had taken ADT were alive at 10 years, compared with  32 percent who had not.  Studies were mixed on the benefits for men at intermediate risk, he said.   Kutikov said a recent study of patients without metastatic disease found a benefit in those without other health problems but not in those who already were in poor health.

ADT is known to cause unpleasant side effects, such as hot flashes, sexual problems, breast enlargement and tenderness, weight gain, high blood pressure, and fatigue.

The new study shows only an association between the treatment and dementia, not proof that the treatment causes dementia.  However, Kevin Nead, a third-year resident in radiation oncology at Penn's Perelman School of Medicine who was involved in both studies, said the analysis is a strong argument for  doing more research that follows patients throughout their treatment.  "This is an important question that we do need to answer," he said.

He added that he knows some patients will be concerned by his results, but he wouldn't recommend changes in clinical care.  He said doctors find it hardest to decide whether to recommend ADT for patients at intermediate risk.  Further research would be most useful for that group.

"ADT is a hugely beneficial drug," he said. "We don't think this should change clinical practice."

As for why ADT might affect brain function, Nead said there is evidence that low testosterone is associated with greater accumulation of amyloid, one of the key proteins that builds up in the brains of people with Alzheimer's disease.  Testosterone  is also important for protection, growth, and regeneration of neurons.  And ADT has cardiovascular side effects, which are also risk factors for dementia.

In the study, men who got ADT were different from the men who did not.  They were older, less likely to be white, and more likely to smoke.  They were also more likely to have a history of heart disease, diabetes, and other cancers. For the comparison, the researchers attempted to account for the differences by matching them with non-ADT users who were more medically and demographically similar.

Kutikov, who was not involved with the study, praised its sophisticated use of data but said this kind of work has limited value. "This is a really new way of analyzing medical data and the fidelity of that data is unclear," he said.

Kutikov said that the healthiest patients often get surgery and usually do not get ADT.  This kind of matching can go awry when two groups start out so dissimilar, he said. It could be that something about the ADT users' long-term underlying health raised their risk for dementia.  He also pointed out that researchers did not have data on how well the patients' brains were working before they started treatment.