Alzheimer’s and ADT…some perspectives

To read this blog on my blog site and see previous and future blogs, please click here.

Several of you asked for my perspective on the article that appeared last week in JCO and was widely picked up by the media. The NYT covered it with this headline: “Prostate Cancer Treatment Tied to Alzheimer’s Risk.”  NBC News said, “Common Prostate Cancer Treatment May Double Risk for Alzheimer’s”, then did a reasonable job of placing some perspective on the article in spite of the scary headline.

First, I would point out that this article is representative of the way medical investigators will be able to use BIG DATA in intriguing and effective ways. This team started off with a total of 5.5 million electronic medical records at Stanford and Mt. Sinai and used sophisticated computer algorithms to find 16,888 patients with prostate cancer and then looked further to find new onset Alzheimer’s disease among the 2,397 who received ADT therapy. They were able to control for known Alzheimer’s risk factors such as age and cardiovascular disease in doing their analyses. The statistical methods and mathematics for the study are certainly beyond anything I could understand or effectively comment on, but my congratulations to the investigators on their study!

To compare the risks of developing Alzheimer’s disease from ADT, one needs to know the benefit (if any) from taking ADT. There should be little doubt that a man who presents with painful boney metastases benefits far beyond any risk. Such an individual might expect to live 44 months with ADT alone (and might improve his prognosis to a median survival of 58 months by taking 6 cycles of docetaxel at the onset of ADT (CHAARTED trial). To give a graphical comparison of the Alzheimer’s risk compared to this man’s life expectancy from prostate cancer, I superimposed the Alzheimer’s risk onto the CHAARTED trial survival graph:

What about someone with local disease but high risk based on PSA >20? In one of the larger trials comparing the addition of ADT to radiation vs. radiation alone in such patients, even as short as 4 months ADT resulted in cutting the disease specific mortality at 10 years from 8% to 4% (and improving overall survival from 57% to 62%) Again, this seems like a favorable equation in favor of using ADT, considering the risk of Alzheimer’s disease at 10 years in the new article is 5% with ADT and 4% without ADT. Moreover, the Alzheimer study found that shorter duration of ADT didn’t represent as much risk (< 12 months treatment resulted in an insignificant increase in risk when all the known other risks for Alzheimer’s disease were accounted for).

Thus in the larger context, I think for the majority of men who must consider ADT therapy, the risk of Alzheimer’s disease is small and for most would not be much of a factor to consider. The 5 leading causes of death for men in the United States are heart disease, cancer, unintentional injuries, respiratory disease and stroke (in that order). Alzheimer’s disease comes in at 9th place, representing just 2% of deaths, less than suicide which places 7th at 2.5%. I am currently reading one of the O’Reilly books, “Killing Patton,” which is full of quotes from the famous general. Death, he said, “in time comes to all men.” As a professional soldier, he wanted to die from “the last bullet of the last battle of the last war.” Most of us don’t imagine such glorious endings and would settle for a peaceful death in our sleep after a fine meal with our family, or perhaps, as one of my patients managed, walking back from a river with his fly rod in hand and his hip waders still on. Prostate cancer is terrible, and Alzheimer’s even worse, but most of us are destined to die of something else, and the real message is to live each day honorably and hopefully in the service of a greater cause.