Androgen Prostate Cancer Therapy Linked to Dementia, Prostate Treatments Questioned
Men diagnosed with prostate cancer now need to know two things about prostate cancer treatment. The first is that prostate cancer treatment doesn’t significantly reduce the risk of dying from the disease. At least within the next 10 years.
The second is about one of the primary prostate cancer treatments, called androgen deprivation therapy. This prostate cancer therapy has been shown to double the risk of dementia. This is in addition to other adverse side effects of ADT drugs.
What is androgen deprivation therapy?
As mentioned, androgen deprivation therapy (ADT) is one of the primary treatments for prostate cancer.
There are three methods of androgen deprivation therapy. These include what is basically drug castration. This means blocking the production of testosterone. Drug castration is achieved with either LHRH agonist or a LHRH antagonist drugs.
The LHRH hormone activates luteinizing hormone. LHRH stimulates the release of luteinizing hormone by the pituitary gland. Luteinizing hormone in turn stimulates the production of testosterone in the testes.
Both the LHRH agonists and the LHRH antagonists prevent the pituitary gland from releasing luteinizing hormone. This effectively blocks the production of testosterone.
The drugs given to stop the LHRH hormones include leuprolide, goserelin and triptorelin. These are typically injected.
Another drug therapy is called antiandrogen therapy. This means blocking the prostate cells’ ability to bind and use testosterone. Drugs like flutamide, nilutamide and enzalutamide are given in pill form.
Rarely but sometimes, doctors will perform surgical castration. This means removing the testes. Because this is permanent, ADT drug strategies are typically utilized.
Regardless of which method is used, there are many indications that ADT therapy is only a temporary deterrent for cancer. That’s because after the initial cancer growth is slowed, prostate cancer cells tend to adapt to the lack of testosterone. They often continue to grow anyway.
Plus, there are numerous side effects of any of these ADT therapies. Potential side effects include low energy levels, low libido, hot flashes, higher risk of bone fractures and osteoporosis, anemia, increased risk of metabolic syndrome and cardiovascular disease, depression and cognitive effects.
Androgen deprivation therapy boosts Alzheimer’s risk
Researchers from Stanford University and the Mount Sinai School of Medicine followed 16,888 men who were diagnosed with prostate cancer at the Stanford and Mount Sinai medical centers.
Of these, 2,497 men received androgen deprivation therapy. They were followed up for an average of 2.7 years. The researchers found those given the ADT therapy were 88 percent more likely to be diagnosed with Alzheimer’s disease. This is compared to those not given the ADT therapy.
“Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer’s disease in a general population cohort.”
Dementia risk even higher after ADT therapy
The same researchers conducted another study published in October of 2016. This time, they followed 9,272 men with prostate cancer. This included 1,826 men treated with ADT.
The researchers found an even higher increased risk of dementia for those given ADT. The average increased risk of dementia was more than double for those given ADT. Dementia risk increased by 217 percent when Alzheimer’s disease was included. When Alzheimer’s disease was excluded, the increased risk of dementia was 232 percent.
One of the researchers, Dr. Nigam Shah, underscored this risk of ADT therapy:
“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.”
What about radiation and surgery for prostate cancer?
The comment from Dr. Shah above relates to an October, 2016 study from the University of Oxford and the University of Cambridge. The researchers followed 82,429 men between 50 and 69 years old. Of those, 2,664 received a prostate cancer diagnosis. Of these, 1,643 were monitored for ten years.
Of the 1,664 men, 545 received radiation treatment to kill the cancer cells. Another 553 men received surgery to remove the cancer cells. And 545 men were not treated. They were given active monitoring – meaning they were simply watched.
After ten years, the survival rates for all the groups were close. There wasn’t much difference between the radiation group, the surgery group and the no-treatment group.
Only eight men died of cancer in the ten years of no treatment. This compares to five men in the surgery group and four in the radiation group.
In terms of deaths for other causes, there was also little difference between the treatment and the non-treatment groups.
Yes, there were three more deaths in the no-treatment group. But statistically, this is nearly a dead heat. This makes the 10-year survival rate of no treatment 98.8 percent. This compares to 99 percent in the surgery group and 99.6 in the radiation group. Typically, a difference of at least 10 percent is needed to become a significant research result. Because the difference was under 1 percent, the difference is called non-significant.
The researchers concluded:
“The results show that death from prostate cancer in such men remained low at a median of 10 years of follow-up, at approximately 1%, irrespective of the treatment assigned, a rate that is considerably lower than was anticipated when the trial commenced.”
That is, no significant difference between those who were treated and those who were not treated. Because “active monitoring” was considered a “treatment,” the researchers referred to it as such.
It is notable that the result was lower than anticipated by the researchers. The research was conducted by dozens of doctors who specialize in prostate cancer treatment. They assumed that their treatments were radically saving lives.
Their assumptions were wrong.
This is not to say that radiation and surgery treatments don’t sometimes help. The research did find some of those who received radiation or surgery had less clinical progression of their cancers compared to non-treatment. The non-treatment group had 112 men whose cancers progressed. This compared to 46 men in the surgery group and 46 men in the radiation group.
This doesn’t necessarily mean those whose cancer progressed in non-treatment group will die earlier of the cancer. Ten year survival rates are often used as the gold standard of cancer survivability. That’s because cancer can develop considerably in ten years.
Interestingly, the number of patients who received the surgery or radiation whose cancer progressed was also considerable. Assuming these treatments are supposed to halt the growth of the cancer, there were still 8 to 9 percent of those treated with radiation or surgery whose cancers remained and progressed over the 10 years.
New decisions to make
This new information presents a man diagnosed with prostate cancer with a new paradigm. The question likely comes down to age at the time of diagnosis, and the relative progression of the disease.
These are not easy questions to answer for everyone. They are best discussed with one’s doctor, and perhaps with a second opinion from a specialist.
We can contribute by providing additional research relating to natural prostate strategies:
Nead KT, Gaskin G, Chester C, Swisher-McClure S, Dudley JT, Leeper NJ, Shah NH. Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk. J Clin Oncol. 2016 Feb 20;34(6):566-71. doi: 10.1200/JCO.2015.63.6266.
Stanford Medicine. Common prostate cancer treatment linked to later dementia, researcher says. Oct 16, 2016
Petros Sountoulides and Thomas Rountos, Adverse Effects of Androgen Deprivation therapy for Prostate Cancer: Prevention and Management. ISRN Urology, vol. 2013, Article ID 240108, 8 pages, 2013. doi:10.1155/2013/240108
Nead KT, Gaskin G, Chester C, Swisher-McClure S, Leeper NJ, Shah NH. Association Between Androgen Deprivation Therapy and Risk of Dementia. JAMA Oncol. 2016 Oct 13. doi: 10.1001/jamaoncol.2016.3662.
Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group.. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424.