Is ADT Linked to Dementia in Men with Prostate Cancer Receiving Definitive Radiotherapy?

A new study suggests there is no link between the use of androgen deprivation therapy (ADT) and dementia in men with non-metastatic prostate cancer who received definitive radiotherapy. This finding, published in JAMA Oncology, contradicts other studies on the topic.

Previous research has found a strong, statistically significant association between ADT use and both dementia and Alzheimer disease in men with prostate cancer. However, these investigations included men with localized and metastatic disease who received a variety of different treatments.

However, in this new study, Rishi Deka, PhD, of the Department of Radiation Medicine and Applied Sciences, University of California San Diego School of Medicine, La Jolla, California, and colleagues report that there appears to be no statistically significant increase in the risk of any dementia, vascular dementia, or Alzheimer disease in this patient population.  

The researchers conducted an observational cohort study that included men diagnosed with non-metastatic prostate cancer at the US Department of Veterans Affairs. All participants were diagnosed between January 1, 2001, and October 31, 2015, and received definitive radiotherapy with or without ADT. Men with a prior diagnosis of mild cognitive impairment, stroke, or dementia, or a diagnosis of dementia within 1 year of prostate cancer diagnosis, were excluded. Researchers also excluded men who underwent other treatment modalities, including radical prostatectomy; men who did not receive definitive treatment; men who received ADT more than 1 year after their prostate cancer diagnosis; and those who received chemotherapy as a component of their treatment.

The cohort included 45,218 men with a median follow-up of 6.8 years. Only 1,497 patients were diagnosed with any dementia during the study follow-up. There were 335 cases of vascular dementia, 404 cases of Alzheimer disease, and 758 cases listed as other or unclassified dementia.

The authors noted that since the study focused on only radiotherapy-treated patients, the results of this study may not be generalizable to patients with prostate cancer who are treated with other modalities.

Judd W. Moul, MD, a Professor of Surgery and the Director of the Duke Prostate Center at Duke University Medical Center, Durham, North, Carolina, said the findings are not surprising. “This is shorter-term ADT with radiotherapy, so I would not expect less than 3 years of ADT to be associated with dementia,” Moul told Cancer Network. “The more important question is whether long term (> 3 year[s]) of ADT use/continuous long-term use is associated with dementia.”

Moul said that future studies should examine whether ADT combined with long-term novel oral agents, such as abiraterone and enzalutamide, is associated with brain dysfunction in advanced prostate cancer.