Androgen deprivation therapy for prostate cancer ups dementia risk

Adult men with prostate cancer who have increasing exposure to androgen deprivation therapy (ADT) are at greater risk of dementia, according to a US study.

“The potential of a higher risk of dementia in men being treated with ADT should be balanced with a careful and complete discussion of the needs and benefits of ADT in those being considered for such treatment,” the researchers said.

This retrospective analysis was performed on 13,570 men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. Onset of dementia following primary treatment was the primary outcome. ADT exposure was articulated as a time-varying independent variable of total ADT exposure.

The researchers used a propensity score to estimate the probability of receiving ADT. They also performed Cox proportional hazards regression to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments.

Of the men, 317 (2.3 percent) were diagnosed with dementia after a median of 7.0 years of follow-up. After adjustment, cumulative ADT significantly correlated with dementia (hazard ratio [HR], 2.02, 95 percent confidence interval [CI], 1.40‒2.91; p<0.01). [J Urol 2022;207:832-840]

An association was also observed between ADT use and dementia (HR, 1.59, 95 percent CI, 1.03‒2.44; p=0.04) in a subset of 8,506 men, where propensity score was matched by whether or not they received ADT. On the other hand, no association was seen between primary treatment type and dementia onset in the 8,489 men in the cohort who did not receive ADT.

Several observational studies had reported conflicting results on the incidence of dementia in men who had received ADT for prostate cancer. [JAMA Netw Open 2019;2:e196562; Eur Urol Oncol 2021;4:66-72; JAMA Oncol 2018;doi:10.1001/jamaoncol.2018.4423; J Clin Oncol 2017;doi: 10.1200/JCO.2016.69.6203]

The first study to find a link between ADT and an increased risk of Alzheimer’s disease used a novel text-processing platform to analyse the electronic medical record data in a retrospective cohort of patients in two large medical centres. [J Clin Oncol 2016;34:566-571]

“Existing studies that have assessed the association between Alzheimer's and ADT included patients with localized and metastatic disease, treatments with curative and palliative intent, and ADT use in the up-front or recurrent setting,” the researchers said.

“The heterogeneity inherent to the different treatment modalities and disease stages may contribute to substantial selection bias, and unmeasured factors may confound the relationship between ADT use and dementia,” they added.

The results of the current study provided additional evidence that ADT exposure could lead to dementia onset and stressed the importance of cognitive assessment in patients undergoing ADT.

“Awareness of potential sources of cognitive dysfunction such as ADT and other androgen-targeted therapies and the prompt identification of early, treatment-related symptoms are important to ensure that any effect on functional capacity and quality of life is minimized,” the researchers said.