Cognitive Dysfunction with Androgen-Deprivation Therapy

Summary and Comment |
May 15, 2015

Cognitive Dysfunction with Androgen-Deprivation Therapy

  1. Robert Dreicer, MD, MS, FACP, FASCO

Prostate cancer patients who received ADT had higher rates of impaired cognitive performance at 6 and 12 months than those who did not receive ADT.

  1. Robert Dreicer, MD, MS, FACP, FASCO

Clinicians who treat prostate cancer patients with androgen-deprivation therapy (ADT) are skilled at recognizing and managing adverse effects, such as hot flashes, metabolic syndrome/weight gain, muscle mass loss, and osteoporosis. More difficult to assess and manage is the potential impact of ADT on cognitive function. Compelling data on this topic have been in short supply, but in a high-volume prostate cancer practice a substantial minority of patients report changes in cognitive function, often described as a loss of “sharpness” following ADT.

To assess the effect of ADT on cognitive performance, investigators prospectively studied three groups of individuals: 58 prostate cancer patients receiving ADT, 84 prostate cancer patients not receiving ADT (prostate cancer controls), and 88 men without prostate cancer (healthy controls). Prostate cancer patients receiving ADT had either nonmetastatic or asymptomatic metastatic prostate cancer. Prostate cancer patients not receiving ADT had undergone prostatectomy and had no evidence of disease. Both control groups were matched by age and educational level; prostate cancer controls were further matched by time from prostate cancer diagnosis. The researchers used validated neuropsychological testing and self-reported depression and symptoms assessment to evaluate verbal/visual memory, attention, executive function, and cognitive reserve. Exploratory analyses of single-nucleotide polymorphisms also were prospectively assessed.

Because no differences in cognitive function were observed between the control groups, data from them were combined for analysis. Rates of impaired cognitive function were similar between the ADT group and the control groups at baseline. However, ADT patients demonstrated greater dysfunction over time, including a 70% increase in impaired performance at 6 months and a >50% increase at 12 months (P<0.05 for both).

Comment

In addition to the clinical data noted above, the investigators found that a single-nucleotide polymorphism, rs1047776 in GNB3, was associated with increased rates of impaired cognitive performance over time, which will likely lead to additional investigation into the underlying molecular genetics of ADT toxicity. These data may inform risk/benefit discussions in clinical settings in which ADT use is not well defined.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP, FASCO at time of publication Consultant / Advisory board Medivation; Genetech/Roche; Bind Pharmaceuticals; Astellas Editorial boards Urology; Clinical Genitourinary Cancer; Current Urology Reports Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee); American Board of Internal Medicine (member, Medical Oncology Test Writing Committee); Bladder Cancer Advocacy Network (member, scientific advisory board)

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