Men treated with androgen-deprivation therapy for advanced prostate cancer appear to be at risk for cognitive decline within 6 months of starting therapy, investigators found in a controlled comparison study.

The results, if confirmed, suggest that discussions of the risks and benefits of androgen-deprivation therapy (ADT) should include the possibility of cognitive problems, said Brian D. Gonzalez, Ph.D., and his colleagues from the Moffitt Cancer Center in Tampa.

“Clinicians may also consider inquiring about changes in cognitive functioning that may have occurred after starting ADT and refer patients for assessment and treatment as needed,” they wrote in the Journal of Clinical Oncology.

Because there is, at best, mixed evidence of potential cognitive changes in men undergoing ADT, the investigators conducted cognitive assessments of 58 men within 21 days of starting on ADT and at 6 and 12 months. They compared the results with those of age- and education-matched controls, including 84 with prostate cancer treated with prostatectomy alone and 88 men without prostate cancer.

They used a battery of neuropsychological tests, including validated measures of verbal memory, visual memory, attention, executive function, and cognitive reserve. They compared mean cognitive performance scores using mixed models and cognitive impairment using generalized estimating equations.

They found that there were no differences at any time point in either mean-level cognitive performance nor impaired cognitive performance between the prostatectomy-only controls and the controls without prostate cancer. Therefore, the two groups were combined into a single, larger control cohort.

The men who received ADT were not different from controls at baseline in terms of impaired cognitive performance, but over time they had significantly higher rates of impaired cognitive performance relative to controls (P = .01), and at both the 6-month (P < .05) and 12-month (P < .05) intervals, Dr. Gonzalez and his associates reported (J. Clin. Oncol. 2015 May 11 [doi:10.1200/JCO.2014.60.1963]).

In logistic regression analysis, neither age, baseline cognitive reserve, depression, fatigue, or the presence of hot flashes moderated the effects of ADT on change in impaired cognitive performance.

The authors noted that their findings contradict those of a previous study ( J. Clin. Oncol. 2010;28:5030-37 ), in which investigators found no evidence of higher rates of impaired performance either overall or on specific tests between ADT-treated men and controls over 12 months. They said that the earlier study, however, relied on less stringent criteria of impairment.

“Interestingly, both studies found evidence suggesting that practice effects (ie, improvement over time as function of repeated exposure to same tests) were limited primarily to control groups,” they wrote.

The study was supported by National Cancer Institute grants. Dr. Gonzalez reported having no conflicts of interest to disclose.


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