Neurocognitive effects of androgen deprivation therapy and new hormonal agents in a sample of patients with metastatic prostate cancer

Abstract

Introduction Although the growing treatment landscape for metastatic prostate cancer (mPC) has revealed new opportunities, it has also provided challenges, such as undesirable side effects. The aim of the present study was to provide further data on domain-specific cognitive impairments in mPC patients with androgen deprivation therapy (ADT) and new hormonal agents. Methods Fifty-eight patients (71 ± 8 years) with mPC were investigated using a cross-sectional design. All patients had received some form of ADT (93% had received luteinizing hormone-releasing hormone (LHRH) analogs/antagonists), 66% had received chemotherapy, and 84% had received anti-resorptive therapy. We evaluated learning and memory, processing speed, and executive functions, as recommended by the International Cognition and Cancer Task Force, to determine neurocognitive deficits. Results Patients treated with ADT scored significantly lower on all neurocognitive tests and showed significantly more neurocognitive deficits (38–62%) than age-adjusted reference samples (16%, p < 0.05). Cognitive deficits were mild in most cases and predominantly affected visuomotor processing speed (48%). Moderate and severe deficits were found in 11% and 5% of patients, respectively, with word fluency as the predominant deficit (23%). No associations were found between the type or duration of treatment and the severity of cognitive deficits. Conclusions Treatment of mPC with ADT is correlated with neurocognitive deficits in several cognitive domains. Language skills and processing speed were most frequently impaired. However, a consistent pattern of cognitive impairment was not identified. Neurocognitive deficits should be considered in phase III and IV trials. Trial registration The study was registered in the German Clinical Trials Registry (DRKS00017727).

Treatment-Related Cognitive Impairment in Patients with Prostate Cancer: Patients’ Real-World Insights for Optimizing Outcomes

“…At the time of publication, there is inconsistent data for ADT-induced CI, particularly regarding extent to which ADT can affect cognition in specific cognitive domains [ 16 , 17 , 26 ]. Additionally, potential single-agent therapeutic causes of CI and specific cognitive domains remain unclear [ 17 , 27 ].…”

“…At the time of publication, there is inconsistent data for ADT-induced CI, particularly regarding extent to which ADT can affect cognition in specific cognitive domains [ 16 , 17 , 26 ]. Additionally, potential single-agent therapeutic causes of CI and specific cognitive domains remain unclear [ 17 , 27 ]. While ADT may dominate the PCa treatment landscape, it is important to note that treatment-related CI has been documented in PCa and other cancers with multiple therapies, including chemotherapy, hormonal therapy, AR pathway inhibitors, and statins [ 8 , 13 , 15 , 28 – 31 ].…”

Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood

“…There are conflicting data in the literature about the relationship between ADT and cognitive function decline, but recent evidence supports these changes, particularly in language skills and processing speed [91,92]. A meta-analysis of 12 studies comprising 13,524 participants examined the cognitive effects of second-generation anti-androgen therapy (abiraterone, apalutamide, darolutamide, and enzalutamide) in men treated for prostate cancer and found a statistically significant increase in the risk of cognitive toxic effects such as disturbed attention, memory impairment, cognitive disorder, and amnesia with treatment compared to placebo [93].…”

Cognitive effects of long‐term androgen deprivation therapy in older men with prostate cancer

“…To date, however, studies examining the effects of ADT on cognition have neither exclusively focused on men over 65 years old nor beyond 1 year of ADT. 20,21 This may explain why studies on cognitive difficulties in the PCa population have had mixed results, 6,13,15,16,[21][22][23] with some reporting a significant relationship between ADT and cognitive impairment while others do not. One possible explanation is the broader age range of patients included, from as early as 50 years of age, 14,20,24 which can mask the impact of older age on cognitive performance due to the heterogeneity between younger, middle and older age cohorts.…”