Gonzalez Brian D, Jim Heather S L, Booth-Jones Margaret, Small Brent J, Sutton Steven K, Lin Hui-Yi, Park Jong Y, Spiess Philippe E, Fishman Mayer N, Jacobsen Paul B
Brian D. Gonzalez, Heather S.L. Jim, Margaret Booth-Jones, Steven K. Sutton, Hui-Yi Lin, Jong Y. Park, Philippe E. Spiess, Mayer N. Fishman, and Paul B. Jacobsen, Moffitt Cancer Center; and Brent J. Small, University of South Florida, Tampa, FL.
J Clin Oncol. 2015 Jun 20;33(18):2021-7. doi: 10.1200/JCO.2014.60.1963. Epub 2015 May 11.
Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance.
Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations.
ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001).
Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.
接受雄激素剥夺疗法(ADT)治疗前列腺癌的男性可能有认知障碍风险;然而,现有文献中的证据并不一致。我们的研究考察了ADT对认知功能受损的影响,并探索了认知功能受损的潜在人口统计学和基因预测因素。
前列腺癌患者在开始ADT前或开始ADT的21天内(n = 58)以及6个月和12个月后接受评估。年龄和教育程度匹配的仅接受前列腺切除术治疗的前列腺癌患者(n = 84)和无前列腺癌的男性(n = 88)在相似的时间间隔接受评估。参与者提供基线血样用于基因分型。使用混合模型比较平均水平的认知功能;使用广义估计方程比较认知障碍。
与所有对照组相比,随着时间推移,接受ADT者认知功能受损的发生率更高(P = .01)。各组在基线时无差异(P > .05);然而,接受ADT者在6个月和12个月内更有可能出现认知功能受损(两项比较的P均< .05)。基线年龄、认知储备、抑郁症状、疲劳和潮热干扰并未缓和ADT对认知功能受损的影响(所有比较的P≥ .09)。在探索性基因分析中,GNB3单核苷酸多态性rs1047776与ADT组中随着时间推移认知功能受损发生率增加相关(P < .001)。
与匹配的对照组相比,接受ADT治疗的男性在开始ADT后6个月内更有可能出现认知功能受损,并在开始ADT后12个月内持续如此。如果得到证实,这些发现可能对患者关于ADT风险和益处的教育有影响。