Department of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Prostate Cancer Prostatic Dis. 2017 Sep;20(3):259-264. doi: 10.1038/pcan.2017.10. Epub 2017 Mar 28.
Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we synthesize the literature on the association of ADT for the treatment of prostate cancer with dementia risk.
We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (for example, ADT versus no-ADT; continuous versus intermittent ADT) using PubMed (1966-present), Web of Science (1945-present), Embase (1966-present) and PsycINFO (1806-present). The search was undertaken on 4 December 2016 by two authors. We meta-analyzed studies reporting an effect estimate and controlling for confounding. Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity per the I statistic, respectively. Small study effects were evaluated using Egger and Begg's tests.
Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50 541 individuals, showed an increased risk of dementia among ADT users (hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.08-2.00; P=0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05-2.02; P<0.001) and Alzheimer's disease (HR, 1.25; 95% CI, 0.99-1.57; P=0.06). There was no evidence of bias from small study effects (Egger, P=0.19; Begg, P=1.00).
The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased dementia risk. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.
雄激素剥夺疗法（ADT）治疗前列腺癌可能会增加痴呆的风险，但现有研究结果存在矛盾。本研究旨在综合评估 ADT 治疗前列腺癌与痴呆风险之间的相关性。
我们通过计算机检索 PubMed（1966 年至今）、Web of Science（1945 年至今）、Embase（1966 年至今）和 PsycINFO（1806 年至今），纳入 ADT 治疗前列腺癌患者与非 ADT 治疗或低暴露于 ADT 治疗患者（如 ADT 与非 ADT 治疗、连续 ADT 与间断 ADT）比较，发生痴呆的相关研究，检索日期截至 2016 年 12 月 4 日，由两名作者独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用固定或随机效应模型进行荟萃分析。
共纳入 9 项研究，其中 7 项研究报告了痴呆风险的调整后效应估计值。纳入 50541 例患者的痴呆综合结局（包括所有类型痴呆）的随机效应荟萃分析结果显示，ADT 治疗增加痴呆风险（风险比 1.47，95%置信区间 1.082.00，P=0.02）。我们分别对报告全因痴呆（风险比 1.46，95%置信区间 1.052.02，P<0.001）和阿尔茨海默病（风险比 1.25，95%置信区间 0.99~1.57，P=0.06）的研究进行荟萃分析。未见小样本研究偏倚的证据（Egger 检验，P=0.19；Begg 检验，P=1.00）。
目前的综合证据表明，ADT 治疗前列腺癌可能与痴呆风险增加相关。应与患者讨论 ADT 所致潜在神经认知功能缺陷问题，并前瞻性评估。
