以統合分析探討前列腺癌患者使用去勢療法後發生認知功能障礙之風險

研究背景：去勢治療係轉移性前列腺癌或局部晚期侵犯型前列腺癌之主要治療基石，惟去勢治療是否會增加後續罹患認知功能障礙與受影響之認知功能領域則尚未有定論，本研究將藉由統合分析方式，探討前列腺癌患者使用去勢療法後發生認知功能障礙之風險、造成顯著風險增加之重要干擾因子及受影響之認知功能領域。研究方法：本研究利用交集前列腺癌、去勢療法、認知或失智等相關同義字做為主要搜索關鍵字，搜尋包含Pubmed、Embase、Medline、Cochrane Library、華藝線上圖書館等五個資料庫之世代研究，主要結果係各組罹患認知功能障礙之人數比整合結果、校正風險比整合結果、各組於第6個月或第12個月後與基準相比認知測驗下降2個標準差之人數比整合結果、各組於第6個月或第12個月後與基準相比之標準化平均偏差整合結果。為降低收納論文間之異質性，結果皆以隨機模式(random effect)進行整合。本研究另依各文獻控制之干擾因子數目及是否控制年齡、心血管疾病、糖尿病、抽菸、高血壓或使用抗血壓藥、種族、癌症病史、中風、慢性腎臟疾病、高血脂、憂鬱症、抗血小板藥、抗凝血藥、使用statin等共14種干擾因子作為次分析之變項，以找出會顯著影響相關性之干擾因子。研究結果：人數比整合結果(勝算比：1.53；95%信賴區間：1.37-1.69)及校正風險比整合結果(校正風險比：1.15；95%信賴區間：1.08-1.22)皆顯示接受去勢治療者後續罹患認知功能障礙之風險顯著較高。整體認知功能會隨治療時間變長而下降，接受6個月(標準化平均偏差：-0.13；95%信賴區間：-0.23至-0.03；p=0.01)與接受12個月(標準化平均偏差：-0.75；95%信賴區間：-1.14至-0.36；p=0.0002)之去勢治療後，整體認知功能與未接受治療之前列腺癌者差異達顯著，且接受12個月去勢治療後之視覺空間/執行功能(標準化平均偏差：-0.13；95%信賴區間：-0.25至-0.00；p=0.04)、語言(標準化平均偏差：-3.30；95%信賴區間：-6.17至-0.43；p= 0.02)、記憶(標準化平均偏差：-3.22；95%信賴區間：-6.03至-0.41；p=0.02)等認知領域皆會顯著下降。當文獻控制6項以上干擾因子，且控制因子中若包含心血管疾病、糖尿病、抽菸、高血壓或使用抗血壓藥等四種干擾因子時，會顯著增加後續罹患認知功能障礙之風險。結論：依本研究整合結果，倘病人具有心血管疾病、糖尿病、抽菸、高血壓等情況時，接受去勢治療後罹患認知功能障礙之風險會顯著增加，且接受12個月以上之去勢治療者，其執行/視覺空間功能、語言、記憶等認知領域會顯著下降，倘病人屬接受治療後會發生認知功能障礙之高風險族群且當治療療程接受12個月以上者，建議需注意病人之認知功能，尤其是執行/視覺空間功能、語言、記憶等認知領域。

關鍵字

前列腺癌；去勢治療；統合分析；認知功能障礙

並列摘要

Background：Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic or localized advanced prostate cancer. However, whether ADT can increase the subsequent risk of cognitive impairment is still controversial. Therefore, the study used meta-analysis to explore the association between ADT and cognitive impairment, important interfering factors that significant increasing the risk of cognitive impairment, and the most influenced cognitive domain. Methods：The study used prostate cancer, ADT, cognition, dementia and some synonyms as searching keywords to carry out electronic search in Pubmed, Embase, Medline, Cochrane Library and Airiti Library. The primary outcomes included odds ratio, HR, the odds ratio in each group decreasing by 2 standard deviations in the cognitive tests at the 6th and 12th months, and the standard mean difference (SMD) at the 6th and 12th months compared with the baseline of each group. All of the effects were pooled using random effects models to reduce the heterogeneity. Besides, the study stratified by the amount of controlled confounding factors in each study and by whether controlled for age, cardiovascular disease, diabetes, smoking, hypertension or use anti- hypertension drugs, race, history of cancer, stroke, chronic kidney disease, hyperlipidemia, depression, antiplatelet drugs, anticoagulants, and the use of statin in the secondary analysis to find out which one of the confounding factors can significantly affect the correlation. Result：The integrated result of the numbers of the events and total participants (OR=1.53, 95%confidence interval(CI)=1.37-1.69) and HR(HR=1.15, 95%CI=1.08-1.22) indicated those who received ADT is associated with cognitive impairment. The overall cognitive function will decrease as the treatment become longer. For those who received ADT for 6 months (SMD=-0.13, 95%CI=-0.23 to -0.03; p=0.01) or 12 months (SMD= -0.75, 95%CI=-1.14 to -0.36; p=0.0002), the overall cognitive function were significantly worse. For those who received ADT for 12 months, the visuospatial/executive function (SMD=-0.13, 95%CI=-0.25 to -0.00, p=0.04), language (SMD=-3.30, 95%CI=-6.17 to -0.43, p=0.02), memory (SMD=-3.22, 95%CI=-6.03 to -0.41, p=0.02) were significantly worse. When the studies controlled at least 6 confounding factors and specifically when the factors contain cardiovascular diseases, diabetes, smoking, hypertension/anti-hypertesion drugs, the result showed the subsequent risk of cognitive impairment can significantly increase in ADT group compared with the control group. Conclusions：Based on the integrated results of the study, if patients were with cardiovascular diseases, diabetes, smoking, hypertension or use anti- hypertension drugs, the risk of cognitive impairment will significantly increase after receiving ADT. The executive/visuospatial function, language, and memory will be significantly decline after receiving ADT for more than 12 months. If the patient belongs to the high-risk group that will occur cognitive impairment after receiving ADT more than 12 months, it is recommended to pay attention to the patient’s cognitive function especially in the executive/visuospatial function, language and memory.

並列關鍵字

prostate cancer ； ADT ； Meta-Analysis ； cognitive impairment

參考文獻

[1] Stoch SA, Parker RA, Chen L, Bubley G, Ko YJ, Vincelette A, et al. Bone Loss in Men with Prostate Cancer Treated with Gonadotropin-Releasing Hormone Agonists. J. Clin. Endocrinol. Metab. 2001;86(6):2787-2791.

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