篩檢方法
撰寫人員:張迺鴻 | 審稿人員:吳慧敏博士 | 審查醫師: 黃柏堅醫師 2014/09/24

攝護腺癌篩檢方法

目前最常見的攝護腺癌防治方法是透過篩檢,也就是針對沒有症狀的男性,利用特定檢查來及早診斷出攝護腺癌,以提高攝護腺癌的存活率,降低其死亡率。

目前常見的攝護腺癌篩檢方式主要包括血清中的攝護腺特異抗原(prostate-specific antigen, PSA)及肛門指診(digital rectalexamination, DRE)二種。

攝護腺特異抗原(prostate-specific antigen, PSA)

檢測血液中的攝護腺特異抗原(以下稱PSA)濃度是否過高被認為是目前較佳的攝護腺癌篩檢工具(Catalona WJ等人, 1994)。PSA為攝護腺所產生的一種穩定性很高的蛋白質,功能在於使精子呈液體狀不致凝結,一般存在於精液中,但在正常情況下血液中亦會有少量PSA 存在。當攝護腺出現癌細胞,易使血液中的PSA濃度升高,因此血中PSA濃度被應用作為檢測是否有攝護腺癌的主要篩檢工具。由於它穩定性高,敏感度及特異 性亦高,因此廣泛被應用在臨床診斷及治療上,是目前最有價值的腫瘤標記之一。目前最被廣泛接受的PSA切點值為4 ng/ml,敏感度可達73%-87%(Gann PH et.al.,1995; Auvinen A 等人, 2005),特異度約為91-93%( Gann PH et.al.,1995; Määttänen L等人, 2007)。

在攝護腺癌篩檢效益的研究,目前僅有PSA經過大型隨機試驗的證明,藉由PSA來進行大規模的族群篩檢可有效降低攝護腺癌的死亡率。根據歐洲針對55歲至69歲民眾的大型隨機試 驗(ERSPC)(Schröder等人, 2009)證實PSA篩檢經九年追蹤後發現可有效的降低20%(95% 信賴區間為2%-35%)的攝護腺癌死亡率,其研究結果顯示,欲避免一個攝護腺癌死亡,需篩檢1410位男性,而經更長期11年的追蹤發現,欲避免一個攝護腺癌死亡,僅需篩檢1055位男性,篩檢效益更為顯著(Schröder等人, 2012)。值得關心的是較早開始的加拿大試驗(Quebec) (Labrie等人, 1999)或與歐洲試驗同時期的美國試驗(PLCO)(Andriole等人, 2009)中則發現受邀參加篩檢及未受邀參加篩檢二組民眾在攝護腺癌的死亡率上並無差異,也就是未發現PSA篩檢有效益,但因加拿大篩檢組中僅有23%實 際接受PSA篩檢,絕大多數的參與者皆拒絕接受研究者的建議,而在美國的研究則是在另一組未受邀請參加PSA篩檢的民眾中,卻又有高達40%-52%的民 眾因自身健康意識或其他原因而自發性的參加PSA篩檢,且PSA篩檢結果為陽性者進一步接受切片檢查的比例相當低,使得這二個隨機試驗在研究品質上較有問 題,其研究結果所提供的參考度也就大打折扣了。

值得注意的是攝護腺癌進展速度較慢,而PSA偵測能力又好,所以建議可採用較長的篩檢間隔,而不須每年都接受重覆篩檢,除了可避免不必要的資源浪費外,也 可減少過度診斷的危險性。目前依據來自歐洲試驗的最佳證據支持採用每四年一次的篩檢策略。

肛門指診(Digital Rectal Examination, DRE)

肛門指診是由醫師經由直腸壁作觸診,以檢查攝護腺是否有硬塊或結節的現象,以早期偵測出攝護腺癌。在PSA問市之前,肛門指診是第一個也是當時唯一能早期 偵測攝護腺癌的篩檢工具。但由於此種方法僅能碰觸到局部的攝護腺,其餘部份若有異常則沒辦法被檢測到,也容易遺漏掉較小的腫瘤病灶,因此肛門指檢的敏感度 並不好,約只有59%( Hoogendam A等人., 1999),而特異度則僅有約77.2%(Mettlin C等人,1991),而對侷限在局部攝護腺的早期攝護腺癌的敏感度則約只有30%,相當的低。再者此項檢查完全仰賴醫師的觸診,很容易受檢查者的觸感及經 驗影響(Smith DS等人,1995)。在PSA問市後,肛門指診已退居為PSA的另一項輔助檢查,不建議單獨仰賴肛門指診。

其他篩檢工具

除了前述目前應用最廣的PSA外,還有許多以PSA為基礎所開發出的相關指標被應用在篩檢或是病 人病情或預後的評估及預測上,包括游離PSA比例(free/total PSA, %free PSA)、PSA變動速率(PSA velocity)及PSA密度(PSA density, PSAD)等,這些臨床指標多用於輔助患者是否應接受攝護腺切片之臨床決策。

篩檢結果異常之處置

對於PSA值異常或是肛門指診異常者,需再進行直腸超音波(Transrectal ultrasound, TRUS)以引導進行系統性切片檢查以進行確診。

過度診斷

雖然透過篩檢可有效找到早期攝護腺癌,並且降低攝護腺癌死亡率,但攝護腺癌篩檢仍有許多爭議與未解決的問題存在,其中尤以過度診斷(over detection)為首。因為攝護腺癌具有相當高的異質性,有些進展速度相當快,具有高威脅性,但有些則進展相當緩慢,甚至於終身不發病,稱為潛在性攝 護性癌(latent prostate cancer)。過去許多對非攝護腺癌患者的屍體解剖研究顯示在從未被診斷為攝護腺癌的死者中,高達26%~46%的50歲以上男性中可在其攝護腺腺體中 找到癌細胞(Breslow等人, 1997; Franks等人, 1954; Carter等人, 1990; Watanabe M 等人, 2000),顯示潛在性攝護性癌在年紀較長的男性中是非常常見的。使用PSA進行篩檢時,除了具有威脅性的攝護腺癌會被診斷出來之外,某一部份的潛在性攝 護腺癌也同時會被診斷出來,此種現象稱作過度診斷,而過度斷又會再造成過度治療,因為目前仍無法有效地將具有威脅性的與無害的潛在性攝護腺癌作區分,所以 易造成無害的潛在性攝護腺癌被診斷出後,又接受一連串不必要的治療,不僅浪費醫療資源,還會因此引發許多不必要的併發症。

此一問題為目前攝護腺癌篩檢最大的挑戰之一。過去許多研究即探討此一問題,結果發現高達18%~84%的篩檢偵測個案都是過度診斷(Zappa M 等人, 1998; McGregor M等人, 1998; Etzioni R等人.,2002; Draisma G等人, 2003; Davidov O 等人, 2004; Ciatto S等人., 2005; Pashayan N等人, 2006; Tsodikov A等人,2006; Telesca D等人, 2008; Yao SL等人, 2003)。近期在芬蘭的研究中也發現每篩檢100位55-67歲男性,將產生3.4位過度診斷的攝護腺癌個案(WU GHM等人, 2012)。許多國家在PSA篩檢問市後亦出現了攝護腺癌發生率大幅上升的現象(Ries LAG等人, 2008),其中過度診斷即在其中扮演了相當重要的角色。

 

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