前列腺癌使用ADT治療會增加失智風險嗎?


  【24drs.com】雄性素去除療法(Androgen deprivation therapy,ADT)是前列腺癌治療的一個重要部份,但是,一篇新分析認為與失智有關。
  
  這篇觀察型研究發現,ADT使用者的失智發生率比沒有使用者高出2倍以上;5年時發生失智症的絕對增加風險為4.4%,ADT使用者的此一比率為7.9%、非使用者則是3.5% 。
  
  研究結果發表於10月13日JAMA Oncology期刊,不過,在編輯評論中,專家們強調,相關性並不等於因果關係。
  
  今年初,這個團隊報告指出ADT和阿茲海默氏症的關聯,去年,另一組研究者報告指出ADT和神經認知異常的關聯。
  
  費城賓州大學放射腫瘤學家Kevin Nead醫師領導的這篇新研究,使用一個新的文件處理分析方法從原始病歷中收集生化資料。
  
  這篇研究除了發現ADT使用者的失智比率在5年時是未使用者的2倍,對ADT治療時間之分層數據的進一步分析發現,進行至少12個月ADT者的失智絕對增加風險最大(風險比[HR], 2.36;P < .001)。
  
  Nead醫師表示,目前有許多研究認為,雄性素去除療法可能與認知改變有關;此篇研究顯示雄性素去除療法和失智之間有關,支持雄性素去除療法與認知變化之間的關聯。
  
  他表示,這強調了需要採用前瞻型研究進一步分析此一關聯。不過,我們並不會僅僅根據這篇研究就提出改變臨床實務的建議,因為ADT對於某些前列腺癌患者是可以延續生命的療法。
  
  也就是說,Nead醫師強調的重點是,所有前列腺癌患者都應與他們的醫師仔細討論ADT治療之風險與利益。
  
  他解釋,根據現有的文獻資料,與患者針對認知風險進行諮商是合理的,因為在一些回溯與前瞻研究確實有這類發現。醫師與患者在治療期間應持續討論相關的風險與利益,特別是有發生令人困擾的副作用時。
  
  Nead醫師指出,不過,在目前,對於使用ADT的患者,我們並沒有任何證據支持為了負面認知影響進行特定篩檢。
  
  去年發表與阿茲海默氏症的關聯之後,為了這篇研究,Nead 醫師等人將其他類型失智也納入分析。
  
  研究團隊使用一種資訊學方法分析了超過120萬名患者的電子病歷,對前列腺癌男性檢視ADT和隨後發生的失智-包括老年性失智、血管性失智、額顳失智和阿茲海默氏失智之關聯。
  
  他們回顧了史丹佛大學醫學中心在20年間(1994- 2013)的病歷,最後共納入9,272名前列腺癌患者,其中1,826名男性(19.7%)曾使用ADT治療。這些人中,於追蹤中位數3.4年間有314例新發生的失智;失智症診斷的時間中位數是4.0年。
  
  作者們發現,在傾向得分匹配Cox比例風險回歸分析(HR, 2.17;P < .001),以及傳統多變項調整分析(HR, 2.21;P < .001),使用ADT和失智之間有統計上的顯著正相關。
  
  當按使用時間分層時,曾接受ADT至少12個月之患者的失智風險最大(HR, 2.36;P < .001)。隨著ADT使用時間增加,失智風險達到統計上的顯著增加(趨勢P < .001)。
  
  按年齡分層時,曾使用ADT的70歲以下患者,無失智的累計可能性低於同年齡層但未使用ADT者 (log-rank P = .02)。
  
  70歲以上者也有相同模式(log-rank P < .001),作者們並未發現使用ADT與年齡之間有任何相互影響證據 (Wald 0.29;P = .59)。
  
  田納西州納什維爾范德比大學的Colin G. Walsh醫師與Kevin B. Johnson醫師在編輯評論中指出,雖然隨機臨床試驗(RCTs)仍舊是嚴格臨床研究的標準,但是它們執行起來昂貴並且管理複雜。
  
  另一方面,觀察型研究衍生自探勘既有的臨床資料,在許多方面與傳統的RCT不相同。
  
  其一,雖然維護臨床資料庫的成本很大,透過資料探勘進行世代研究所增加的成本僅是RCT成本的一部份。另一方面,相同的處理過程中,一篇資料探勘研究可以促成其他許多分析,分析新世代所需的時間僅是最初心力的一小部份。
  
  Walsh醫師與Johnson醫師寫道,雖然研究招募、納入和排除標準的確定方式與RCT相似,用於識別潛在世代的運算方法實現了前所未有的招募擴展性和速度。
  
  編輯們表示,研究作者將他們的結論正確地架構為需要進一步研究的關聯,且相關性並不等於因果關係這句古諺依舊為真。不過,這類結果已經和RCT一起被納入高階期刊和新聞媒體。
  
  因此,目前的研究代表邁向大規模、低成本、數據驅動型觀察世代研究的另一步,讀者們也必須更加熟悉資料科學應用於生物醫學數據時的統計與技術面向。
  
  資料來源:http://www.24drs.com/
  
  Native link:Does ADT for Prostate Cancer Increase Risk for Dementia?

Does ADT for Prostate Cancer Increase Risk for Dementia?

By Roxanne Nelson, BSN, RN
Medscape Medical News

Androgen deprivation therapy (ADT) is an important component of prostate cancer treatment, but a new analysis suggests an association with dementia.

The observational study found more than twice the incidence of dementia among ADT users compared to nonusers. The absolute increased risk of developing dementia was 4.4% at 5 years, with a rate of 7.9% among ADT users vs 3.5% among nonusers.

The findings were published online October 13 in JAMA Oncology. However, in an accompanying editorial, experts emphasize the old adage that correlation does not mean causation.

Earlier this year, the same team reported a link between ADT and Alzheimer's disease, and last year, another group of researchers reported a link between ADT and neurocognitive dysfunction.

The new study, led by Kevin Nead, MD, DPhil, a radiation oncology resident at the University of Pennsylvania, Philadelphia, used a novel text-processing analytic approach for extracting biomedical data from ordinary patient medical records.

In addition to finding that the rate of dementia was doubled among ADT users compared to nonusers at 5 years, a further analysis that stratified data with respect to the duration of ADT treatment found that patients who had undergone at least 12 months of ADT had the greatest absolute increased risk for dementia (hazard ratio [HR], 2.36; P < .001).

"Multiple studies now suggest that androgen deprivation therapy may be associated with cognitive changes," said Dr Nead. "The current study supports the association between androgen deprivation therapy and cognitive changes by showing an association between androgen deprivation therapy and dementia.

ADT is a life-extending treatment in some men with prostate cancer. Dr Kevin Nead

"This reinforces the need for further evaluation of this association in prospective studies," he told Medscape Medical News. "We would, however, not recommend changes to clinical practice based on this study alone, given that ADT is a life-extending treatment in some men with prostate cancer."

That said, Dr Nead emphasized the importance of all prostate cancer patients having a detailed discussion with their physicians regarding the risks and benefits of ADT.

It would be reasonable to counsel patients regarding potential cognitive risks. Dr Kevin Nead

"Based on the body of literature that now exists, it would be reasonable to counsel patients regarding potential cognitive risks, as this has been shown in multiple retrospective and prospective studies," he explained. "The conversation regarding risks and benefits should continue between patients and their physicians during treatment, particularly if they develop bothersome side effects.

"But we don't, however, have any evidence to support specific screening for negative cognitive effects at this time for men on ADT," Dr Nead added.

Expanding the Focus

After reporting the association with Alzheimer's disease last year, for this study, Dr Nead and colleagues expanded the focus to include other forms of dementia.

Using an informatics approach, the team analyzed electronic medical record data from more than 1.2 million patients to examine the association of ADT with the subsequent development of dementia, including senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer's dementia, among men with prostate cancer.

They reviewed records from the Stanford University Medical Center during a 20-year period (1994 to 2013); the final cohort included 9272 individuals with prostate cancer, of whom 1826 men (19.7%) had been treated with ADT.

Within this group, there were 314 new cases of dementia during a median follow-up of 3.4 years; the median time to dementia diagnosis was 4.0 years.

The authors found that there was a statistically significant positive association between use of ADT and dementia in propensity score–matched Cox proportional hazards regression analysis (HR, 2.17; P < .001) as well as in traditional multivariable adjusted analysis (HR, 2.21; P < .001).

When stratified by duration of use, patients who had been receiving ADT for at least 12 months had the greatest risk for dementia (HR, 2.36; P < .001). There was a statistically significant increased risk for dementia with increasing ADT duration (P < .001 for trend).

In stratification by age, patients younger than 70 years who had received ADT had lower cumulative probability of remaining dementia free in comparison with those in the same age range who did not receive ADT (log-rank P = .02).

The same pattern was true for those older than 70 years (log-rank P < .001). The authors did not observe any evidence of an interaction between use of ADT and age (Wald 0.29; P = .59).

New Style of Trial

In an accompanying editorial, Colin G. Walsh, MD, and Kevin B. Johnson, MD, both from Vanderbilt University, Nashville, Tennessee, note that although randomized clinical trials (RCTs) remain the criterion standard for rigorous clinical investigation, they are expensive to conduct and complex to administer.

"Observational cohort studies derived from mining extant clinical data, on the other hand, have many aspects not shared by traditional RCTs," they write.

One is that although the cost of maintaining a clinical data repository is large, the incremental cost of conducting cohort studies through data mining is a fraction of the cost of an RCT. Another aspect, they note, is that the "same processing that enables 1 data mining study may enable many others. The time required to analyze new cohorts is a fraction of that required for the initial effort.

"Although study recruitment, inclusion, and exclusion criteria are determined in a manner similar to that in an RCT, the algorithmic approach to identifying potential cohorts enables unprecedented scalability and speed of recruitment," write Dr Walsh and Dr Johnson.

The study authors "rightly frame" their conclusions as associations that are in need of further study, and "the adage holds true — correlation does not mean causation," say the editorialists. "However, results such as these have joined RCTs in high-profile journals and the lay press."

Therefore, the current study represents "another step to large-scale, low-cost, data-driven observational cohort studies that will require increased familiarity by readers with the statistical and technical aspects of data science applied to biomedical data," they add.

This study was supported by grants from the National Library of Medicine and the National Institute of General Medical Sciences. Coauthor Nigam Shah, PhD, holds patents related to the use of text-mining methods in clinical data. The other authors and the editorialists have disclosed no relevant financial relationships.

JAMA Oncology. Published online October 13, 2016.

    
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