前列腺癌使用ADT治疗会增加失智风险吗?


  【24drs.com】雄性素去除疗法(Androgen deprivation therapy,ADT)是前列腺癌治疗的一个重要部份,但是,一篇新分析认为与失智有关。
  
  这篇观察型研究发现,ADT使用者的失智发生率比没有使用者高出2倍以上;5年时发生失智症的绝对增加风险为4.4%,ADT使用者的此一比率为7.9%、非使用者则是3.5% 。
  
  研究结果发表于10月13日JAMA Oncology期刊,不过,在编辑评论中,专家们强调,相关性并不等于因果关系。
  
  今年初,这个团队报告指出ADT和阿兹海默氏症的关联,去年,另一组研究者报告指出ADT和神经认知异常的关联。
  
  费城宾州大学放射肿瘤学家Kevin Nead医师领导的这篇新研究,使用一个新的文件处理分析方法从原始病历中收集生化资料。
  
  这篇研究除了发现ADT使用者的失智比率在5年时是未使用者的2倍,对ADT治疗时间之分层数据的进一步分析发现,进行至少12个月ADT者的失智绝对增加风险最大(风险比[HR], 2.36;P < .001)。
  
  Nead医师表示,目前有许多研究认为,雄性素去除疗法可能与认知改变有关;此篇研究显示雄性素去除疗法和失智之间有关,支持雄性素去除疗法与认知变化之间的关联。
  
  他表示,这强调了需要采用前瞻型研究进一步分析此一关联。不过,我们并不会仅仅根据这篇研究就提出改变临床实务的建议,因为ADT对于某些前列腺癌患者是可以延续生命的疗法。
  
  也就是说,Nead医师强调的重点是,所有前列腺癌患者都应与他们的医师仔细讨论ADT治疗之风险与利益。
  
  他解释,根据现有的文献资料,与患者针对认知风险进行谘商是合理的,因为在一些回溯与前瞻研究确实有这类发现。医师与患者在治疗期间应持续讨论相关的风险与利益,特别是有发生令人困扰的副作用时。
  
  Nead医师指出,不过,在目前,对于使用ADT的患者,我们并没有任何证据支持为了负面认知影响进行特定筛检。
  
  去年发表与阿兹海默氏症的关联之后,为了这篇研究,Nead 医师等人将其它类型失智也纳入分析。
  
  研究团队使用一种信息学方法分析了超过120万名患者的电子病历,对前列腺癌男性检视ADT和随后发生的失智-包括老年性失智、血管性失智、额颞失智和阿兹海默氏失智之关联。
  
  他们回顾了史丹佛大学医学中心在20年间(1994- 2013)的病历,最后共纳入9,272名前列腺癌患者,其中1,826名男性(19.7%)曾使用ADT治疗。这些人中,于追踪中位数3.4年间有314例新发生的失智;失智症诊断的时间中位数是4.0年。
  
  作者们发现,在倾向得分匹配Cox比例风险回归分析(HR, 2.17;P < .001),以及传统多变项调整分析(HR, 2.21;P < .001),使用ADT和失智之间有统计上的显著正相关。
  
  当按使用时间分层时,曾接受ADT至少12个月之患者的失智风险最大(HR, 2.36;P < .001)。随著ADT使用时间增加,失智风险达到统计上的显著增加(趋势P < .001)。
  
  按年龄分层时,曾使用ADT的70岁以下患者,无失智的累计可能性低于同年龄层但未使用ADT者 (log-rank P = .02)。
  
  70岁以上者也有相同模式(log-rank P < .001),作者们并未发现使用ADT与年龄之间有任何相互影响证据 (Wald 0.29;P = .59)。
  
  田纳西州纳什维尔范德比大学的Colin G. Walsh医师与Kevin B. Johnson医师在编辑评论中指出,虽然随机临床试验(RCTs)仍旧是严格临床研究的标准,但是它们执行起来昂贵并且管理复杂。
  
  另一方面,观察型研究衍生自探勘既有的临床资料,在许多方面与传统的RCT不相同。
  
  其一,虽然维护临床资料库的成本很大,透过资料探勘进行世代研究所增加的成本仅是RCT成本的一部份。另一方面,相同的处理过程中,一篇资料探勘研究可以促成其它许多分析,分析新世代所需的时间仅是最初心力的一小部份。
  
  Walsh医师与Johnson医师写道,虽然研究招募、纳入和排除标准的确定方式与RCT相似,用于识别潜在世代的运算方法实现了前所未有的招募扩展性和速度。
  
  编辑们表示,研究作者将他们的结论正确地架构为需要进一步研究的关联,且相关性并不等于因果关系这句古谚依旧为真。不过,这类结果已经和RCT一起被纳入高阶期刊和新闻媒体。
  
  因此,目前的研究代表迈向大规模、低成本、数据驱动型观察世代研究的另一步,读者们也必须更加熟悉资料科学应用于生物医学数据时的统计与技术面向。
  
  资料来源: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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