高危吸烟者应每年接受CT肺癌筛查

旧金山(EGMN)—— 根据5月20日在线发表在《JAMA》杂志上的一篇系统综述，年龄55~74、有≥30包-年吸烟史者，即使已在15年内戒烟，也应每年接受小剂量CT肺癌筛查。

这篇综述构成了美国胸科医师协会(ACCP)和美国临床肿瘤学会(ASCO)新肺癌筛查临床实践指南的基础。这两部指南的建议在很大程度上基于纳入53,454例患者的随机NLST，该试验显示在每1,000例高危吸烟者中，3轮年度CT筛查可在7年内挽救约3人的生命，这一结果至少与老年女性接受乳腺X线筛查的绝对收益具有可比性（N. Engl. J. Med. 2011;365:395-409）。

应当在为患者提供筛查选择之前告知其风险(包括误诊和不必要手术)和潜在益处。共同作者、南加州Kaiser 医疗集团健康服务研究部副主任Michael K. Gould博士指出：“人们应该知道，每20个阳性结果里就有19个是假阳性。筛查阳性并不等于诊断肺癌。”而且根据指南，CT筛查不适用于非高危的既往吸烟者和目前吸烟者，也不可用于因有严重合并症而预期寿命较短或不能接受治疗的患者(JAMA 2012 May 20 [doi:10.1001/jama.2012.5521])。

主要作者、纪念Sloan-Kettering癌症中心的Peter Bach博士指出，对于这些患者，筛查的风险和收益“难分伯仲”。

经过广泛的文献回顾，研究者在最终分析中纳入了8项随机试验和13项队列研究。虽然他们坚信筛查对高危患者有益——主要基于NLST，以及一些较小的试验——但也对筛查潜在危害的数据缺乏不无担心，因此仅建议对高危患者进行筛查。总体而言，由于缺乏进一步研究，两部指南的建议根据GRADE系统均被定性为“弱”。

高危患者接受筛查对戒烟、生活质量和成本效益比的影响确实很不明确，“我们完全不确定筛查的频率和持续时间”。另外同样不清楚的是，在标准较松的非大学附属医院开展肺癌筛查会是怎样的情况。在大学附属医院中，患者对筛查的依从性为90%，不良事件罕见，而且可提供后续的诊断和干预。为了减弱这一问题的影响，指南建议在相似的多学科综合诊疗中心开展筛查。

作者还呼吁建立筛查登记，“记录每例患者的经历以帮助帮助我们建立一个类似乳腺X线筛查的质量评估系统，从而使筛查收益最大化、损害最小化”。

由于还存在很多未知数，编辑Howard Bauchner博士称《JAMA》杂志内部有大量争论。 “我们反复讨论筛查是否弊大于利的问题。最后，杂志选择发表这篇综述，因为美国每年有160,000人死于肺癌，而过去10年间几乎没有取得进展。这是我们第一次有希望改变这些数据。”

这篇文章的附件中包含一个名为“就CT筛查进行交谈”的章节，介绍了如何与患者讨论这一问题。

美国胸科学会(ATS)已认可了这两部指南。

Bach博士报告称接受了由基因泰克公司提供的演讲费。共同作者报告与多家药企和政府部门有联系。Gould博士和Bauchner博士报告称无相关利益冲突。

BY M. ALEXANDER OTTO
Elsevier Global Medical News

SAN FRANCISCO (EGMN) – Patients aged 55-74 years who have at least a 30 pack-year smoking history should be offered annual low-dose CT lung cancer screening, even if they have quit within the past 15 years, according to a systematic review published online May 20 in JAMA.

The review forms the basis of the new lung cancer screening clinical practice guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology. The recommendations are based largely on the 53,454-patient, randomized NLST (National Lung Screening Trial), which found that for every 1,000 high-risk smokers, three rounds of annual CT screening saved approximately three lives over about 7 years, which is comparable, at least, to the absolute benefit of screening mammographies in older women (N. Engl. J. Med. 2011;365:395-409).

The risks – including misdiagnosis and unnecessary surgery – and potential benefits should be explained to patients before they opt for screening. “People need to know” that “19 out of 20 positive results are going to be false positive. A positive screen does not equal a diagnosis of lung cancer,” said coauthor Dr. Michael K. Gould, assistant director for health services research at Kaiser Permanente of Southern California, Pasadena.

In addition, “CT screening should not be performed” in smokers and ex-smokers who fall outside of the high-risk group, or in those with severe comorbidities that limit life expectancy or preclude treatment, according to the guidelines (JAMA 2012 May 20 [doi:10.1001/jama.2012.5521]).

The risks and benefits of screening are just “too close to call” for those patients, said lead author Dr. Peter Bach, director of the center for health policy and outcomes at Memorial Sloan-Kettering Cancer Center in New York.

After an extensive literature review, the researchers included eight randomized trials and 13 cohort studies in its final analysis. Although they are confident that screening benefits high-risk patients – based mostly on the NLST, with some added input from smaller trials – they are also concerned about the lack of data on the potential harms of screening, which led to the recommendation to offer screening only to high-risk patients, Dr. Bach said.

Overall, the lack of additional research led both recommendations to be characterized as “weak” under the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

The impact of screening even high-risk patients “on smoking cessation, quality of life, and cost-effectiveness is really quite unclear. We don’t know in any sense what the frequency should be or the duration,” Dr. Bach said.

Also unclear is how screening will play out in settings less rigorous than the academic centers where the NLST was conducted. Patient compliance with screening at those centers was 90%, adverse events were rare, and subsequent diagnostic work-ups and interventions were available.

To mitigate potential problems, the guidelines recommend that screening be done in similar multidisciplinary settings.

The authors also call for a screening registry “that records each patient’s experience [to] help us develop a quality measurement system similar to mammography screening that could maximize the benefits and minimize the harm for individuals who undergo screening,” Dr. Bach said.

Given the unknowns, there was a lot of debate at JAMA about whether to publish the review, said editor Dr. Howard Bauchner.

“There were many discussions about [if it] would do more harm than good.” In the end, the journal opted to publish because 160,000 “people die of lung cancer each year” in the United States, with “little progress over the last decade. This is the first hope we have that we can impact those data,” he said.

A supplement to the JAMA article includes a section entitled “Components of a Conversation About CT Screening,” which addresses how to talk with patients about these issues.

The American Thoracic Society has endorsed the guidelines.

Dr. Bach reported that he has received speaking fees from Genentech. Coauthors reported ties to pharmaceutical companies such as Oncimmune and governmental agencies such as the U.S. National Cancer Institute. Dr. Gould and Dr. Bauchner said they have no relevant disclosures.