USPSTF系统综述支持采用CT筛查肺癌

为美国预防服务工作组（USPSTF）进行的一项系统性综述的结果显示，对无症状的肺癌高危成人群体采用低剂量的计算机断层扫描（LDCT）作为筛查手段可降低该病的病死率和全因死亡率，该结果提示这种筛查对大多数患者而言都有明确的收益；基于该结果的指南草案将在线发表于7月30日版的《内科学年鉴》，现可登录USPSTF网站查阅并参与公开评论(2013 July 29 [doi: 10.7326/0003-4819-159-6-201309170-00690])。

俄勒冈州健康与科学大学、波特兰退伍军人事务部医学中心的Linda L. Humphrey医生及其同事指出，2004年，USPSTF认为在推荐采用或不采用LDCT对无症状的成人进行肺癌筛查方面支持证据不足。为此，研究者们对2000年~2013年5月间发表的文献进行了综述，发现4项报告有关对吸烟暴露者进行LDCT筛查的效能结果的试验，试验中同时包括干预组与对照组。3项小型试验显示筛查的收益程度不同，但均无足够的统计学效能；一项大型试验——国家肺筛查试验（NLST）显示，接受筛查的受试者中肺癌病死率下降20%，有统计学意义，全因死亡率下降6.7%。



这项随机的多中心NLST在逾53,000例年龄介于55~74岁的当前吸烟者或至少有30包•年吸烟史的既往吸烟者中比较了每年一次LDCT扫描、持续3年与每年一次单一视图的正位胸部X线片、持续3年的效果（N. Engl. J. Med. 2013;368:1980-91）。结果显示，在每320例完成一次筛查的患者中预防了1例癌症死亡，每219例被筛查的的患者中预防了1例由任何原因导致的死亡；该试验在6.5年的随访后根据结果终止了研究。总体来说，对该群体采用LDCT进行肺癌筛查的收益超过风险。

根据报告危害结局的7项临床试验和13项队列研究的结果，与LDCT有关的危害包括辐射暴露、过度诊断及较高的假阳性结果率，这在大多数情况下可以通过进一步的影像学检查得以确证。6项研究中报告了假阴性结果，发生率为0%~20%不等，但无一项研究评估虚假保证的危害。筛查的收益一定要针对这些潜在的危害进行权衡。

肺癌是美国男性与女性中第三大常见的癌症，但却是癌症相关死亡的第一大原因，占近27%。而且，美国肺癌病例中有大约85%归因于吸烟，而美国人中有将近20%目前仍在吸烟，还有更多的人是既往吸烟者，但这部分人因为有吸烟史，所以仍有较高的患病危险——“肺癌仍将是美国数十年来一个重大的公共卫生问题。”这项综述中纳入的研究都是在根据当前或既往吸烟情况被判定为高危肺癌患者的人群中进行的。不过，肺癌风险较高的患者，其中包括老年人和有肺癌、慢性阻塞性肺病和肺纤维化的家族史者以及存在某些环境或职业暴露者，或许也可以从LDCT筛查中受益。研究者们表示，今后还应该做进一步的研究，以探讨将LDCT筛查集中在最高危肺癌患者中进行的方法，以便于提高良恶性肺部结节的鉴别诊断率，发现侵袭性疾病的早期征象。另外，如果LDCT筛查成为常规检查，就应该衡量危害的风险，并应找到限制危害的方法。

这项综述由卫生保健研究与质量管理局及波特兰退伍军人事务部医学中心资助。Humphrey医生是退伍军人事务部的职员，她和合著者们披露与UpToDate、USPSTF、 AHRQ、退伍军人事务部、美国肺癌学会、胸/LUNGevity基金会、美国国家肺癌伙伴及（或）美国胸科医师协会有密切联系。

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By: SHARON WORCESTER, Internal Medicine News Digital Network

Low-dose computed tomography reduces lung cancer mortality and all-cause mortality when used as a screening tool in asymptomatic adults at high risk for the disease, according to the results of a systematic review conducted for the U.S. Preventive Services Task Force.

In 2004, the USPSTF deemed the evidence insufficient for recommending for or against low-dose computed tomography (LDCT) for lung cancer screening in asymptomatic individuals, but the findings of the current review suggest screening has a definite benefit for most patients, Dr. Linda L. Humphrey, of Oregon Health and Science University and the Portland Veterans Affairs Medical Center, and her colleagues reported.

A draft recommendation based on the findings, published online in the July 30 issue of Annals of Internal Medicine (2013 July 29 [doi: 10.7326/0003-4819-159-6-201309170-00690]), is available on the USPSTF website for public comment.
 
The researchers conducted a review of the literature published between 2000 and May 2013 and identified four trials that reported findings on the efficacy of LDCT screening in patients with smoking exposure for both intervention and control groups. Three small trials showed varying degrees of benefit with screening, but were underpowered; one large trial – the National Lung Screening Trial (NLST) – showed a significant 20% reduction in lung cancer mortality among those screened, as well as a 6.7% reduction in all-cause mortality.

The randomized multicenter NLST compared annual LDCT scans with annual single-view posterior-anterior chest radiographs for 3 years in more than 53,000 current or former smokers aged 55-74 years with at least a 30–pack-year history of smoking (N. Engl. J. Med. 2013;368:1980-91). One cancer death was prevented for every 320 patients who completed one screening, and one death from any cause was prevented for every 219 patients screened in that study; the trial was stopped early after 6.5 years of follow-up based on the findings.

In general, the benefits of LDCT for lung cancer screening in this population outweighed the risks, Dr. Humphrey and her colleagues noted.

Harms associated with LDCT, according to findings from 7 trials and 13 cohort studies that reported on such outcomes, included radiation exposure, overdiagnosis, and a high rate of false-positive findings that were resolved by further imaging in most cases. False negatives were reported in six studies, and the rates ranged from 0% to 20%, but none of the studies evaluated the harm of false reassurance, the investigators noted. The benefits of screening must be weighed against these potential harms.

Lung cancer is the third most common cancer among men and women in the United States, but is the leading cause of cancer-related deaths, accounting for nearly 27%. Furthermore, about 85% of U.S. lung cancer cases are attributable to smoking, and since about 20% of Americans currently smoke – and many more are former smokers who remain at increased risk because of their smoking history – "lung cancer will remain a major public health problem in this country for decades," the investigators wrote.

The studies included in this review were conducted in patients at high risk for lung cancer based on current or former smoking. However, patients at an increased risk for lung cancer, including older adults and those with a family history of lung cancer, chronic obstructive pulmonary disease, pulmonary fibrosis, and certain environmental and occupational exposures, may also benefit from LDCT screening.

"Future research to identify methods for focusing LDCT screening on persons at highest risk for disease, to improve discrimination between benign and malignant pulmonary nodules, and to find early indicators of aggressive disease is warranted," the investigators noted. "If LDCT screening becomes routine, the risk for harms should be measured and methods to limit them should be identified."

The review was funded by grants from the Agency for Healthcare Research and Quality and the Portland Veterans Affairs Medical Center. Dr. Humphrey is employed by the Department of Veterans Affairs, and she and her coauthors disclosed ties with UpToDate, the USPSTF, AHRQ, the Department of Veterans Affairs, the American Lung Association, the Chest/LUNGevity Foundation, the National Lung Cancer Partnership, and/or the American College of Chest Physicians.