LUNG CANCER SCREENING

Background:

Lung cancer facts

In the U.S., lung cancer is the leading cause of cancer death
Lung cancer has a five-year survival rate of 16.8%, one of the poorest survival rates among cancers
Five-year survival is much better when the cancer is diagnosed while still localized (52%). The majority of patients are diagnosed after the cancer has metastasized. [1]
It is estimated that 85% of lung cancers are attributable to smoking
In the U.S., there are an estimated 94 million current or former smokers [2]
The cumulative risk of death from lung cancer by age 75 in a lifetime smoker has been estimated to be 16% in men and 9.5% in women (based on data from 1990) [3]

Lung cancer screening: A number of organizations now recommend lung cancer screening with low-dose CT scans in heavy smokers who meet certain criteria (see lung cancer screening recommendations). In the past, annual chest X-rays have been studied as a screening tool for lung cancer. Chest X-ray screening has not been found to decrease lung cancer mortality. In 2011, results from the National Lung Screening Trial (NLST) were published. The NLST was an enormous, randomized controlled trial (53,454 subjects) that compared annual screening with low-dose CT scan to annual screening with chest X-ray in heavy smokers. The trial showed that low-dose CT scan screening reduced lung cancer mortality and overall mortality compared to chest X-ray screening. Since the publication of the NLST trial, the American Cancer Society, the American Lung Association, the National Comprehensive Cancer Network, the American College of Chest Physicians, and the USPSTF have all made recommendations in favor of lung cancer screening based on the NLST results.

NLST - Annual Low-Dose CT Scan vs Annual Chest X-Ray for Lung Cancer Mortality in Heavy Smokers, NEJM (2011) [Pubmed Abstract]

The NLST enrolled 53,454 smokers

Main inclusion criteria

Age between 55 - 74 years
Smoking history ≥ 30 pack-years
If former smoker, quit within the last 15 years

Main exclusion criteria

History of lung cancer
Hemoptysis
Unexplained weight loss

Baseline characteristics

Average age 61.4 years
Male sex - 59%
Median cigarette history - 48 pack-years
Median duration of smoking - 43 years
Current smoker - 48%

Randomized treatment groups

Group 1 (26,722 patients) - Annual lung cancer screening with low-dose CT scan
Group 2 (26,732 patients) - Annual chest X-ray

Primary outcome: Death from lung cancer

Results

Outcome	CT scan	Chest X-ray	Comparisons
Duration: Median of 6.5 years
Primary outcome	1.33%	1.66%	p=0.004
Overall mortality	7.02%	7.48%	p=0.02
Lung cancer diagnosis	3.96%	3.52%	p>0.05
False-positive rate	96.4%	94.5%	N/A
Adherence	95%	93%	N/A
In the CT scan group, 39% of participants had at least one positive screening test. In the chest X-ray group, 16% of participants had at least one positive screening test.

Findings: Screening with the use of low-dose CT reduces mortality from lung cancer

Summary:

In the NLST, annual low-dose CT scan reduced the absolute risk of lung cancer mortality by 0.33% over a median of 6.5 years when compared to annual chest X-ray. Overall mortality was reduced by 0.46%. The enormous size of the trial made these marginal differences significant.
The false-positive rate for CT scans was 96.4%. This means the test has almost no positive predictive value.
Studies comparing CT scan to no screening are ongoing in Europe. Interim results from several of these trials have found no mortality benefit [PMID 26485620, PMID 19520905]
In conclusion, low-dose CT scanning for lung cancer offers a very marginal benefit in patients with a very heavy smoking history. About 40% of patients can expect to have a positive screening test which will likely lead to more testing. Of those with a positive test, only 0.6% will actually have lung cancer. This raises questions about the cost-effectiveness and overall benefit of this screening.

Bibliography
1 - ACS GL
2 - JAMA review - PMID 23512063
3 - BMJ study - PMID 10926586
4 - NLST study PubMed Abstract