LUNG CANCER SCREENING REVIEW -
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.
- 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. 
- 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 
- 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) 
- The NLST study randomized 53,454 smokers to annual lung cancer screening with low-dose CT scan (26,722 smokers) or chest X-ray (26,732 smokers) for 3 years
- The inclusion criteria for the trial are important because subsequent guidelines have used these same criteria in their screening guidelines
- Inclusion criteria for the study:
- Age between 55 - 74
- Smoking history of at least 30 pack-years (1 pack-year = smoking a pack of cigarettes every day for one year; 2 pack-years = smoking 2 packs a day for one year, and so on)
- If a participant was a former smoker, they had to have quit within the last 15 years
- PRIMARY OUTCOME: Death from lung cancer
- After a median follow-up of 6.5 years, the following was seen:
- The low-dose CT group had significantly fewer lung cancer deaths than the chest x-ray group (1.33% vs 1.66%, absolute risk reduction 0.33%, relative risk reduction 20%, p=0.004)
- The low-dose CT group had significantly lower overall mortality than the chest x-ray group (7.02% vs 7.48%, absolute risk reduction 0.46%, relative risk reduction 6.7%, p=0.02)
- Adherence rates in both groups were very high, 95% in CT scan group and 93% in chest X-ray group 
Other important findings:
- Positive screening rates were high: CT scan group - 39% of participants had at least one positive screening CT scan; Chest X-ray group - 16% of participants had at least one
positive screening chest X-ray
- False-positive screening rates were very high: CT scan group - 96.4% false-positive rate; Chest X-ray group: 94.5% false-positive rate 
StraightHealthcare analysis: Results from the NLST study have persuaded a number of organizations to endorse lung cancer screening in heavy smokers. In our
opinion, there are a number of limitations to the NLST study that need to be considered.
- The absolute risk reduction for lung cancer mortality was only 0.33% (for overall mortality - 0.46%). If the study had not been so large, this effect size would not have been
significant. The large sample size needed to obtain a significant result raises the question as to whether the intervention is clinically significant and cost-effective.
- The false-positive rate for people with a positive CT scan was 96.4%. This means the test has almost no positive predictive value.
- Patients were screened for 3 years. The optimal length of screening is unknown. Some of the new recommendations (ex. American Cancer Society) recommend that patients receive annual
low-dose CT screening up to age 74. This recommendation seems excessive since the adverse effects of annual CT scan radiation are unknown, and the risk of overdiagnosis will most definitely
increase with each subsequent scan, particularly in this population that has a higher risk of mortality from a number of other diseases (ex. heart disease, head and neck cancers, etc.)
- Given the high number of false-positive results, patients who undergo screening will be subjected to numerous repeat scans and other procedures that are unnecessary. An observational study
that looked at real world implementation of the guideline in select VA hospitals found that the false-positive rate for CT screening was 97.4%.
- Studies comparing CT scan to no screening are ongoing in Europe. Interim results from several of these trials have found no mortality benefit
(see Danish Lung Cancer Trial, DANTE trial)
- The inclusion criteria for the study included only very heavy smokers. Even in this very high-risk group, there was only a 0.33% absolute risk reduction for lung cancer mortality. In practice,
many patients who do not meet the criteria will still want to be screened. Based on the available evidence, it's unlikely they will benefit.
CONCLUSION: The benefit of low-dose CT screening for lung cancer is marginal. Based on the available evidence, its unclear if it's worth the costs, risks, anxiety, and resource utilization.
1 - ACS GL
2 - JAMA review - PMID 23512063
3 - BMJ study - PMID 10926586
4 - NLST study PubMed Abstract