1.6 Evidence to Support Lung Cancer Screening
1.6.1 The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
1.6.2 The National Lung Screening Trial (NLST)
1.6.3 The Mayo Lung Project
1.6 Lung Cancer Clinical Trials to Support Screening
Prevention of cigarette smoking is likely to have a greater effect in reducing deaths from lung cancer than any screening program. However, lung cancer screening has the potential to reduce the burden of lung cancer, by detecting tumors earlier.
Some early clinical trials used chest X-rays, with and without sputum cytology, to screen males who were at high risk for lung cancer. Some of these studies began in the 1960’s. Some of these key decision-making clinical trials since then include the following:
1.6.1 Lung Cancer Clinical Trials: 1) The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
The Prostate, Lung, Colorectal, and Ovarian (PLCO) trial was a large (154,942 patient), randomized clinical trial using a single-view posterior-anterior chest X-ray. Screening for lung cancer consisted of a single posterior-anterior (PA) chest X-ray performed at baseline and annually for three years. Lung cancer incidence was higher in individuals who had prior or current smoking exposure, but there was no difference in the incidence of lung cancer or in mortality among smokers who were in the screening or control groups. Approximately 20 % of lung cancers in the screening group were detected by screening. In the PLCO study, annual screening with chest X-ray, compared with ‘usual care,’ did not reduce lung cancer mortality.
For full details and information on the PLCO trial click here.
1.6.2 Lung Cancer Clinical Trials 2) The National Lung Screening Trial (NLST)
The National Lung Screening Trial (NLST) is a randomized trial conducted by the National Cancer Institute (NCI). NLST compared annual screening using low-dose chest CT (LDCT) scanning with chest X-ray for three years in more than 53,000 high-risk individuals and from 33 medical centers within the U.S.
‘High-risk’ individual criteria for participation in the NLST were:
- age between 55 to 74 years;
- a history of smoking of at least 30 pack-years and,
- if a former smoker, having given up smoking within the previous 15 years.
NLST demonstrated a decrease in the occurrence of lung cancer and from mortality from all other causes, with a median follow-up being 6.5 years. There were 645 cases of lung cancer per 100,000 person years (1060 cancers) in the LDCT group. There were 572 cases of lung cancer per 100,000 person years (941 cancers) in the chest X-ray group. There were 247 cases of lung cancer per 100,000 person-years in the CT group. There were 309 lung cancer deaths in the X-ray group, giving a relative mortality reduction of 20 % and an absolute reduction of 62 lung cancer deaths per 100,000 person-years. In the LDCT group, there was a 6.7 % relative reduction in mortality from all causes and an absolute reduction of 74 deaths per 100,000 person-years.
In the National Lung Screening Trial (NLST), the overall average effective dose of low-dose CT was 2 mSv; this compared with 7 mSv for a standard, diagnostic chest CT.
This study found that the rate of lung cancer detection did not diminish between screening years; this suggested that ongoing screening would be necessary. In the second and third screening rounds, fewer stage IV (advanced / metastatic) lung cancers were detected in the LDCT group than the chest X-ray group.
The lung cancers detected by screening in the NLST were mostly stage I or II tumors (70 % of CT-detected and 56.7 % of X-ray detected); small cell lung cancers were < 10 % of detected cancers. Chest LDCT identified mainly adenocarcinomas of the lung.
A systematic review, in 2012, of the outcomes of lung cancer screening with low-dose CT, identified the NLST as the only trial with data that could allow a mortality benefit to be concluded. Other trials were either too small, too preliminary or had study design flaws that precluded interpretation (Bach et al, 2012). In 2013, analysis of another systematic review supported the data from the NLST study (Humphrey et al, 2013). For more information on reduced mortality rates click here.
1.6.3 Lung Cancer Clinical Trials 3) The Mayo Lung Project
In 1984, the Mayo Lung Project was the first North American trial to assess the value of lung cancer screening that used chest X-ray and sputum cytology as first-stage tests. The study included 10,993 male smokers. Following screening, they were all randomly assigned to a six-year program of 4-monthly chest X-ray and sputum cytology, or to a control group receiving usual care who were advised to have an annual chest X-ray.
Initial screening identified 91 lung cancers (0.8 %). After six years, 206 new lung cancers were diagnosed in the screening population and 160 cancers were diagnosed in the control group. More early-stage lung cancers were diagnosed in the screened group, but there was no reduction in late-stage tumors. Twenty years of follow-up showed that death rates for lung cancer were higher in the screened group (4.4 versus 3.9 deaths per 1,000 patient-years).
The study and its analysis has been criticised for the following reasons: half of the control group had a ‘screening’ chest X-ray during the study; patient compliance in the intervention group was only 75 % and no group was completely unscreened. It is important to know the limitations of this study as its conclusion was that there was no reduction in mortality when using chest X-ray alone or chest X-ray with sputum cytology.
For more information on the Mayo Clinic Experience, click here.
Gohagan J, Marcus P, Fagerstrom R, et al.(2004). Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the Lung Screening Study of the National Cancer Institute. Chest. 126(1):114–21. (Retrieved 22nd Jan 2015): http://journal.publications.chestnet.org/article.aspx?articleid=1082627
Fontana RS, Sanderson DR, Taylor WF, Woolner LB. et al. (1984) Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Europe Pubmed Central 130(4):561-565 (Retrieved 31st March 2015): http://europepmc.org/abstract/med/6091507
Center for Disease Control and Prevention (CDC) What Screening Tests Are There? (Retrieved 22nd Jan 2015): http://www.cdc.gov/cancer/lung/basic_info/screening.htm
National Cancer Institute National Lung Screening Trial: Questions and Answers (Retrieved 1st April 2015): http://www.cancer.gov/newscenter/qa/2002/nlstqaQA