Lung cancer screening


Lung cancer screening refers to cancer screening strategies used to identify early lung cancers before they cause symptoms, at a point where they are more likely to be curable. More than 224,000 new cases of lung cancer are expected in the United States in 2016 with approximately 155,000 deaths expected in 2017. 57% were diagnosed in advanced stages where survival is poor. Screening research addresses potential differences in multiple parameters between groups of research subjects with and without screening. Because there is a substantially higher probability of long-term survival following treatment in localized than in advanced stage, the specific rationale of lung cancer screening is to diagnose the disease in stage I. Research parameters include population cancer-specific mortality, all-cause mortality, long-term survival following diagnosis of cancer, risks of screening and cost-effectiveness. Screening studies for lung cancer have only been done in high risk populations in the U.S., such as smokers and workers with occupational exposure to certain substances. Results from large randomized studies have recently prompted a large number of professional organizations and governmental agencies in the U.S. to now recommend lung cancer screening in select populations.
CT screening has been associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there have been as many as 19 falsely positives scans. When screening is done in the context of a process of diagnostic tests, false positives have been reduced to approximately 12%. Other concerns include radiation exposure and the cost of testing along with the follow up of tests. Research has not found two other clinically available tests – sputum cytology or chest radiograph screening tests — to reduce the overall number of people who die from lung cancer.
Screening studies for lung cancer have only been done in high risk populations in the U.S., such as smokers and workers with occupational exposure to certain substances. In the 2010s recommendations by medical authorities are turning in favour of lung cancer screening, which is likely to become more widely available in the advanced economies. Currently multiple professional organizations as well as the United States Preventive Services Task Force and the Centers for Medicare and Medicaid Services concur and endorse low-dose, computerized tomographic screening for individuals at high-risk of lung cancer.

Risks of Screening

Research has found that regular early screening with two other clinically available tests – sputum cytology and chest radiograph — does not have an overall benefit. There is evidence suggesting that regular screening of high-risk smokers and former smokers may reduce the mortality in this particular group of people. More research is necessary to determine the relative risks and benefits for the general public and people who have a low risk of lung cancer.
CT screening has been associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there have been as many as 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with the follow up of tests. False reassurance from false negative findings, overdiagnosis, short term anxiety/distress, and increased rate of incidental findings are other risks. It has been estimated that radiation exposure from repeated screening studies could induce cancer formation in a small percentage of screened subjects, so this risk should be mitigated by a high prevalence of lung cancer in the population being screened.

Guidelines

The National Lung Screening Trial found that screening people who were between 55 and 74 years who had smoked for a long time, and had quit smoking no more than 15 prior to being screened, allows timely intervention to the extent that 16% fewer people died from lung cancer, compared to people who were not screened.
Based on this study, the U.S. Preventive Services Task Force recommends annual screening for lung cancer with low-dose computed tomography in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3%.
The definition of those considered to be at sufficiently high risk to benefit from screening varies according to different guidelines. Initially high-risk included people age 55–74 who have smoked a pack of cigarettes daily for 30 years including time within the past 15 years. The United States Preventative Services Task Force and Centers for Medicare and Medicaid Services categorizations are for those age 55–80 and 55-77 respectively who have smoked an average of a pack of cigarettes daily for 30 years and are current smokers or have quit within the past 15 years.
The National Comprehensive Cancer Network guideline recommends screening in a second risk category that includes individuals over age 50 who have smoked more than 20 pack years who have a second risk factor and sets no upper age limit at which screening should be terminated.

History

Studies have explored various methods of screening, including breath tests and blood tests to detect for lung cancer. While there is scientific evidence that lung cancer is detectable with high sensitivity and more than 90% specificity in the human breath, no screening test has been clinically validated to be useful to be applied in screening.
Medical imaging has been extensively studied. Lung cancer screening programs that utilize plain chest X-rays and sputum analysis programs have generally not been found effective in reducing mortality from lung cancer, except in high-risk smokers. A cost-benefit versus potential harm analysis from screening people with different risks of lung cancer has not been fully investigated.
The Mayo Lung Project followed over 9000 male smokers over 45 years of age who smoked one or more packs a day from 1971 to 1986 and compared intensive CXR and sputum screening every three times per year compared to less frequent annual screening. The results showed that more frequent screening resulted in higher resectability rate, but made no difference in mortality from lung cancer. CXR screening were found to detect 6 times as many new cancers as sputum tests.
In 1996 results were published of a study of around 6,800 subjects screened in Japan; 67% to 73% of CT-detected lung cancers were missed by chest x-ray, the same test used in the comparison group of some randomized controlled trials of lung cancer screening.
The National Lung Screening Trial was a United States-based clinical trial which recruited research participants between 2002–2004. It was sponsored by the National Cancer Institute and conducted by the American College of Radiology Imaging Network and the Lung Screening Study Group. The major research in the trial was to compare the efficacy of low-dose helical computed tomography and standard chest X-ray as methods of lung cancer screening.
Results of CT screening on over 31,000 high-risk patients published in late 2006 in the New England Journal of Medicine. In this study, 85% of the 484 detected lung cancers were stage I and thus highly treatable. Historically, such stage I patients would have an expected 10-year survival of 88%. Critics of the I-ELCAP study point out that there was no randomization of patients and the patients were not actually followed out to 10 years post detection.
In contrast, a March 2007 study in the Journal of the American Medical Association found no mortality benefit from CT-based lung cancer screening. 3,200 current or former smokers were screened for 4 years and offered 3 or 4 CT scans. Lung cancer diagnoses were 3 times as high, and surgeries were 10 times as high, as predicted by a model, but there were no significant differences between observed and expected numbers of advanced cancers or deaths. Additional controversy arose after a 2008 New York Times reported that the 2006, pro-CT scan study in the New England Journal of Medicine had been funded indirectly by the parent company of the Liggett Group, a tobacco company.
In 2011 the National Lung Screening Trial found that CT screening offers benefits over other screenings. This study was recognized for providing supporting evidence for using CR screening to screen for lung cancer and for encouraging others to reflect on the merits and drawbacks of other types of screening. Research has not shown that two other available tests – sputum cytology or chest radiograph screening tests — have any benefit.
The trial led to a recommendation in the United States that CT screening be used on people at high risk for developing lung cancer in an effort to detect the cancer earlier and reduce mortality.
In December 2013 the U.S. Preventive Services Task Force changed its long-standing recommendation that there is insufficient evidence to recommend for or against screening for lung cancer to the following: "The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults ages 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. These recommendations were used by the Agency for Healthcare Research and Quality to produce to support informed decision making for lung cancer screening. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery". Another U.S. guideline recommendation is very similar, but with a cut-off at age 74. The English National Health Service was in 2014 re-examining the evidence for screening.

Development of guidelines

s previously issued by the American College of Chest Physicians in 2007 recommended against routine screening for lung cancer because of a lack of evidence that such screening was effective. The newest ACCP guidelines take into account findings from the National Lung Screening Trial and state: "For smokers and former smokers who are age 55 to 74 and who have smoked for 30 pack-years or more and either continue to smoke or have quit within the past 15 years, we suggest that annual screening with low-dose CT should be offered over both annual screening with CXR or no screening, but only in settings that can deliver the comprehensive care provided to National Lung Screening Trial participants ".
Following the National Cancer Institute's National Lung Screening Trial, guidelines were released initially in 2012 by the National Comprehensive Cancer Network, an alliance of twenty one cancer centers in the United States. Their consensus guidelines, which are updated annually, support screening as a process, not a single test, and discuss risks and benefits of screening in high risk individuals within a comprehensive multidisciplinary program. Screening is only recommended for individuals defined as high risk meeting specific criteria. More details can be found in their patient guidelines. While lung cancer screening programs have been supported by the NCCN, International Association for the Study of Lung Cancer, American Cancer Society, The American Society of Clinical Oncology, and other organizations, the costs of screening may not be covered by medical insurance policies, unless the eligibility criteria specified by the Centers for Medicare and Medicaid Services are met.
As of 2017 usage of lung cancer screening in the U.S. after Medicare agreed to pay for screening and after guidelines were published was low, with the most uptake in the Midwest. In 2017 a task force published a review of evidence and recommendations for advancing implementation.