Lung cancer screening

Computed tomography (CT) scanner, the usually recommended screening technique

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. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. Results from large randomized studies have recently prompted medical authorities to reverse their previous position and now recommend lung cancer screening in select populations.

For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life.^[1] This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%).^[2][3] High risk people are those age 55–74 who have smoked a pack of cigarettes daily for 30 years including time within the past 15 years.^[1]

CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment.^[4] For each true positive scan there are more than 19 falsely positives scans.^[5] Other concerns include radiation exposure^[4] and the cost of testing along with the follow up of tests.^[1] Research has not found two other clinically available tests – sputum cytology or chest radiograph (CXR) screening tests — to have any benefit.^[6]

Screening studies for lung cancer have only been done in high risk populations, 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. In December 2013 the U.S. Preventive Services Task Force (USPSTF) 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 (AHRQ) to produce patient and clinician resources 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".^[7] Another U.S. guideline recommendation is very similar, but with a cut-off at age 74.^[1] The English National Health Service was in 2014 re-examining the evidence for screening.^[8]

Risks of Screening

CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment.^[1] For each true positive scan there are more than 19 falsely positives scans.^[5] Other concerns include radiation exposure and the cost of testing along with the follow up of tests.^[1] False reassurance from false negative findings, overdiagnosis, short term anxiety/distress, and increased rate of incidental findings are other risks.^[9] Radiation exposure from repeated screening studies could actually induce cancer formation in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened.^[1]

Research has not found two other clinically available tests – sputum cytology or chest radiograph (CXR) screening tests — to have any benefit.^[6] However, there is scientific evidence that lung cancer may be detectable in the breath of patients.^[10]

History

The National Lung Screening Trial was a United States-based clinical trial which recruited research participants between 2002–2004.^[11] It was sponsored by the National Cancer Institute and conducted by the American College of Radiology Imaging Network and the Lung Screening Study Group.^[11] The major research in the trial was to compare the efficacy of low-dose helical computed tomography (CT screening) and standard chest X-ray as methods of lung cancer screening.^[12]

In 2011 the National Lung Screening Trial found that CT screening offers benefits over other screenings.^[13] 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.^[4] Research has not shown that two other available tests – sputum cytology or chest radiograph (CXR) screening tests — have any benefit.^[6]

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.^[4]

Other CT studies

The International Early Lung Cancer Action Project (I-ELCAP) published the results of CT screening on over 31,000 high-risk patients in late 2006 in the New England Journal of Medicine.^[14] 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 (all received CT scans and there was no comparison group receiving only chest x-rays) and the patients were not actually followed out to 10 years post detection (the median followup was 40 months). Regardless of these shortcomings, it is generally recognized that the prognosis of lung cancer decreases dramatically when the disease is in late stage,^[15][16] and that CT screening for lung cancer allows detection of lung cancer during its earliest, most curable stage. CT screening for lung cancer has already been extensively compared to chest x-ray screening in Japan. Among over 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.^[17][18][19]

In contrast, a March 2007 study in the Journal of the American Medical Association (JAMA) found no mortality benefit from CT-based lung cancer screening.^[20] 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.^[21] 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.^[22]

Other clinically established testing methods not found to show benefit

Lung cancer screening programs that utilize plain chest x-rays (CXR) and sputum analysis programs have generally not been found effective in reducing mortality from lung cancer.^[23] The Mayo Lung Project, followed over 9000 male smokers over 45 years of age who smoked 1+ packs/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 (more early-stage detection), but made no difference in mortality from lung cancer. CXR screening were found to detect 6 times as many new cancers as sputum tests.^[24]

Studies have explored other means of testing including breath tests and blood test to detect for lung cancer. While there is scientific evidence that lung cancer is detectable with high sensivity and more than 90% specifity in the human breath, no screening test has been clinically validated to be useful to be applied in screening.^[25][26][27]

Developing guidelines

Clinical practice guidelines 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.^[28] 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 (LDCT) 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 (Grade 2B)".^[29]

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 regularly updated, 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.^[30] While lung cancer screening programs have been supported by the NCCN,^[31] International Association for the Study of Lung Cancer (IASLC),^[32] American Cancer Society,^[33] The American Society of Clinical Oncology (ASCO),^[34] and other organizations, the costs of screening may not be covered by medical insurance policies.

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