Lung cancer screening
Encyclopedia
Lung cancer screening refers to strategies used to identify early lung cancer
s before they cause symptoms, at a point where they are more likely to be curable. Screening
refers to the use of medical tests to detect disease in asymptomatic people. Screening studies have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because 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.
in 2007 recommended against routine screening for lung cancer because of a lack of evidence that such screening was effective.
In 2004, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) gave a grade I recommendation indicating that "the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer".
examination programs were not effective in reducing mortality from lung cancer. Previous studies (Mayo Lung Project and Czechoslovakia lung cancer screening study, combining over 17,000 smokers) had shown that early detection of lung cancer was possible with such programs, but mortality was not improved. Simply detecting a tumor at an earlier stage may not necessarily lead to improved survival. For example, plain chest X-ray screening resulted in increased time from diagnosis of cancer until death and those cancers being detected by screening tended to be earlier stages. However, these patients continued to die at the same rate as those who are not screened. At present, no professional or specialty organization advocates screening for lung cancer outside of clinical trial
s.
(CT) scan can uncover tumors not yet visible on an X-ray. This led to CT scanning being actively evaluated as a screening tool for lung cancer in high-risk patients.
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
. 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, 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.
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. 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.
The National Cancer Institute
funded a $300m study, the National Lung Screening Trial (NLST), which began in 2002, to compare the effectiveness of CT scan screening versus X-ray screening. This study, too, raised concern in the media over potential conflicts of interest related to the tobacco company, although this time on the contra-CT scan side: on October 8, 2007, the Wall Street Journal reported that at least two lead investigators of the study had conflicts of interest arising from their serving as paid, expert defense witnesses for the tobacco industry – one of them had given testimony asserting that promoting CT screening was "reckless or irresponsible", and another had provided an expert report warning that CT screening "may do more harm than good."
The National Cancer Institute' National Lung Screening Trial involved over 53,000 former and current heavy smokers aged 55 to 74, who either received three CT scans or three X-rays annually. Deaths in either group were then logged for up to five years. As of October 2010, 354 people in the CT scan group had died from lung cancer, versus 442 people in the X-ray group; in other words, deaths in the CT scan group of patients were 20.3% lower than in the X-ray group. The study's review board concluded that this difference was statistically significant
and recommended terminating the study. The director of the National Cancer Institute's director, Harold Varmus, said that early analysis results appeared to indicate that CT scans detected more lung cancers, at an earlier and more treatable stage, and that CT scans could therefore somewhat reduce the number of deaths in patients at high risk of lung cancer. Researchers associated with the study cautioned that the preliminary results did not constitute sufficient grounds to make the general public undergo CT scans and that further research and analysis of the data was necessary. The benefits of screening would have to be balanced against the risks associated with false positives – suspicious CT scan findings that in the end prove not to be cancer-related (although if the randomized data holds this demonstrates the benefits of screening outweigh the negatives of false positives on mortality) – and there is as yet no data showing how CT scan screening would benefit other sections of the population, such as people who had only smoked for shorter periods of time.
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
s before they cause symptoms, at a point where they are more likely to be curable. Screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
refers to the use of medical tests to detect disease in asymptomatic people. Screening studies have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because radiation exposure from repeated screening studies could actually induce cancer formation
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
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.
Practice guidelines
Clinical practice guidelines issued by the American College of Chest PhysiciansAmerican College of Chest Physicians
The American College of Chest Physicians is a medical organization in the United States consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, thoracic surgery, and critical care medicine....
in 2007 recommended against routine screening for lung cancer because of a lack of evidence that such screening was effective.
In 2004, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) gave a grade I recommendation indicating that "the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer".
Studies of efficacy
Regular chest radiography and sputumSputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
examination programs were not effective in reducing mortality from lung cancer. Previous studies (Mayo Lung Project and Czechoslovakia lung cancer screening study, combining over 17,000 smokers) had shown that early detection of lung cancer was possible with such programs, but mortality was not improved. Simply detecting a tumor at an earlier stage may not necessarily lead to improved survival. For example, plain chest X-ray screening resulted in increased time from diagnosis of cancer until death and those cancers being detected by screening tended to be earlier stages. However, these patients continued to die at the same rate as those who are not screened. At present, no professional or specialty organization advocates screening for lung cancer outside of clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s.
CT scans
A computed tomographyComputed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) scan can uncover tumors not yet visible on an X-ray. This led to CT scanning being actively evaluated as a screening tool for lung cancer in high-risk patients.
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
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
. 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, 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.
In contrast, a March 2007 study in the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
(JAMA) 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
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
had been funded indirectly by the parent company of the Liggett Group
Liggett Group
Liggett Group , formerly known as Liggett & Myers Tobacco Company, is the fourth largest tobacco company in the United States. Its headquarters are located in Durham, North Carolina, though its manufacturing facility is 30 miles to the west in Mebane, North Carolina...
, a tobacco company.
The National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
funded a $300m study, the National Lung Screening Trial (NLST), which began in 2002, to compare the effectiveness of CT scan screening versus X-ray screening. This study, too, raised concern in the media over potential conflicts of interest related to the tobacco company, although this time on the contra-CT scan side: on October 8, 2007, the Wall Street Journal reported that at least two lead investigators of the study had conflicts of interest arising from their serving as paid, expert defense witnesses for the tobacco industry – one of them had given testimony asserting that promoting CT screening was "reckless or irresponsible", and another had provided an expert report warning that CT screening "may do more harm than good."
The National Cancer Institute' National Lung Screening Trial involved over 53,000 former and current heavy smokers aged 55 to 74, who either received three CT scans or three X-rays annually. Deaths in either group were then logged for up to five years. As of October 2010, 354 people in the CT scan group had died from lung cancer, versus 442 people in the X-ray group; in other words, deaths in the CT scan group of patients were 20.3% lower than in the X-ray group. The study's review board concluded that this difference was statistically significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
and recommended terminating the study. The director of the National Cancer Institute's director, Harold Varmus, said that early analysis results appeared to indicate that CT scans detected more lung cancers, at an earlier and more treatable stage, and that CT scans could therefore somewhat reduce the number of deaths in patients at high risk of lung cancer. Researchers associated with the study cautioned that the preliminary results did not constitute sufficient grounds to make the general public undergo CT scans and that further research and analysis of the data was necessary. The benefits of screening would have to be balanced against the risks associated with false positives – suspicious CT scan findings that in the end prove not to be cancer-related (although if the randomized data holds this demonstrates the benefits of screening outweigh the negatives of false positives on mortality) – and there is as yet no data showing how CT scan screening would benefit other sections of the population, such as people who had only smoked for shorter periods of time.