Clinical Review & Education
JAMA Clinical Guidelines Synopsis
Lung Cancer Screening Andrew M. Davis, MD, MPH; Adam S. Cifu, MD
GUIDELINE TITLE Screening for Lung Cancer DEVELOPER US Preventive Services Task Force (USPSTF) RELEASE DATE 12/31/2013 (online); 3/4/2014 (print) PRIOR VERSION 5/4/2004 FUNDING SOURCE US federal government (Agency for
Healthcare Research and Quality) TARGET POPULATION Asymptomatic adults aged 55 to 80 years
who have a 30 pack-year smoking history and currently smoke or have quit smoking within the past 15 years MAJOR RECOMMENDATION AND RATING Screen annually for lung
cancer with low-dose computed tomography in adults. Discontinue screening when the patient has not smoked for 15
Summary of the Clinical Problem Lung cancer is the leading cause of cancer-related mortality in the UnitedStates,with159 000deathsestimatedin2014.Ageolderthan 55 years and smoking are the strongest risk factors for lung cancer. Smokingcessationisthemainintervention to prevent lung canViewpoint page 1193 and cerinthe20%ofAmericanswho Editorials pages 1206 and 1208 continue to smoke, but only 15% of cessation efforts succeed. Outcomes in lung cancer depend crucially on the stage of diagnosis, with 5-year survival for non–small cell lung cancer estimated at 71% to 90% for stage IA and 42% to 75% for stage IB cases, compared with less than 10% for those diagnosed with stage IV.1 Currently only 15% of lung cancer cases are diagnosed at stage I, and large trials have not supported the value of chest radiography or sputum cytology for screening.2 Low-dose computed tomography (CT) has emerged as a potentially useful screening method, with 55% to 85% of detected cancers found to be stage I.3,4 Approximately 9 million Americans would potentially be eligible for this screening guideline, divided roughly equally between current smokers and former smokers who have quit within the past 15 years.
Characteristics of the Guideline Source TheguidelinewasdevelopedbytheUSPreventiveServicesTaskForce, which is an independent volunteer panel of nonfederal experts in prevention and evidence-based medicine. The task force is composed of primary care clinicians and experts in methodology and health behavior. The guidelines were developed in coordination with a systematic review sponsored by the Agency for Healthcare Research and Quality (AHRQ). A conflict of interest disclosure is completed by task force members prior to each meeting to provide information to AHRQ 1248
years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) Related guidelines and other resources American College of Chest Physicians. Evaluation of Individuals With Pulmonary Nodules: When Is It Lung Cancer? Diagnosis and Management of Lung Cancer: Evidence-Based Clinical Practice Guidelines. 2013. http://journal.publications .chestnet.org/data/Journals/CHEST/926876/chest_143_5 _suppl_e93S.pdf The American Association for Thoracic Surgery Guidelines for Lung Cancer Screening Using Low-Dose Computed Tomography Scans for Lung Cancer Survivors and Other High-Risk Groups. 2012. http://aats.org /multimedia/files/Guidelines/Lung-Cancer-Screening-Using-low-dose -computed-tomography-scans.pdf US Preventive Services Task Force. Counseling and Interventions to Prevent Tobacco Use and Tobacco-Caused Disease in Adults and Pregnant Women. 2009. http://annals.org/data/Journals/AIM/20180 /0000605-200904210-00009.pdf
on potential financial, business/professional, and intellectual conflicts of interest related to the topics addressed (Table).
Evidence Base Eight randomized clinical trials have been reported on the effectiveness of low-dose CT in lung cancer screening, with 3 thought to be of sufficient quality and follow-up to be included in a recent meta-analysis.2 The largest trial was the National Lung Screening Trial (NLST), which included more than 50 000 asymptomatic US adults, aged 55 to 74 years, with at least a 30 pack-year smoking history. The NLST studied the value of 3 annual low-dose CT screenings compared with 3 annual single-view chest x-rays. After 6 to 7 years of follow-up, there was a reduction in lung cancer mortality of 16%. Allcause mortality was reduced by 6.7%. A reduction in all-cause mortality was not seen in other trials. Extensive microsimulation modeling performed as part of the meta-analysis explored several key Table. Guideline Rating Standard
Rating
1. Establishing transparency
Good
2. Management of conflict of interest in the guideline development group
Good
3. Guideline development group composition
Good
4. Clinical practice guideline–systematic review intersection
Good
5. Establishing evidence foundations and rating strength for each of the guideline recommendations
Good
6. Articulation of recommendations
Good
7. External review
Good
8. Updating
Fair
9. Implementation issues
Fair
JAMA September 24, 2014 Volume 312, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Carleton University User on 05/11/2015
jama.com
JAMA Clinical Guidelines Synopsis Clinical Review & Education
variables based on a US cohort born in 1950 and determined that the best balance of benefits and harms was achieved for adults aged 55 to 80 years, with a 30 pack-year smoking history, and current smoking or cessation within 15 years.1
Benefits and Harms A systematic review was conducted as part of the guideline development.2 Combining the 3 trials judged to be of fair or good quality in this meta-analysis, there was a reduction in lung cancer mortality with low-dose CT screening (relative risk, 0.81; 95% CI, 0.72-0.91).1 The principal harms associated with low-dose CT screening are falsenegative and false-positive results, overdiagnosis, radiation exposure, incidental findings, psychological distress, financial strain, and the opportunity cost of diversion from other health-related, work, and personal activities.5,6 In the NLST nearly 24.2% of screening results were positive and 96.4% of these results were false-positives, with the positive predictive value of the finding of a pulmonary nodule (ⱖ4 mm) only 3.8%. About 2.5% of positive results (17 053) in NLST required invasive diagnostic procedures such as bronchoscopy, needle biopsy, or thoracoscopy. In the setting of the high-quality diagnostic and interventional expertise present in centers conducting the NLST, there were 61 complications and 6 deaths following a diagnostic procedure.1 Some degree of overdiagnosis probably exists, based on studies and modeling that suggest that 10% to 25% of cancer cases detected by low-dose CT are slow-growing or indolent.5 Radiation exposure for a single scan is about 1 mSv (annual background radiation exposure in the United States is approximately 2.4 mSv). Even with improved lower-dose technology, multiple annual screens and follow-up diagnostic chest CT (~8 mSv) or positron emission tomography (PET) (~14 mSv), the latter performed in 5.5% of screened NLST participants, can substantially increase exposures. Literature is limited regarding the potential for harm due to anxiety and for the costs associated with screening and follow-up testing.6 Smoking rates are not consistently affected by participation in low-dose CT screening, although abnormal screening results may encourage cessation.5
Discussion Controversy among various medical societies and as assessed by the Medicare Evidence Development and Coverage Advisory Committee over acceptance of this guideline focuses on 3 issues: the precise
eligibility criteria for screening, whether low-dose CT screening can be implemented safely and effectively in the community, and lack of consensus on the likely balance of benefits and harms. A 2012 systematic review on behalf of the American College of Chest Physicians, the American Society of Clinical Oncology, and the American Thoracic Society endorsed low-dose CT screening for lung cancer based on the NLST criteria (age 55-74 years, 30 pack-year smoking history, current smokers or having quit in the past 15 years), and the American Cancer Society used the same criteria in its 2013 guideline. The American Association for Thoracic Surgery extends the upper age of routine screening to 79 years. The 2013 revision of the National Comprehensive Cancer Network guideline further recommends screening for persons 50 to 54 years who have at least a 20 packyear smoking history and one additional risk factor, and beyond age 74 years if candidates are “still candidates for definitive therapy.” In contrast, the American Academy of Family Medicine currently terms the evidence for routine screening “insufficient to recommend for or against,” suggesting that “a shared decisionmaking discussion between the clinician and patient should occur regarding the benefits and potential harms of screening for lung cancer.” In April 2014, the Medicare Evidence Development Coverage Advisory Committee expressed a vote of low confidence on whether the benefits of low-dose CT screening would outweigh its harms among Medicare beneficiaries in a community setting.7
Areas in Need of Future Study or Ongoing Research Attempts to reduce the number of false-positive low-dose CT results and unnecessary procedures include modeling to identify higher-risk cohorts within the NLST criteria, greater size thresholds for repeat screening, and greater use of preoperative PET scans.5 The management of screen-detected ground glass opacities remains challenging. Given controversies regarding the balance of benefit and harms, commentators have called for carefully defining the basis under which to cover low-dose CT screening, offering such coverage only in the context of facilities that have been certified as having comprehensive, patient-centered programs designed to maximize benefits and minimize harms. Such a program would include rigorous procedures to ensure that only high-risk persons meeting eligibility criteria are screened andwouldprovideshareddecisionmaking,integrationofsmokingcessation services, and a comprehensive multidisciplinary process for protocol-based evaluation of screen-detected abnormalities.7,8
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Section of General Internal Medicine, University of Chicago, Chicago, Illinois (Davis); Department of Medicine, University of Chicago (Cifu).
1. Moyer VA; US Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(5):330-338.
Corresponding Author: Andrew M. Davis, MD, MPH, Section of General Internal Medicine, University of Chicago, 5841 S Maryland Ave, MC3051, Chicago, IL 60637 ([email protected]).
2. Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2013;159(6):411-420.
Section Editor: Edward H. Livingston, MD, Deputy Editor, JAMA. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
3. Boiselle PM. Computed tomography screening for lung cancer. JAMA. 2013;309(11):1163-1170. 4. Aberle DR, Adams AM, Berg CD, et al; National Lung Screening Trial research team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5): 395-409.
jama.com
5. Tammemagi MC, Lam S. Screening for lung cancer using low dose computed tomography. BMJ. 2014;348:g2253. 6. Harris RP, Sheridan SL, Lewis CL, et al. The harms of screening: a proposed taxonomy and application to lung cancer screening. JAMA Intern Med. 2014;174(2):281-285. 7. Wiener RS. Balancing the benefits and harms of low-dose computed tomography screening for lung cancer: Medicare's options for coverage [published online June 24, 2014]. Ann Intern Med. 2014. 8. Menezes R, Roberts H. Lung cancer screening using low-dose computed tomography: keeping participants out of harm’s way. J Thorac Oncol. 2014;9(7):912-913.
JAMA September 24, 2014 Volume 312, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Carleton University User on 05/11/2015
1249
JAMA Clinical Guidelines Synopsis
Lung Cancer Screening Andrew M. Davis, MD, MPH; Adam S. Cifu, MD
GUIDELINE TITLE Screening for Lung Cancer DEVELOPER US Preventive Services Task Force (USPSTF) RELEASE DATE 12/31/2013 (online); 3/4/2014 (print) PRIOR VERSION 5/4/2004 FUNDING SOURCE US federal government (Agency for
Healthcare Research and Quality) TARGET POPULATION Asymptomatic adults aged 55 to 80 years
who have a 30 pack-year smoking history and currently smoke or have quit smoking within the past 15 years MAJOR RECOMMENDATION AND RATING Screen annually for lung
cancer with low-dose computed tomography in adults. Discontinue screening when the patient has not smoked for 15
Summary of the Clinical Problem Lung cancer is the leading cause of cancer-related mortality in the UnitedStates,with159 000deathsestimatedin2014.Ageolderthan 55 years and smoking are the strongest risk factors for lung cancer. Smokingcessationisthemainintervention to prevent lung canViewpoint page 1193 and cerinthe20%ofAmericanswho Editorials pages 1206 and 1208 continue to smoke, but only 15% of cessation efforts succeed. Outcomes in lung cancer depend crucially on the stage of diagnosis, with 5-year survival for non–small cell lung cancer estimated at 71% to 90% for stage IA and 42% to 75% for stage IB cases, compared with less than 10% for those diagnosed with stage IV.1 Currently only 15% of lung cancer cases are diagnosed at stage I, and large trials have not supported the value of chest radiography or sputum cytology for screening.2 Low-dose computed tomography (CT) has emerged as a potentially useful screening method, with 55% to 85% of detected cancers found to be stage I.3,4 Approximately 9 million Americans would potentially be eligible for this screening guideline, divided roughly equally between current smokers and former smokers who have quit within the past 15 years.
Characteristics of the Guideline Source TheguidelinewasdevelopedbytheUSPreventiveServicesTaskForce, which is an independent volunteer panel of nonfederal experts in prevention and evidence-based medicine. The task force is composed of primary care clinicians and experts in methodology and health behavior. The guidelines were developed in coordination with a systematic review sponsored by the Agency for Healthcare Research and Quality (AHRQ). A conflict of interest disclosure is completed by task force members prior to each meeting to provide information to AHRQ 1248
years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) Related guidelines and other resources American College of Chest Physicians. Evaluation of Individuals With Pulmonary Nodules: When Is It Lung Cancer? Diagnosis and Management of Lung Cancer: Evidence-Based Clinical Practice Guidelines. 2013. http://journal.publications .chestnet.org/data/Journals/CHEST/926876/chest_143_5 _suppl_e93S.pdf The American Association for Thoracic Surgery Guidelines for Lung Cancer Screening Using Low-Dose Computed Tomography Scans for Lung Cancer Survivors and Other High-Risk Groups. 2012. http://aats.org /multimedia/files/Guidelines/Lung-Cancer-Screening-Using-low-dose -computed-tomography-scans.pdf US Preventive Services Task Force. Counseling and Interventions to Prevent Tobacco Use and Tobacco-Caused Disease in Adults and Pregnant Women. 2009. http://annals.org/data/Journals/AIM/20180 /0000605-200904210-00009.pdf
on potential financial, business/professional, and intellectual conflicts of interest related to the topics addressed (Table).
Evidence Base Eight randomized clinical trials have been reported on the effectiveness of low-dose CT in lung cancer screening, with 3 thought to be of sufficient quality and follow-up to be included in a recent meta-analysis.2 The largest trial was the National Lung Screening Trial (NLST), which included more than 50 000 asymptomatic US adults, aged 55 to 74 years, with at least a 30 pack-year smoking history. The NLST studied the value of 3 annual low-dose CT screenings compared with 3 annual single-view chest x-rays. After 6 to 7 years of follow-up, there was a reduction in lung cancer mortality of 16%. Allcause mortality was reduced by 6.7%. A reduction in all-cause mortality was not seen in other trials. Extensive microsimulation modeling performed as part of the meta-analysis explored several key Table. Guideline Rating Standard
Rating
1. Establishing transparency
Good
2. Management of conflict of interest in the guideline development group
Good
3. Guideline development group composition
Good
4. Clinical practice guideline–systematic review intersection
Good
5. Establishing evidence foundations and rating strength for each of the guideline recommendations
Good
6. Articulation of recommendations
Good
7. External review
Good
8. Updating
Fair
9. Implementation issues
Fair
JAMA September 24, 2014 Volume 312, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Carleton University User on 05/11/2015
jama.com
JAMA Clinical Guidelines Synopsis Clinical Review & Education
variables based on a US cohort born in 1950 and determined that the best balance of benefits and harms was achieved for adults aged 55 to 80 years, with a 30 pack-year smoking history, and current smoking or cessation within 15 years.1
Benefits and Harms A systematic review was conducted as part of the guideline development.2 Combining the 3 trials judged to be of fair or good quality in this meta-analysis, there was a reduction in lung cancer mortality with low-dose CT screening (relative risk, 0.81; 95% CI, 0.72-0.91).1 The principal harms associated with low-dose CT screening are falsenegative and false-positive results, overdiagnosis, radiation exposure, incidental findings, psychological distress, financial strain, and the opportunity cost of diversion from other health-related, work, and personal activities.5,6 In the NLST nearly 24.2% of screening results were positive and 96.4% of these results were false-positives, with the positive predictive value of the finding of a pulmonary nodule (ⱖ4 mm) only 3.8%. About 2.5% of positive results (17 053) in NLST required invasive diagnostic procedures such as bronchoscopy, needle biopsy, or thoracoscopy. In the setting of the high-quality diagnostic and interventional expertise present in centers conducting the NLST, there were 61 complications and 6 deaths following a diagnostic procedure.1 Some degree of overdiagnosis probably exists, based on studies and modeling that suggest that 10% to 25% of cancer cases detected by low-dose CT are slow-growing or indolent.5 Radiation exposure for a single scan is about 1 mSv (annual background radiation exposure in the United States is approximately 2.4 mSv). Even with improved lower-dose technology, multiple annual screens and follow-up diagnostic chest CT (~8 mSv) or positron emission tomography (PET) (~14 mSv), the latter performed in 5.5% of screened NLST participants, can substantially increase exposures. Literature is limited regarding the potential for harm due to anxiety and for the costs associated with screening and follow-up testing.6 Smoking rates are not consistently affected by participation in low-dose CT screening, although abnormal screening results may encourage cessation.5
Discussion Controversy among various medical societies and as assessed by the Medicare Evidence Development and Coverage Advisory Committee over acceptance of this guideline focuses on 3 issues: the precise
eligibility criteria for screening, whether low-dose CT screening can be implemented safely and effectively in the community, and lack of consensus on the likely balance of benefits and harms. A 2012 systematic review on behalf of the American College of Chest Physicians, the American Society of Clinical Oncology, and the American Thoracic Society endorsed low-dose CT screening for lung cancer based on the NLST criteria (age 55-74 years, 30 pack-year smoking history, current smokers or having quit in the past 15 years), and the American Cancer Society used the same criteria in its 2013 guideline. The American Association for Thoracic Surgery extends the upper age of routine screening to 79 years. The 2013 revision of the National Comprehensive Cancer Network guideline further recommends screening for persons 50 to 54 years who have at least a 20 packyear smoking history and one additional risk factor, and beyond age 74 years if candidates are “still candidates for definitive therapy.” In contrast, the American Academy of Family Medicine currently terms the evidence for routine screening “insufficient to recommend for or against,” suggesting that “a shared decisionmaking discussion between the clinician and patient should occur regarding the benefits and potential harms of screening for lung cancer.” In April 2014, the Medicare Evidence Development Coverage Advisory Committee expressed a vote of low confidence on whether the benefits of low-dose CT screening would outweigh its harms among Medicare beneficiaries in a community setting.7
Areas in Need of Future Study or Ongoing Research Attempts to reduce the number of false-positive low-dose CT results and unnecessary procedures include modeling to identify higher-risk cohorts within the NLST criteria, greater size thresholds for repeat screening, and greater use of preoperative PET scans.5 The management of screen-detected ground glass opacities remains challenging. Given controversies regarding the balance of benefit and harms, commentators have called for carefully defining the basis under which to cover low-dose CT screening, offering such coverage only in the context of facilities that have been certified as having comprehensive, patient-centered programs designed to maximize benefits and minimize harms. Such a program would include rigorous procedures to ensure that only high-risk persons meeting eligibility criteria are screened andwouldprovideshareddecisionmaking,integrationofsmokingcessation services, and a comprehensive multidisciplinary process for protocol-based evaluation of screen-detected abnormalities.7,8
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Section of General Internal Medicine, University of Chicago, Chicago, Illinois (Davis); Department of Medicine, University of Chicago (Cifu).
1. Moyer VA; US Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(5):330-338.
Corresponding Author: Andrew M. Davis, MD, MPH, Section of General Internal Medicine, University of Chicago, 5841 S Maryland Ave, MC3051, Chicago, IL 60637 ([email protected]).
2. Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2013;159(6):411-420.
Section Editor: Edward H. Livingston, MD, Deputy Editor, JAMA. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
3. Boiselle PM. Computed tomography screening for lung cancer. JAMA. 2013;309(11):1163-1170. 4. Aberle DR, Adams AM, Berg CD, et al; National Lung Screening Trial research team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5): 395-409.
jama.com
5. Tammemagi MC, Lam S. Screening for lung cancer using low dose computed tomography. BMJ. 2014;348:g2253. 6. Harris RP, Sheridan SL, Lewis CL, et al. The harms of screening: a proposed taxonomy and application to lung cancer screening. JAMA Intern Med. 2014;174(2):281-285. 7. Wiener RS. Balancing the benefits and harms of low-dose computed tomography screening for lung cancer: Medicare's options for coverage [published online June 24, 2014]. Ann Intern Med. 2014. 8. Menezes R, Roberts H. Lung cancer screening using low-dose computed tomography: keeping participants out of harm’s way. J Thorac Oncol. 2014;9(7):912-913.
JAMA September 24, 2014 Volume 312, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Carleton University User on 05/11/2015
1249
