Virginia A. Moyer, MD, MPH; on behalf of the U.S. Preventive Services Task Force *
Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government.
They should not be construed as an official position of the Agency for Healthcare Research and Quality
or the U.S. Department of Health and Human Services.
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mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.
Potential Conflicts of Interest: Disclosure forms from USPSTF members can be viewed at
Requests for Single Reprints: Reprints are available from the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lung
The USPSTF reviewed the evidence on the efficacy of low-dose computed tomography, chest radiography,
and sputum cytologic evaluation for lung cancer screening in asymptomatic persons who are at average
or high risk for lung cancer (current or former smokers) and the benefits and harms of these screening
tests and of surgical resection of early-stage non–small cell lung cancer. The USPSTF also
commissioned modeling studies to provide information about the optimum age at which to begin and end
screening, the optimum screening interval, and the relative benefits and harms of different screening
This recommendation applies to asymptomatic 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.
The USPSTF 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. (B recommendation)
Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force
Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice
Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit
Table. Screening Scenarios From CISNET Models
Tanu Pramanik, Lecturer (1); Hj Abdul Halim Hj Mansar, Professor (1) ; Narazah Mohd. Yusoff, Professor (2); Jogenananda Pramanik, Professor (1)
(1) Allianze University College of Medical Sciences, Kepala Batas-13200, Pulau Pinang, Malaysia and, (2) Advanced Dental and Medical Institute, University Sains Malaysia, Kepala Batas-13200, Pulau P
January 14, 2014
Simple, cost effective, minimally invasive or non-invasive molecular screening test for lung cancer A need of the hour!
Lung cancer-related mortality is one of the most common causes of cancer death worldwide. Detecting lung cancer at an earlier stage and, ideally, predicting who will develop the disease and particularly the most aggressive forms of cancer are presenting a daunting challenge. We studied with interest and sincerely applauded the insightful reviews on the efficacy of low-dose computed tomography, chest radiography, and sputum cytologic evaluation for lung cancer screening in asymptomatic persons who are at average or high risk for lung cancer (current or former smokers) and the benefits and harms of these screening tests and of surgical resection of early-stage non–small cell lung cancer (1, 2, 3).
Despite batteries of advanced screening techniques available in this 21st century, lung cancer alone continues to be the third most common cancerous condition causing cancer-related deaths in the United States (1), and 75% of lung cancer patients report with symptoms of advanced local or metastatic disease that result in poor prognosis (2). While appreciating the recent initiative for an update of the U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lung cancer, we accepted the crude reality that 95% of all low-dose-computerised tomography (LDCD) positive results do not necessarily lead to a diagnosis of cancer (1), and the harms associated with LDCD screening include false-negative and false-positive results, incidental findings, over-diagnosis, and risk of radiation exposure while false-positive LDCT results occur in a substantial proportion (4,5,6).
Since past two decades a considerable effort has been devoted to develop a cost effective non-invasive molecular screening test with higher predictive value to use for screening larger population at risk of lung cancer.
In recent years, a great potential has been documented in miRNA molecular profiling as a powerful diagnostic and prognostic biomarker in defining the signature of lung cancinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology (7).
MicroRNAs (miRNAs) are short, noncoding RNA molecules with regulatory function on protein-coding genes, and because of their fundamental role in development and differentiation, their involvement in the biological mechanisms underlying tumorigenesis, as well as their low complexity, stability, and easy detection, they represent a promising class of tissue- and blood-based biomarkers of cancer(8).
Two approaches are used to characterize miRNAs: studying expression of known miRNAs by hybridization-based techniques (e.g., northern blots, RNase protection, primer extension, real-time, quantitative PCR and microarrays) or discovery of novel miRNAs molecules by cloning and sequencing (9). various cancers were shown to leave specific miRNA fingerprints in the blood of patients suggesting that cell-free miRNAs could serve as non-invasive biomarkers for the detection or monitoring of cancer and putative therapeutic targets (10). Moreover, in a recent study, molecular researchers demonstrated that the profiling of 10-serum miRNAs provides a novel non-invasive biomarker for non-small cell lung Cancer (NSCLC) diagnosis (11).
“The 5-fold reduction in false positives obtained by combining the MicroRNA signature classifier (MSC) Lung Cancer assay to the results of the LDCT scan is of great clinical relevance in the context of reducing the false positive rate and the potential side effects associated with repeated LDCT scans or other unnecessary invasive diagnostic follow-ups,” stated Dr. Ugo Pastorino, Head of Thoracic Surgery Unit, Chairman of Department of Surgery, Istituto Nazionale dei Tumori, Milan, Italy (12).
1. Virginia A. Moyer, MD, MPH. Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Published online 31 December 2013 doi:10.7326/M13-2771
2. Humphrey L, Deffebach M, Pappas M, Baumann C, Artis K, Mitchell JP, et al. Screening for Lung Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation Statement. Evidence synthesis no. 105. AHRQ publication no. 13-05196-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
3. Humphrey LL, Deffebach M, Pappas M, Baumann C, Artis K, Mitchell JP, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2013;159:411-20. [PMID: 23897166]
4. Veronesi G, Maisonneuve P, Bellomi M, et al. Estimating over-diagnosis in low-dose computed tomography screening for lung cancer: a cohort study. Ann Intern Med. 2012;157:776-84. [PMID: 23208167]
5. de Koning HJ, Plevritis S, Hazelton WD, ten Haaf K, Munshi V, Jeon J, et al. Benefits and Harms of Computed Tomography Lung Cancer Screening Programs for High-Risk Populations. AHRQ publication no. 13-05196-EF-2. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
6. Bach PB, Mirkin JN, Oliver TK, Azzoli CG, Berry DA, Brawley OW, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA. 2012;307:2418-29. [PMID: 22610500]
7. Yanaihara N, Caplen N, Bowman E, et al., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006 Mar;9(3):189-98.
8. Ahmed FE. Role of miRNA in carcinogenesis and biomarker selection: a methodological view. Expert Rev Mol Diagn. 2007 Sep;7(5):569-603.
9. Boeri M, Pastorino U, Sozzi G., Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J. 2012 May-Jun;18(3):268-74. doi: 10.1097/PPO.0b013e318258b743.
10. Chen X, Hu Z, Wang W, Ba Y, Ma L, et al., Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel non-invasive biomarkers for non-small cell lung cancer diagnosis. Int J Cancer. 2012 Apr 1;130(7):1620-8. doi: 10.1002/ijc.26177. Epub 2011 Aug 3.
11. Zandberga E, Kozirovskis V, Ābols A, et al., Cell-free microRNAs as diagnostic, prognostic, and predictive biomarkers for lung cancer. Genes Chromosomes Cancer. 2013 Apr;52(4):356-69. doi: 10.1002/gcc.22032. Epub 2012 Dec 10.
12. Ugo Pastorino ( Gensignia Ltd., London,UK), Simple blood test can detect lung cancer with high sensitivity and specificity. Journal of Clinical Oncology, January 13, 2014. (http://www.redorbit.com/news/health/1113045405/simple-blood-test-can-detect-lung-cancer-with-high-sensitivity/).
Steven B. Zeliadt, PhD MPH, David H Au, MD MS
VA Seattle, Washington
January 23, 2014
Discussing Gender Differences in the Efficacy of Lung Cancer Screening
The US Preventive Services Task Force provided a “B” level recommendation for annual low-dose computed tomography screening among at-risk individuals between ages 55-80. While the USPSTF recommended that clinicians should individualize decision making based on a patient’s lung cancer risk – primarily driven by cumulative exposure to tobacco smoke – USPSTF’s evidence review omitted critical recent data about gender differences in the efficacy of LDCT screening.1,2 The recent publication of updated outcomes of the National Lung Screening Trial (NLST) at 8 years by Pinksy et al.3 highlights significant differences between women and men. This report found 158 (1.44%) lung cancer deaths among women randomized to LDCT screening compared to 215 (1.96%) deaths in the comparison group, and 311 (1.97%) lung cancer deaths among men randomized to LDCT compared to 337 (2.14%) in the comparison group.While these differences do not necessarily mean that men are at higher risk of developing or dying from lung, they do suggest that men may not benefit as much as women from lung cancer screening. Based on these data, for women, the number needed to screen (NNS) to avoid one lung cancer death is 194, while for men this number jumps to 603. Put another way, for every 1000 eligible patients who undergo screening, 5.2 (95% CI 1.9 to 7.8) women are likely to benefit compared to 1.7 (95% CI -1.7 to 4.3) men. When these benefits are compared alongside the potential harms of screening, it is possible women and men may make different choices. For example, of the 1000 hypothetical individuals considering screening, nearly 250 will have some type of suspicious finding requiring repeat testing or invasive procedure, and around 11 will have a complication such as a pneumothorax. Given that NLST was conducted by large academic centers with expertise in radiology and cancer care, it is possible that these harms may be higher in the community.These differences by gender should not be surprising. Solitary pulmonary nodules are most often adenocarcinomas that also present more commonly in women.4,5 Although the reason is unknown, the implications are critical to the implementation and effectiveness of lung cancer screening in men. As we begin to individualize the discussions of screening with patients, these results suggest that we need to have different conversations about the risks and benefits of screening for women and men.Steven B. Zeliadt, PhD MPHInvestigator, Center of Innovation for Veteran-Centered and Value Driven Care, Seattle, WA.Steven.Zeliadt@VA.govDavid H Au, MD MSActing Director, Center of Innovation for Veteran-Centered and Value Driven Care, Seattle, WA.David.Au@VA.gov1. Moyer VA on behalf of USPSTF. Screening for lung cancer: U.S. Preventive Services Ann Intern Med. Dec 31; 2013 2. Humphrey LL, Deffebach M, Pappas M, Baumann C, Artis K, Mitchell JP, Zakher B, Fu R, Slatore CG. Screening for lung cancer with low-dose computed tomography: A systematic review to update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med. Sep 17;159(6):411-20; 20133. Pinsky PF, Church TR, Izmirlian G, Kramer BS. The National Lung Screening Trial: Results Stratified by Demographics, Smoking History, and Lung Cancer Histology. Cancer. Aug 23; 20134. Fu JB, Kau TY, Severson RK, Kalemkerian GP. Lung cancer in women: Analysis of the National Surveillance Epidemiology, and End Results Database. Chest. 127(3): 768-777; 2005. 5. Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, Ost DE; American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest Sep 132(3 Suppl): 108S-130S.
Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation
Statement. Ann Intern Med. 2014;160:330–338. doi: https://doi.org/10.7326/M13-2771
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Published: Ann Intern Med. 2014;160(5):330-338.
Cancer Screening/Prevention, Guidelines, Hematology/Oncology, Lung Cancer, Prevention/Screening.
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