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Original Research

The National Lung Screening Trial: Overview and Study Design

Published Online:Jan 1 2011https://doi.org/10.1148/radiol.10091808

Abstract

The National Lung Screening Trial is a multicenter, randomized controlled trial comparing low-dose helical CT with chest radiography in the screening of current and former heavy smokers for lung cancer.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

© RSNA, 2010

Clinical trial registration no. NCT 00047385

Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10091808/-/DC1

References

  • 1 Harris RP, Helfand M, Woolf SH, et al.. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20(3 suppl):21–35.
    MedlineGoogle Scholar
  • 2 Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin 2002;52(1):23–47.
    MedlineGoogle Scholar
  • 3 National Cancer Institute, US National Institutes of Health, Surveillance, Epidemiology and End Results. (SEER Program). CSR section 15: lung and bronchus cancer pdf. http://seer.cancer.gov/csr/1975_2002. Accessed January 7, 2009.
    Google Scholar
  • 4 Jemal A, Thun MJ, Ries LA, et al.. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 2008;100(23):1672–1694.
    MedlineGoogle Scholar
  • 5 Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults: United States, 2002. MMWR Morb Mortal Wkly Rep 2004;53(20):427–431.
    MedlineGoogle Scholar
  • 6 Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults: United States, 2007. MMWR Morb Mortal Wkly Rep 2008;57(45):1221–1226. [Published correction appears in MMWR Morb Mortal Wkly Rep 2008;57(47):1281.].
    MedlineGoogle Scholar
  • 7 Blot WJ, Fraumeni JF. Cancer of the lung and pleura. In: Schottenfeld DFraumeni JF, eds. Cancer epidemiology and prevention. New York, NY: Oxford University Press, 1996;637–665.
    Google Scholar
  • 8 Crispo A, Brennan P, Jöckel KH, et al.. The cumulative risk of lung cancer among current, ex- and never-smokers in European men. Br J Cancer 2004;91(7):1280–1286.
    MedlineGoogle Scholar
  • 9 Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111(6):1710–1717.
    MedlineGoogle Scholar
  • 10 Black WC, Welch HG. Screening for disease. AJR Am J Roentgenol 1997;168(1):3–11.
    MedlineGoogle Scholar
  • 11 Flehinger BJ, Melamed MR, Zaman MB, Heelan RT, Perchick WB, Martini N. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. Am Rev Respir Dis 1984;130(4):555–560.
    MedlineGoogle Scholar
  • 12 Melamed MR. Lung cancer screening results in the National Cancer Institute New York study. Cancer 2000;89(11 suppl):2356–2362.
    MedlineGoogle Scholar
  • 13 Frost JK, Ball WC, Levin ML, et al.. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 1984;130(4):549–554.
    MedlineGoogle Scholar
  • 14 Tockman MS. Survival and mortality from lung cancer in a screened population: The Johns Hopkins Study. Chest 1986;89(suppl):324S–325S.
    MedlineGoogle Scholar
  • 15 Fontana RS, Sanderson DR, Taylor WF, et al.. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 1984;130(4):561–565.
    MedlineGoogle Scholar
  • 16 Fontana RS, Sanderson DR, Woolner LB, et al.. Screening for lung cancer: a critique of the Mayo Lung Project. Cancer 1991;67(4 suppl):1155–1164.
    MedlineGoogle Scholar
  • 17 Marcus PM, Bergstralh EJ, Fagerstrom RM, et al.. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst 2000;92(16):1308–1316.
    MedlineGoogle Scholar
  • 18 Kubík A, Polák J. Lung cancer detection: results of a randomized prospective study in Czechoslovakia. Cancer 1986;57(12):2427–2437.
    MedlineGoogle Scholar
  • 19 Kubík AK, Parkin DM, Zatloukal P. Czech study on lung cancer screening: post-trial follow-up of lung cancer deaths up to year 15 since enrollment. Cancer 2000;89(11 suppl):2363–2368.
    MedlineGoogle Scholar
  • 20 Wynder EL, Muscat JE. The changing epidemiology of smoking and lung cancer histology. Environ Health Perspect 1995;103(suppl 8):143–148.
    MedlineGoogle Scholar
  • 21 Schrump DS, Giaccone G, Kelsey CR, Marks LB. Non small-cell lung cancer. In: DeVita VTLawrence TSRosenberg SA, eds. Cancer: principles and practice of oncology. Philadelphia, Pa: Lippincott, Williams & Wilkins, 2008;896–946.
    Google Scholar
  • 22 National Cancer Institute, US National Institutes of Health, Surveillance, Epidemiology and End Results. (SEER Program). CSR section 15: lung and bronchus cancer pdf. http://seer.cancer.gov/csr/1975_2005. Accessed January 27, 2009.
    Google Scholar
  • 23 Gohagan JK, Prorok PC, Hayes RB, Kramer BSProstate, Lung, Colorectal and Ovarian Cancer Screening Trial Project Team. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization, and status. Control Clin Trials 2000;21(6 suppl):251S–272S.
    MedlineGoogle Scholar
  • 24 Prorok PC, Andriole GL, Bresalier RS, et al.. Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trials 2000;21(6 suppl):273S–309S.
    MedlineGoogle Scholar
  • 25 Oken MM, Marcus PM, Hu P, et al.. Baseline chest radiograph for lung cancer detection in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. J Natl Cancer Inst 2005;97(24):1832–1839.
    MedlineGoogle Scholar
  • 26 Sone S, Li F, Yang ZG, et al.. Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner. Br J Cancer 2001;84(1):25–32.
    MedlineGoogle Scholar
  • 27 Nawa T, Nakagawa T, Kusano S, Kawasaki Y, Sugawara Y, Nakata H. Lung cancer screening using low-dose spiral CT: results of baseline and 1-year follow-up studies. Chest 2002;122(1):15–20.
    MedlineGoogle Scholar
  • 28 Sobue T, Moriyama N, Kaneko M, et al.. Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer association project. J Clin Oncol 2002;20(4):911–920.
    MedlineGoogle Scholar
  • 29 Henschke CI, McCauley DI, Yankelevitz DF, et al.. Early lung cancer action project: overall design and findings from baseline screening. Lancet 1999;354(9173):99–105.
    MedlineGoogle Scholar
  • 30 Henschke CI, Naidich DP, Yankelevitz DF, et al.. Early lung cancer action project: initial findings on repeat screenings. Cancer 2001;92(1):153–159.
    MedlineGoogle Scholar
  • 31 Swensen SJ, Jett JR, Sloan JA, et al.. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med 2002;165(4):508–513.
    MedlineGoogle Scholar
  • 32 Diederich S, Wormanns D, Semik M, et al.. Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic smokers. Radiology 2002;222(3):773–781.
    Google Scholar
  • 33 Gohagan J, Marcus P, Fagerstrom R, et al.. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the Lung Screening Study of the National Cancer Institute. Chest 2004;126(1):114–121.
    MedlineGoogle Scholar
  • 34 Gohagan JK, Marcus PM, Fagerstrom RM, et al.. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47(1):9–15.
    MedlineGoogle Scholar
  • 35 Church TRNational Lung Screening Trial Executive Committee. Chest radiography as the comparison for spiral CT in the National Lung Screening Trial. Acad Radiol 2003;10(6):713–715.
    MedlineGoogle Scholar
  • 36 American College of Radiology. ACR standard for performance of pediatric and adult thoracic computed tomography (CT). In: Standards 2003-2004. Reston, Va: American College of Radiology, 2002;115–119.
    Google Scholar
  • 37 Zhu X, Yu J, Huang Z. Low-dose chest CT: optimizing radiation protection for patients. AJR Am J Roentgenol 2004;183(3):809–816.
    MedlineGoogle Scholar
  • 38 ACRIN/NLST CT Technique Comparison Chart. American College of Radiology Imaging Network. http://www.acrin.org/Portals/0/Protocols/6654/forms/qcforms/CT_Technique_Chart.pdf. Accessed July 5, 2010.
    Google Scholar
  • 39 Cagnon CH, Cody DD, McNitt-Gray MF, Seibert JA, Judy PF, Aberle DR. Description and implementation of a quality control program in an imaging-based clinical trial. Acad Radiol 2006;13(11):1431–1441.
    MedlineGoogle Scholar
  • 40 International Commission on Radiological Protection. Managing patient dose in computed tomography. Publication 87. Oxford, England: Elsevier, 2001.
    Google Scholar
  • 41 American College of Radiology. ACR standard for performance of pediatric and adult chest radiography. In: Standards 2002-2003. Reston, Va: American College of Radiology, 2001;105–109.
    Google Scholar
  • 42 Taylor WF, Fontana RS. Biometric design of the Mayo Lung Project for early detection and localization of bronchogenic carcinoma. Cancer 1972;30(5):1344–1347.
    MedlineGoogle Scholar
  • 43 Hu P, Zelen M.. Planning clinical trials to evaluate early detection programmes. Biometrika 1997;84(4):817–829.
    Google Scholar
  • 44 Fontana R. Early detection of lung cancer: The Mayo Lung Project. In: Prorok PCMiller AB, eds. Screening for cancer. I. General principles on evaluation of screening for cancer and screening for lung, bladder and oral cancer. Geneva, Switzerland: International Union Against Cancer, 1984;107–122.
    Google Scholar
  • 45 Jennison C, Turnbull BW. Group sequential methods with applications to clinical trials. Boca Raton, Fla: Chapman & Hall/CRC, 2000.
    Google Scholar
  • 46 Gold MRSiegel JERussell LBWeinstein MC, eds. Cost-effectiveness in health and medicine. New York, NY: Oxford University Press, 1996.
    Google Scholar
  • 47 van Iersel CA, de Koning HJ, Draisma G, et al.. Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer 2007;120(4):868–874.
    MedlineGoogle Scholar
  • 48 van den Bergh KA, Essink-Bot ML, Bunge EM, et al.. Impact of computed tomography screening for lung cancer on participants in a randomized controlled trial (NELSON trial). Cancer 2008;113(2):396–404.
    MedlineGoogle Scholar
  • 49 Picozzi G, Paci E, Lopez Pegna A, et al.. Screening of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial “Italung-CT”. Radiol Med (Torino) 2005;109(1-2):17–26.
    MedlineGoogle Scholar
  • 50 Infante M, Lutman FR, Cavuto S, et al.. Lung cancer screening with spiral CT: baseline results of the randomized DANTE trial. Lung Cancer 2008;59(3):355–363.
    MedlineGoogle Scholar
  • 51 Burns DM. Primary prevention, smoking, and smoking cessation: implications for future trends in lung cancer prevention. Cancer 2000;89(11 suppl):2506–2509.
    MedlineGoogle Scholar

Article History

Received November 30, 2009; revision requested December 16; revision received June 21, 2010; accepted June 25; final version accepted July 20.
Published online: Jan 2011
Published in print: Jan 2011