Lung Cancer Screening

Lung cancer is the leading cause of cancer-related death in the United States, with 90% of cases being fatal. The vast majority of cases are associated with smoking, and thus smoking cessation is encouraged to reduce a patient’s lifetime risk. Annual screening with low-dose computed tomography is recommended for early detection in patients 50–80 years of age with a significant smoking history. This screening program has been shown to significantly reduce mortality.

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Overview

Lung cancer

Lung cancer is a malignant tumor of the lung originating from the respiratory epithelium of the bronchi, bronchioles, and alveoli.

Epidemiology

  • Lung cancer is the leading cause of cancer-related death in the United States.
    • 90% of cases are fatal.
    • 5-year survival in approximately 18% of cases (even with advances in treatment)
    • Annual deaths:
      • 160,000 in the United States
      • 1.6 million worldwide
  • 230,000 new cases are reported annually in the United States.
    • Accounts for 13% of all cancer cases
  • Incidence increases with age:
    • Rare under the age of 50 years
    • Incidence peaks at ages 75–79 years.
  • 85%‒90% of lung cancer cases are attributed to smoking.

Risk factors

  • Smoking (most common):
    • Increased risk related to the number of cigarettes smoked, in pack-years (py) (py = number of cigarettes smoked daily x number of years smoked) / 20.
    • Smoking at a lower intensity for a long time: more likely to develop lung cancer than smoking at a higher intensity for a shorter time
    • The association with electronic cigarettes is not yet clear.
  • Environmental exposures:
    • 2nd-hand smoke
    • Air pollution
    • Asbestos
    • Radon
    • Chromium
    • Nickel
    • Arsenic
    • Polycyclic aromatic hydrocarbons
  • Radiation treatment
  • Lung disease:
    • Idiopathic pulmonary fibrosis
    • Alpha-1 antitrypsin deficiency
    • Chronic obstructive pulmonary disease (COPD)
  • Human immunodeficiency virus (HIV) infection
  • Family history
  • Alcohol consumption

Risk factor reduction

Smoking cessation reduces the risk of lung cancer.

  • Most important factor
  • The greatest benefit is seen in those who quit by age 30.
  • 39% lower risk 5 years after quitting (after a median history of 21 py)
  • 41% of the lung cancers in former smokers occur 15 years after quitting.
  • Dietary changes may be of benefit (not well established).
  • Quitting smoking also lowers the risk for other diseases/conditions (such as other cancers, atherosclerosis, and chronic obstructive pulmonary disease).

Screening Rationale

Benefits of screening

  • Goal is to detect early disease, which is:
    • More amenable to treatment
    • Associated with better prognosis
  • Several studies also show a favorable association with smoking cessation.

Risks of screening

  • High false-positive rate
  • Most abnormalities detected are benign nodules.
  • Leads to unnecessary biopsy or surgery
  • Increased radiation exposure
  • Overdiagnosis: 
    • Detection of cancers that would not have affected morbidity or mortality for the patient
    • Leads to unnecessary aggressive management 
  • Mental distress

Screening Recommendation

  • Annual low-dose computed tomography (LDCT)
  • Patient selection based on organization recommendations:
    • The United States Preventive Services Task Force (USPSTF) 2020 recommends lung cancer screening for (must meet all criteria):
      • Adults aged 50‒80 years
      • Those with a 20-py smoking history
      • Current smoker or has quit within the past 15 years
    • The American Cancer Society recommends screening for (must meet all criteria):
      • Adults aged 55‒74 years
      • 30-py smoking history
      • Current smoker or quit within the past 15 years
    • Other organizations have similar recommendations, although the age range varies.
  • All patients in a screening program should receive smoking-cessation interventions.
  • Screening can be discontinued if the patient: 
    • Has not smoked for 15 years
    • Develops a health condition that will limit life expectancy
    • Is unable or unwilling to have curative lung surgery

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Strategies for Screening

Low-dose computed tomography

  • Demonstrated reduction in mortality in the National Lung Screening Trial (NLST):
    • 20% reduction in lung cancer mortality
    • 6.7% reduction in all-cause mortality
  • LDCT produces high-resolution images with less radiation.
  • Abnormal findings should be followed up with diagnostic computed tomography (CT).
  • Lung CT screening reporting and data system (Lung-RADS®)
    • Standardized-result reporting system
    • Designed to minimize the false-positive rate
Table: Summary of LDCT finding categories and guidance
CategoryAssessmentFollow-up
0IncompleteAwaiting prior CT images or images were technically inadequate
1Negative (no lung nodules)Continue normal annual screening.
2Benign-appearing nodule(s)Continue normal screening.
3Probably benign nodule(s)Repeat LDCT in 6 months.
4SuspiciousVaries and includes short-term follow-up LDCT, diagnostic CT, positron emission tomography, biopsy, or surgery

Chest radiograph

  • Previously used in combination with sputum cytology
  • Did not provide a mortality benefit
  • No longer recommended

References

  1. Deffebach, M.E., and Humphrey, L. (2020). Screening for lung cancer. UpToDate. Retrieved December 15, 2020, from https://www.uptodate.com/contents/screening-for-lung-cancer
  2. Midthun, David E., MD (2020). Clinical manifestations of lung cancer. UpToDate. Retrieved December 15, 2020, from https://www.uptodate.com/contents/overview-of-the-risk-factors-pathology-and-clinical-manifestations-of-lung-cancer
  3. McKee, B.J. (2019). Lung-RADS standardized reporting for low-dose computed tomography for lung cancer screening. UpToDate. Retrieved December 15, 2020, from https://www.uptodate.com/contents/lung-rads-standardized-reporting-for-low-dose-computed-tomography-for-lung-cancer-screening
  4. Keith, R.L. (2020). Lung carcinoma. MSD Manual Professional Version. https://www.msdmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma
  5. U.S. Preventive Services Task Force. (2020). Screening for lung cancer: U.S. Preventive Services Task Force draft recommendation statement. https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/lung-cancer-screening1
  6. Siddiqui, F., and Siddiqui, A.H. (2020). Lung cancer. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK482357/
  7. Tindle, H. A., Stevenson Duncan, M., Greevy, R. A., Vasan, R. S., Kundu, S., Massion, P. P., & Freiberg, M. S. (2018). Lifetime smoking history and risk of lung cancer: Results from the framingham heart study. JNCI: Journal of the National Cancer Institute, 110(11), 1201–1207. https://doi.org/10.1093/jnci/djy041
  8. Markaki, M., Tsamardinos, I., Langhammer, A. et al. (2018). A Validated Clinical Risk Prediction Model for Lung Cancer in Smokers of All Ages and Exposure Types: A HUNT Study. / EBioMedicine, 31(2018), 36–46. https://www.thelancet.com/action/showPdf?pii=S2352-3964%2818%2930114-2
  9. Pleasants, R.A, Rivera, M.P., Tilley, S.L., Bhatt, S.P. (2020). Both Duration and Pack-Years of Tobacco Smoking Should Be Used for Clinical Practice and Research. Annals of the American Thoracic Society, 17(7), 804–806. https://doi.org/10.1513/AnnalsATS.202002-133VP 
  10. ELF. Lung cancer. Retrieved December 15, 2020, from https://www.europeanlung.org/en/projects-and-research/projects/smokehaz/lung-conditions/home/adults/lung-cancer/active-smoking/detailed-findings-and-data
  11. CDC. (2020). Smoking and Cancer. https://www.cdc.gov/tobacco/campaign/tips/diseases/cancer.html
  12. Kumar, V., Abbas, A. K., Aster, J.C., (Eds.) (2020). Effects of Tobacco. Robbins & Cotran Pathologic Basis of Disease. (10 ed. pp. 415–418).

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