Lung Cancer Screening (Clinical)

Overview

Lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer^[1,4-6]

Lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer is a malignant tumor Tumor Inflammation of the lung originating from the respiratory epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology of the bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy, bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy, and alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS).

Epidemiology^[1,2,4-8]

• Lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. 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 Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency increases with age:
  • Rare under the age of 50 years
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency peaks at ages 75–79 years.
• 85%‒90% of lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer cases are attributed to smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases.

Risk factors^[1,4-7,10]

• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (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 Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases at a lower intensity for a long time: more likely to develop lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer than smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases at a higher intensity for a shorter time
  • The association with electronic cigarettes is not yet clear.
• Environmental exposures:
  • 2nd-hand smoke
  • Air pollution Pollution The presence of contaminants or pollutant substances in the air (air pollutants) that interfere with human health or welfare, or produce other harmful environmental effects. The substances may include gases; particulate matter; or volatile organic chemicals. Asthma
  • Asbestos
  • Radon Radon A naturally radioactive element with atomic symbol Rn, and atomic number 86. It is a member of the noble gas family found in soil, and is released during the decay of radium. Squamous Cell Carcinoma (SCC)
  • Chromium Chromium A trace element that plays a role in glucose metabolism. It has the atomic symbol cr, atomic number 24, and atomic weight 52. According to the fourth annual report on carcinogens, chromium and some of its compounds have been listed as known carcinogens. Trace Elements
  • Nickel
  • Arsenic Arsenic A shiny gray element with atomic symbol as, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the fourth annual report on carcinogens, arsenic and certain arsenic compounds have been listed as known carcinogens. Metal Poisoning (Lead, Arsenic, Iron)
  • Polycyclic aromatic hydrocarbons
• Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma treatment
• Lung disease:
  • Idiopathic Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
  • Alpha-1 antitrypsin Alpha-1 antitrypsin Plasma glycoprotein member of the serpin superfamily which inhibits trypsin; neutrophil elastase; and other proteolytic enzymes. Alpha-1 Antitrypsin (AAT) Deficiency deficiency
  • Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
• Human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HIV HIV Anti-HIV Drugs) infection
• Family history Family History Adult Health Maintenance
• Alcohol consumption

Risk factor reduction^[4,7,11]

Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation reduces the risk of lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. 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 Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases also lowers the risk for other diseases/conditions (such as other cancers, atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis, and chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis).

Screening Rationale

Benefits of screening Screening Preoperative Care^[1,4,5]

• Goal is to detect early disease, which is:
  • More amenable to treatment
  • Associated with better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
• Several studies also show a favorable association with smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation.

Risks of screening Screening Preoperative Care^[1,13,14]

• High false-positive rate
• Most abnormalities detected are benign nodules Benign Nodules Thyroid Nodules.
• Leads to unnecessary biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma or surgery
• Increased radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma exposure
• Overdiagnosis:
  • Detection of cancers that would not have affected morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status or mortality Mortality All deaths reported in a given population. Measures of Health Status for the patient
  • Leads to unnecessary aggressive management 
• Mental distress
• Financial burden

Screening Recommendation

• Annual low-dose computed tomography Low-Dose Computed Tomography Lung Cancer Screening ( LDCT LDCT Lung Cancer Screening)^[4,13,14]
• Patient selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions based on organization recommendations:
  • The United States Preventive Services Task Force (USPSTF) 2021 recommends lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer screening Screening Preoperative Care for (must meet all criteria):^[4]
    • Adults aged 50‒80 years
    • Those with a 20-py smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases history
    • Current smoker or has quit within the past 15 years
  • The American Cancer Society recommends screening Screening Preoperative Care for (must meet all criteria):^[19]
    • Adults aged 55‒74 years
    • 30-py smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases history
    • Current smoker or quit within the past 15 years
  • Other organizations have similar recommendations, although the age range varies; Centers for Medicare and Medicaid Services generally have similar recommendations set out by the USPSTF.^[16]
    • Adults ages 50‒77 years
    • Asymptomatic
    • ≥ 20-py smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases history
    • Current smoker or quit within the past 15 years
• Risk calculators may assist in determining high-risk candidates who do not fit the above criteria, such as:
  • Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial:^[20,21] estimates 6-year lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer risk
  • Liverpool Lung Project (LLP) risk model^[22]
• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in a screening Screening Preoperative Care program should receive smoking-cessation interventions.
• Screening Screening Preoperative Care can be discontinued if the patient:^[14]
  • Is > 81 years of age
  • Has not smoked for ≥ 15 years
  • Develops a health condition that will limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids
  • Is unable or unwilling to have curative lung surgery
• If the patient is symptomatic (cough, hoarseness Hoarseness An unnaturally deep or rough quality of voice. Parapharyngeal Abscess, unexpected weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, or hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis), proceed with diagnostic evaluation.

Strategies for Screening

Low-dose computed tomography Low-Dose Computed Tomography Lung Cancer Screening

• Demonstrated reduction in mortality Mortality All deaths reported in a given population. Measures of Health Status in the National Lung Screening Trial National Lung Screening Trial Lung Cancer Screening ( NLST NLST Lung Cancer Screening):^[4,13,14,17]
  • 20% reduction in lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer mortality Mortality All deaths reported in a given population. Measures of Health Status
  • 6.7% reduction in all-cause mortality Mortality All deaths reported in a given population. Measures of Health Status
• LDCT LDCT Lung Cancer Screening produces high-resolution images with less radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma.
• Abnormal findings should be followed up with diagnostic computed tomography (CT).
• Lung CT screening Screening Preoperative Care reporting and data system ( Lung-RADS Lung-RADS Standardized-result reporting system designed to minimize the false-positive rate Lung Cancer Screening®)^[18]
  • Standardized-result reporting system
  • Designed to minimize the false-positive rate

Chest radiography^[17]

• Previously used in combination with sputum cytology
• Did not provide a mortality Mortality All deaths reported in a given population. Measures of Health Status benefit
• No longer recommended