Description

• Primary lung cancers are the leading cause of cancer-related deaths in the United States (estimated 154,050 deaths in 2018, 25.3% of all cancer-related deaths).
• Divided into two broad categories
  • Non–small cell lung cancer (NSCLC) (>85% of all lung cancers); normally originate in periphery
    • Adenocarcinoma (~40% of NSCLC): most common type in the United States and occurs in both smokers and nonsmokers; metastasizes earlier than squamous cell; lepidic growth, a subtype of adenocarcinoma has better prognosis.
    • Squamous cell carcinoma (SCC) (also known as epidermoid carcinoma) (~25% of NSCLC): dose-related effect with smoking; slower growing than adenocarcinoma
    • Large cell (~10% of NSCLC): prognosis similar to adenocarcinoma
  • Small cell lung cancer (SCLC) (16% of all lung cancers): centrally located, early metastases, aggressive
• Others: mesothelioma and carcinoid tumor
• Staging
  • Both NSCLC and SCLC: staged from I to IV based on: primary tumor (T), lymph node status (N), and presence of metastasis (M)
  • SCLC further staged by:
    • Limited disease: confined to ipsilateral hemithorax
    • Extensive disease: beyond ipsilateral hemithorax (stages IIIB and IV), which may include malignant pleural or pericardial effusion or hematogenous metastases (stage IV)
    • Tumor locations: upper: 60%; lower: 30%; middle: 5%; overlapping and main stem: 5%
    • May spread by local extension to chest wall, diaphragm, pulmonary vessels, vena cava, phrenic nerve, esophagus, or pericardium
    • Most commonly metastasize to lymph nodes (pulmonary, mediastinal), then liver, adrenal glands, bones, brain

Epidemiology

Incidence

• There are >230,000 new cases of lung cancer and 130,000 deaths annually in the United States in 2021.
• Overall, lung cancer causes more deaths than breast, prostate, colorectal, and brain cancers combined.
• Usual age of diagnosis: between 65 and 74 years; peak at 70 years
• Due to decreases in smoking, lung cancer deaths are declining in both men and women.
• Nearly one-half of all lung cancer deaths occur in women.

Prevalence

• Mortality from SCLC declined almost entirely as a result of declining incidence, with no improvement in survival
• Population-level mortality from NSCLC in the United States fell sharply from 2013 to 2016, and survival after diagnosis improved substantially.

Etiology and Pathophysiology

Multifactorial; see “Risk Factors.”

Genetics
NSCLC

• Oncogenes: Ras family (H-ras, K-ras, N-ras), EGFR, NTRK, ALK, etc.
• Tumor suppressor genes: retinoblastoma, p53

Risk Factors

• Smoking
• Secondhand smoke exposure
• Radon
• Environmental and occupational exposures
  • Air pollution
  • Asbestos exposure (synergistic increase in risk for smokers)
  • Ionizing radiation
  • Mutagenic gases (halogen ethers, mustard gas, aromatic hydrocarbons)
  • Metals (inorganic arsenic, chromium, nickel)
• Lung scarring from tuberculosis
• Radiation therapy to the breast or chest

General Prevention

• Smoking cessation and prevention programs
• Screening recommended by National Comprehensive Cancer Network (NCCN) and shown to reduce mortality in National Lung Screening Trial (NLST) (1)[A].
• As of March 9, 2021, the USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (2).
• 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.
• Prevention via aggressive smoking cessation counseling and therapy; a 20–30% risk reduction occurs within 5 years of cessation.

Commonly Associated Conditions

• Paraneoplastic syndromes: hypertrophic pulmonary osteoarthropathy, Lambert-Eaton syndrome (LES), Cushing syndrome, hypercalcemia from ectopic parathyroid-releasing hormone (PTHrP), syndrome of inappropriate antidiuretic hormone (SIADH)
• Hypercoagulable state
• Pancoast syndrome
• Superior vena cava (SVC) syndrome
• Pleural effusion
• Chronic obstructive pulmonary disease (COPD), other sequelae of cigarette smoking