Description

• Primary lung cancers are the leading cause of cancer-related deaths in the United States (estimated 130,180 deaths in 2021 which accounts for 25% of all cancer-related deaths). Lung cancer is mainly diagnosed in older people at average age of diagnosis at 70 years. Lung cancer has the lowest 5-year survival rate at only 18% compared to breast cancer at 90%, prostate cancer at 99%, and colorectal cancer at 65%. Vast majority (85%) of lung cancer is due to smoking, whereas the other 15% is caused by genetics, second hand smoking, asbestos, radon, and other air pollution.
• Divided into two broad categories
  • Non–small cell lung cancer (NSCLC) (85% of all lung cancers)
    • Adenocarcinoma (~40% of NSCLC): most common type in the United States and occurs in both smokers and nonsmokers; metastasizes earlier than squamous cell; usually starts from peripheral lung tissue
    • Squamous cell carcinoma (SCC) (30% of NSCLC) usually occurs close to large airways.
    • Large cell (~10% of NSCLC): named because of the cells’ large nuclei
  • Small cell lung cancer (SCLC) (15% of all lung cancers): centrally located, aggressive, and metastasizes very easily through the blood seeding lymph nodes, bones, brain, adrenals, and liver
• 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)
    • Most commonly metastasize to lymph nodes (pulmonary, mediastinal) and then liver, adrenal glands, bones, brain

Epidemiology

Incidence

• There are 236,000 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.
• Average age of diagnosis: 70 years old
• Due to decreases in smoking, lung cancer deaths are declining in the United States.

Etiology and Pathophysiology

Genetics
NSCLC

• Oncogenes: Ras family (H-ras, K-ras, N-ras), EGFR, NTRK, ALK, etc.
• Tumor suppressor genes: retinoblastoma, p53
• Genetics accounts for 8% of lung cancers.

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
• 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 (1).
• 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.

Commonly Associated Conditions

• Paraneoplastic syndromes: hypertrophic pulmonary osteoarthropathy, Lambert-Eaton syndrome (LES), Cushing syndrome, hypercalcemia from ectopic parathyroid hormone–related protein (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