Lung, Primary Malignancies

Descriptive text is not available for this image BASICS

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. It has the lowest 5-year survival rate (~18% vs breast cancer at 91%, prostate cancer at 99%, and colorectal cancer at 65%). 85% of lung cancer is due to smoking; remaining 15% is caused by radon exposure, genetics, second-hand smoke, asbestos, and other air pollution.

DESCRIPTION

  • Two broad categories
    • Non–small cell lung cancer (NSCLC) accounts for 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): accounts for 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): accounts for 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, carcinoid tumor

EPIDEMIOLOGY

Incidence

  • There were 209,500 new cases of lung cancer in 2021 and 131,888 deaths in the United States in 2022 (CDC).
  • Male patients had both higher rates (54.1 versus 45.5 per 100,000) and higher chance of death (35.2 versus 25.9 per 100,000) compared to females.
  • 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

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

RISK FACTORS

  • Smoking
  • Secondhand smoke exposure
  • Radon
  • Environmental/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 breast or chest

GENERAL PREVENTION

  • Smoking cessation and prevention programs
  • 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-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

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