Description

• Leading cause of cancer-related death in the US (estimated 160,340 deaths in 2012, 28% of all cancer-related deaths) (1)
• Divided into 2 broad categories:
  • Non–small-cell lung cancer (NSCLC) (>85% of all lung cancers):
    • Adenocarcinoma (~40% of NSCLC): Most common type in the US, most common type in nonsmokers, metastasizes earlier than squamous cell, poor prognosis; bronchoalveolar, a subtype of adenocarcinoma has better prognosis
    • Squamous cell 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
• Other: Mesothelioma, carcinoid tumor, and sarcoma
• Staging:
  • NSCLC: Staged from 0–IV based on: Primary tumor (T), lymph node status (N), and presence of metastasis (M)
  • SCLC: Staged based on disease location: Limited to ipsilateral hemithorax (stages I–IIIB); extensive if metastatic beyond hemithorax (stages IIIB and IV)
• Tumor locations: Upper: 60%; lower: 30%; middle: 5%; overlapping and main stem: 5%
• May spread by local extension to involve chest wall, diaphragm, pulmonary vessels, vena cava, phrenic nerve, esophagus, or pericardium
• Most commonly metastasize to lymph nodes (pulmonary, mediastinal), then liver, adrenal, bone (osteolytic), kidney, brain

Epidemiology

• Estimated 226,160 new cases in the US in 2012 (1)
• Predominant age: >40 years; peak at 70 years
• Predominant sex: Male > Female

• Most common cancer worldwide
• Lifetime probability (1):
  • Men: 1 in 13
  • Women: 1 in 16

Risk Factors

• Smoking (relative risk [RR] 10–30)
• Second-hand smoke exposure
• Radon
• Environmental and occupational exposures:
  • Asbestos exposure (synergistic increase in risk for smokers)
  • Air pollution
  • 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

• Oncogenes: Ras family (H-ras, K-ras, N-ras)
• Tumor suppressor genes: Retinoblastoma, p-53

General Prevention

• Screening controversial; the risks of screening (e.g., radiation, biopsy) may offset the benefit.
• Consider for high-risk patients, but best approach remains unclear:
  • High-risk patients: Age 55–74 years with a ≥30-pack year history of smoking tobacco, or if a former smoker, quit within 15 years
  • Annual low-dose CT until age 74 years:
    • Decreased lung cancer mortality (but not life expectancy) compared with chest x-ray alone (2)
• Prevention via aggressive smoking-cessation counseling and therapy; a 20–30% risk reduction occurs within 5 years of cessation
• Avoid supplemental β-carotene and vitamin E in smokers
• Avoid hormone replacement therapy in postmenopausal smokers or former smokers (increased risk of death from NSCLC)

Etiology

Multifactorial; see “Risk Factors.”

Commonly Associated Conditions

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