Lung, Primary Malignancies
Basics
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
- Non–small cell lung cancer (NSCLC) (85% of all lung cancers)
- 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
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Citation
Domino, Frank J., et al., editors. "Lung, Primary Malignancies." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116357/2.1/Lung_Primary_Malignancies.
Lung, Primary Malignancies. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116357/2.1/Lung_Primary_Malignancies. Accessed October 11, 2024.
Lung, Primary Malignancies. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116357/2.1/Lung_Primary_Malignancies
Lung, Primary Malignancies [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 October 11]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116357/2.1/Lung_Primary_Malignancies.
* Article titles in AMA citation format should be in sentence-case
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ED - Stephens,Mark B,
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