Lung cancer overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammad Braizat, M.S. [2]

Lung cancer is a malignant epithelial tumor of the lung that is not a single disease but two biologically and therapeutically distinct entities: non–small cell lung cancer (NSCLC, ~85%) and small cell lung cancer (SCLC, ~15%).^[1][2] The single most important change from legacy teaching is that lung cancer is no longer managed as one disease: histologic subtype, molecular driver status, and PD-L1 expression now dictate therapy in advanced disease, and low-dose CT (LDCT) screening plus stage-shift have begun to bend the mortality curve.^[3][4]

This microchapter covers risk factors and relevant contextual data for lung cancer. Definition, classification, epidemiology, screening, diagnosis, staging, treatment, and prognosis are summarized only as needed for context and are detailed in their dedicated microchapters.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide — approximately 2.48 million new cases and 1.8 million deaths in 2022, with the global burden projected to rise toward 4.6 million cases and 3.5 million deaths by 2050 absent intervention.^[5][6] In the US it remains the leading cause of cancer death despite falling incidence.^[7] US lung cancer death rates are declining faster than incidence; the ACS reports the 2014–2020 mortality decline accelerated to approximately −5.3%/year in men and −4.3%/year in women, reflecting reduced smoking, earlier-stage diagnosis, and improved therapy.^[8] Detailed demographics and secular trends belong in the Epidemiology microchapter.

Cigarette smoking is the single most important cause of lung cancer, accounting for roughly 80–90% of cases and an ~85% population-attributable fraction in the US, with a 10- to 30-fold (≈20-fold) relative risk versus never-smokers.^[9][10][11] Risk rises with cumulative exposure in a nonlinear dose-response: mean relative risk ≈5.1 at 20 pack-years and ≈13.4 at ~51 pack-years, with diminishing marginal risk beyond ~40 pack-years.^[12] Risk declines with sustained cessation.^[9][12] Cigars, pipes, and bidis also cause lung cancer.^[9]

Living with a person who smokes increases non-smoker risk by ~20–30% and is responsible for an estimated ~3,500 US non-smoker lung cancer deaths annually (~2.7% of US lung cancer cases).^[9][10]

Radon is the second-leading cause overall and the leading environmental cause in never-smokers (~12% of US lung cancers; up to ~21,000 deaths/year).^[13][10] The EPA recommends mitigation at ≥4 pCi/L (150 Bq/m³) and consideration between 2–4 pCi/L.^[10]

Established occupational carcinogens include asbestos, arsenic, chromium, nickel, beryllium, cadmium, silica dust, diesel exhaust, and ionizing radiation; several act independently of and multiplicatively with smoking.^[9][11] Ambient air pollution (PM2.5; IARC group 1) and household solid-fuel/cooking-oil fumes are additional contributors, particularly in never-smoking women.^[13][10]

Family history of lung cancer in a first-degree relative confers an ~2–4× risk. COPD, pulmonary fibrosis, prior thoracic radiotherapy, East Asian female ancestry, and germline variants also increase risk.^[11][13][14] Approximately 15–25% of lung cancers occur in never-smokers, a growing proportion, with higher rates of targetable EGFR and ALK alterations.^[13][15][14]

Annual LDCT screening is recommended for eligible high-risk adults (USPSTF Grade B: age 50–80 years, ≥20 pack-years, currently smoking or quit within 15 years). Eligibility thresholds, Lung-RADS management, and shared decision-making belong in the Screening microchapter.^[4][8]

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