Non–small-cell lung cancer

By Megan Lee. Updated by Laura Boyd

Non–small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80–85% of cases.¹ It comprises multiple histological subtypes and is characterized by molecular heterogeneity, enabling biomarker-driven treatment approaches.² 

What are the key risk factors associated with NSCLC?

Smoking is the leading risk factor for NSCLC; however, approximately 15% of cases occur in “never-smokers”.³ Additional risk factors include environmental exposures, occupational carcinogens, and genetic susceptibility.^3,4

What are the main histological subtypes of NSCLC?

NSCLC includes three primary histological subtypes: adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma, with adenocarcinoma most common in “never-smokers”.^4,5 These subtypes are identified through histological assessment of tumor biopsy, with molecular testing used to define actionable alterations and guide treatment.⁴

How is NSCLC classified and staged?

NSCLC is staged using the tumor node metastasis (TNM) system, assessing tumor size and extent (T), lymph node involvement (N), and distant metastasis (M).⁶ This supports prognostic stratification, with early-stage disease confined to the lung and advanced disease reflecting regional or distant spread.⁷

What are current treatment approaches?

Treatment depends on disease stage and molecular profile. Early-stage NSCLC is primarily managed with surgical resection and adjuvant therapy,⁸ while locally advanced disease is treated with chemoradiotherapy, often followed by immunotherapy.⁹ Advanced disease is managed with targeted therapies for actionable mutations or immunotherapy (with or without chemotherapy) in biomarker‑selected populations.^9,10

References

1. Padinharayil, 2023. Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics. https://www.doi.org/10.1016/j.gendis.2022.07.023
2. Steinestel, 2025. Current biomarkers in non-small cell lung cancer: The molecular pathologist’s perspective. https://www.mdpi.com/2075-4418/15/5/631
3. Murphy, 2025. Lung cancer in nonsmoking individuals: A review. https://www.doi.org/10.1001/jama.2025.17695
4. Alduais, 2023. Non-small cell lung cancer (NSCLC): A review of risk factors, diagnosis, and treatment. https://www.doi.org/10.1097/MD.0000000000032899
5. Paik, 2026. Squamous non-small cell lung cancer: Current and emerging treatment options. https://www.doi.org/10.1016/j.cllc.2025.10.001
6. Kuhtić, 2025. Clinical TNM lung cancer staging: A diagnostic algorithm with a pictorial review. https://www.doi.org/10.3390/diagnostics15070908
7. Kahya, 2026. Breaking: The new 9(th) version TNM classification for lung cancer is now in use. https://www.doi.org/10.4274/ThoracResPract.2025.2025-2-6
8. Allehebi, 2022. Management of early-stage resected non-small cell lung cancer: Consensus statement of the Lung Cancer Consortium. https://www.doi.org/10.1016/j.ctarc.2022.100538
9. 2025. Non-small cell lung cancer treatment (PDQ^®). https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#top
10. ACS, 2025. Treatment choices for non-small cell lung cancer, by stage. https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/by-stage.html

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