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Non-small cell lung cancer

  • Overview
  • Theory
  • Diagnosis
  • Management
  • Follow up
  • Resources
Last reviewed: 1 Jun 2025
Last updated: 15 May 2025

Summary

Definition

History and exam

Key diagnostic factors

  • cough
  • dyspnea
  • hemoptysis
  • chest and/or shoulder pain
  • weight loss
Full details

Other diagnostic factors

  • male sex
  • fatigue
  • pulmonary exam abnormalities
  • hoarseness
  • confusion
  • personality changes
  • nausea and vomiting
  • headache
  • dysphagia
  • bone pain and/or fractures
  • weakness, paresthesias, and/or pain in C8/T1 distribution
  • seizures
  • cervical or supraclavicular adenopathy
  • Horner syndrome
  • facial swelling
  • dilated neck or chest/abdominal wall veins
  • finger clubbing
  • hypertrophic pulmonary osteoarthropathy
Full details

Risk factors

  • cigarette smoking
  • environmental tobacco exposure
  • chronic obstructive pulmonary disease (COPD)
  • family history
  • radon gas exposure
  • older age
  • asbestos exposure
Full details

Diagnostic tests

1st tests to order

  • chest x-ray
  • contrast-enhanced CT scan of lower neck, thorax, and upper abdomen
Full details

Tests to consider

  • sputum cytology
  • bronchoscopy
  • biopsy
  • diagnostic thoracentesis and/or pleural biopsy
  • sampling of the mediastinal lymph nodes: mediastinoscopy and endobronchial ultrasound (EBUS)
  • video-assisted thoracoscopic surgery (VATS)
  • thoracoscopy
  • MRI or CT of brain
  • MRI of thoracic inlet
  • CT with contrast and/or fluorodeoxyglucose (FDG)-PET
  • bone scan
  • contrast-enhanced CT liver and adrenals
  • pulmonary function tests (PFT)
  • CBC
  • LFTs
  • serum calcium
  • electrolytes and renal function
  • electrocardiogram and echocardiogram
  • epidermal growth factor receptor (EGFR) mutation testing
  • anaplastic lymphoma kinase (ALK) testing
  • ROS proto-oncogene 1 (ROS1) testing
  • programmed death-ligand 1 (PD-L1) testing
  • B-Raf proto-oncogene (BRAF) testing
  • neurotrophin tyrosine receptor kinase (NTRK) fusion testing
  • Mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping mutations
  • rearranged during transfection (RET) gene mutations testing
  • KRAS proto-oncogene (KRAS) point mutations testing
  • ERBB2 (HER2) mutations testing
Full details

Treatment algorithm

ONGOING

stage I and II

stage IIIA

stage IIIB and IIIC

stage III with tumors too extensive for combination chemoradiation therapy or stage IV and suitable for immunotherapy or targeted therapy

stage III with tumors too extensive for combination chemoradiation therapy or stage IV and unsuitable for immunotherapy or targeted therapy (ECOG performance 0-2)

stage III with tumors too extensive for combination chemoradiation therapy or stage IV and unsuitable for immunotherapy or targeted therapy (ECOG performance 3-4)

Contributors

Authors

Alex A. Adjei, MD, PhD, FACP

Chairman, Taussig Cancer Institute

M. Frank Rudy and Margaret Domiter Rudy Distinguished Chair in Translational Cancer Research

Cleveland Clinic

Cleveland

OH

Disclosures

AAA declares that he has no competing interests.

Dr Fen Wang, MD

Peking University Shenzhen Hospital

Shenzhen

Guangdong

China

Disclosures

FW declares that she has no competing interests.

Acknowledgements

Professor Alex A. Adjei and Dr Fen Wang would like to gratefully acknowledge Professor David R. Baldwin, Dr Sanjay Popat, Dr Mick Peake, Dr Chris Kelsey, and Dr Lawrence Marks, previous contributors to this topic.

Disclosures

DRB declares that he has no competing interests. SP has been paid and acted as a consultant to BMS, Eli Lilly, Roche, Takeda, AstraZeneca, Chugai, Novartis, Pfizer, MSD, EMD Serono, Guardant Health, AbbVie, Boehringer Ingelheim, and Tesaro; SP has received research grants from Pierre Fabre, Otsuka, and Boehringer Ingelheim; SP has received assistance for travel from Boehringer Ingelheim, MSD, and Pfizer. MP has received lecture fees from AstraZeneca Pharmaceuticals, Lilly Oncology Ltd, Pierre-Fabre, GSK Ltd, and Roche Pharmaceuticals Ltd; MP has also received educational grants to attend scientific conferences from Roche Pharmaceuticals Ltd and Boehringer Ingelheim Ltd. CK and LM declare that they have no competing interests.

Peer reviewers

Alan Neville, MD

Professor

Assistant Dean

Undergraduate Program

McMaster University

Hamilton

Ontario

Canada

Disclosures

AN declares that he has no competing interests.

James Huang, MD

Assistant Attending Surgeon

Thoracic Service

Memorial Sloan Kettering Cancer Center

New York

NY

Disclosures

JH declares that he has no competing interests.

Siow Ming Lee, PhD, FRCP

Consultant Medical Oncologist

University College Hospital

London

UK

Disclosures

SML declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

National Institute for Health and Care Excellence. Lung cancer: diagnosis and management. March 2024 [internet publication].Full text

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer [internet publication].Full text

European Society for Medical Oncology. Oncogene-mediated metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Jan 2023 [internet publication].Full text

Hendriks L E, Kerr K, Menis J, et al. on behalf of the ESMO Guidelines Committee. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Jan 2023;34(4):358-76.Full text

Bazhenova L, Ismaila N, Abu Rous F, et al. Therapy for stage IV non-small cell lung cancer with driver alterations: ASCO living guideline, version 2024.2. J Clin Oncol. 2024 Dec 20;42(36):e72-86.Full text  Abstract

Jaiyesimi IA, Leighl NB, Ismaila N, et al. Therapy for stage IV non-small cell lung cancer without driver alterations: ASCO living guideline, version 2023.3. J Clin Oncol. 2024 Apr 10;42(11):e23-43.Full text  Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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