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Last reviewed: 16 Mar 2025
Last updated: 15 Apr 2025

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • cough
  • dyspnoea
  • haemoptysis
  • chest and/or shoulder pain
  • weight loss

Other diagnostic factors

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

Risk factors

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

Diagnostic investigations

1st investigations to order

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

Investigations 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)
  • FBC
  • 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
  • re-arranged during transfection (RET) gene mutations testing
  • KRAS proto-oncogene (KRAS) point mutations testing
  • ERBB2 (HER2) mutations testing

Treatment algorithm

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.

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