Non-small cell lung cancer

Last reviewed: 6 May 2023
Last updated: 25 Oct 2022



History and exam

Key diagnostic factors

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

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
Other diagnostic factors

Risk factors

  • cigarette smoking
  • environmental tobacco exposure
  • chronic obstructive pulmonary disease
  • family history
  • radon gas exposure
  • older age
  • asbestos exposure
More risk factors

Diagnostic investigations

1st investigations to order

  • chest x-ray
  • contrast-enhanced CT scan of lower neck, thorax, and upper abdomen
More 1st investigations to order

Investigations to consider

  • sputum cytology
  • bronchoscopy
  • biopsy
  • diagnostic thoracentesis and/or pleural biopsy
  • sampling of the mediastinal lymph nodes: mediastinoscopy and endobronchial ultrasound
  • video-assisted thoracoscopic surgery (VATS)
  • thoracoscopy
  • MRI or CT of brain
  • MRI of thoracic inlet
  • PET-CT
  • 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
  • c-Mesenchymal-epithelial transition factor (c-MET) exon 14 (METex14) skipping mutations testing
  • rearranged during transfection (RET) gene mutations testing
  • KRAS proto-oncogene (KRAS) point mutations testing
More investigations to consider

Treatment algorithm


stage I and II

stage IIIA

stage IIIB and IIIC

stage III with tumours too extensive for combination chemoradiotherapy or stage IV and suitable for immunotherapy or targeted therapy

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

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



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




AAA has acted as an uncompensated advisory board member for Swiss Rockets, Merck AG, and Zai Lab.

Dr Fen Wang, MD

Peking University Shenzhen Hospital





FW declares that she has no competing interests


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.


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


Assistant Dean

Undergraduate Program

McMaster University





AN declares that he has no competing interests.

James Huang, MD

Assistant Attending Surgeon

Thoracic Service

Memorial Sloan Kettering Cancer Center

New York



JH declares that he has no competing interests.

Siow Ming Lee, PhD, FRCP

Consultant Medical Oncologist

University College Hospital




SML declares that he has no competing interests.

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