Non-small cell lung cancer

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 28 Feb 2025

Last updated: 28 Oct 2024

Non-small cell lung cancer is most common in older adult smokers and ex-smokers. Small tumors in the lung are often asymptomatic, so the majority of patients have either locally advanced or metastatic disease at diagnosis.

Most common presenting symptoms are cough, chest pain, hemoptysis, dyspnea, and weight loss.

A suspicious lung mass can be biopsied during bronchoscopy or using CT guidance. Staging studies (i.e., CT, PET, mediastinal sampling) are required to determine extent of local or regional disease and to evaluate for metastases.

Treatment depends on stage of disease, histologic subtype, molecular genotype, and patient comorbidities. Treatment modalities include surgery, radiation therapy, and chemotherapy, as well as molecular-targeted therapy for specific genotypes and immunotherapy.

Definition

Lung cancer comprises a group of malignant epithelial tumors arising from cells lining the lower respiratory tract. Lung cancer is divided into two categories: non-small cell lung cancer (NSCLC) and small cell lung cancer. NSCLC accounts for more than 80% of all lung cancers.[1] There are three main types of NSCLC (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma) and these are grouped into further subtypes.

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

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

Disclosures

JH declares that he has no competing interests.

Siow Ming Lee, PhD, FRCP

Consultant Medical Oncologist

University College Hospital

London

Disclosures

SML declares that he has no competing interests.

Differentials
- Small cell lung cancer
- Metastatic cancer
- Pneumonia/bronchitis
More Differentials
Guidelines
- Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO living guideline
- Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO living guideline
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Patient information
Lung cancer (non-small-cell)
Lung cancer: questions to ask your doctor
More Patient information
Videos
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Non-small cell lung cancer

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

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

Disclosures

Dr Fen Wang, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Alan Neville, MD

Disclosures

James Huang, MD

Disclosures

Siow Ming Lee, PhD, FRCP

Disclosures

Differentials

Guidelines

Patient information

Videos

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