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.
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. 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
- chest and/or shoulder pain
- weight loss
Other diagnostic factors
- male sex
- pulmonary exam abnormalities
- personality changes
- nausea and vomiting
- bone pain and/or fractures
- weakness, paresthesias, and/or pain in C8/T1 distribution
- cervical or supraclavicular adenopathy
- Horner syndrome
- facial swelling
- dilated neck or chest/abdominal wall veins
- finger clubbing
- hypertrophic pulmonary osteoarthropathy
- cigarette smoking
- environmental tobacco exposure
- chronic obstructive pulmonary disease
- family history
- radon gas exposure
- older age
- asbestos exposure
1st investigations to order
- chest x-ray
- contrast-enhanced CT scan of lower neck, thorax, and upper abdomen
Investigations to consider
- sputum cytology
- diagnostic thoracentesis and/or pleural biopsy
- sampling of the mediastinal lymph nodes: mediastinoscopy and endobronchial ultrasound
- video-assisted thoracoscopic surgery (VATS)
- MRI or CT of brain
- MRI of thoracic inlet
- bone scan
- contrast-enhanced CT liver and adrenals
- pulmonary function tests (PFT)
- 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
stage I and II
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)
Alex A. Adjei, MD, PhD, FACP
Chairman, Taussig Cancer Institute
M. Frank Rudy and Margaret Domiter Rudy Distinguished Chair in Translational Cancer Research
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.
Alan Neville, MD
AN declares that he has no competing interests.
James Huang, MD
Assistant Attending Surgeon
Memorial Sloan Kettering Cancer Center
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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