Background Information

Definitions

Lung cancer (historically termed bronchogenic carcinoma): malignant neoplasm arising from epithelial cells of the lower respiratory tract, most commonly of the bronchi or alveoli. It is classified into two major histologic types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). ^[Ref]

• NSCLC (~85% of cases)​​​​​​: Includes three principal histologic subtypes
  • Adenocarcinoma → Most common subtype of lung cancer
  • Squamous cell carcinoma
  • Large cell carcinoma
• SCLC (~15% of cases)

Epidemiology

Incidence ^[Ref]

• 2nd most common cancer (after breast/prostate in females/males)
• Leading cause of cancer-related death
• Incidence is overall greater in males
  • Except for adenocarcinoma, which is more common in women

Age → peak 65-74 yrs ^[Ref]

Risk Factors

Tobacco smoking → most significant risk factor 

• Strongly associated with squamous cell & small cell carcinoma ^[Ref]
• Weaker association with adenocarcinoma (commonest lung cancer in non-smokers)

Non-smoking-related risk factors 

• Secondhand smoke
• Air pollution
• Radon / Uranium exposure
• Prior chest radiation
• Occupational carcinogens (e.g., arsenic, chromium, beryllium)
• Family History (genetic risk factors)​​​

Clinical features

General

Systemic effects of malignancy (similar across all subtypes)

• Weight loss
• Anorexia
• Fatigue
• Fever

Pulmonary

Typical

• Cough (most frequent)
• Haemoptysis
• Dyspnoea
• Recurrent / persistent respiratory infections
• Chest pain

Peripheral lesions (adenocarcinoma / large cell carcinoma) may cause:

• Pleuritic pain OR pleural effusion

 

Extrapulmonary

Tumour mass effects can give rise to a variety of extrapulmonary symptoms: ^[Ref]

1) Superior vena cava syndrome

• Definition → venous congestion of the head, neck and upper extremities resulting from impaired venous drainage of the superior vena cava; can occur through both intraluminal & extraluminal obstruction in malignancy.

 

• More common with central tumours (e.g., SCLC, SCC)

 

• Features
  • Facial and neck swelling (early)
  • Venous distention of the neck/chest wall
  • Respiratory compromise → dyspnoea / cough to stridor / hoarseness
  • Neurologic symptoms → headache, dizziness, confusion

2) Hoarseness → paralysis/compression of the recurrent laryngeal nerve 

3) Dysphagia → oesophageal compression

4) Pancoast syndrome

• Definition: constellation of findings related to compression of chest wall structures, particularly at the level of the 1st rib and above, by apical lung cancers (aka pancoast or superior sulcus tumours)

 

• Affected chest wall structures:
  • Stellate ganglion (cervical sympathetic ganglion) → Horner syndrome (ipsilateral miosis, ptosis and anhidrosis)
  • Brachial plexus → shoulder / arm pain, upper limb motor and sensory deficits
  • Subclavian vein → upper limb oedema
  • Recurrent laryngeal nerve → hoarseness
  • Phrenic nerve → hemidaphragm paralysis (elevated on CXR)

 

• The classic Pancoast triad: Horner syndrome + shoulder pain + atrophy of hand muscles

5) Pericardial involvement → pericardial effusion / tamponade

Metastatic symptoms

Most common sites of metastasis of lung cancer include → lymph nodes, liver, adrenal glands, bone, brain and pleura ^[Ref]

Lymph nodes

• Usually asymptomatic
• Large, bulky nodes may cause airway compromise (leading to cough, dyspnoea, wheeze) or oesophageal compression (dysphagia)

Liver

• Early → nonspecific symptoms (e.g., weakness, weight loss, fatigue)
• Late → hepatomegaly, jaundice
• Abnormal LFTs

Adrenal

• Usually silent; may rarely cause adrenal insufficiency

Bone 

• Localised bone pain, bony tenderness
• Pathological fractures
• Vertebral involvement may result in malignant spinal cord compression
• Features of hypercalcaemia (i.e., confusion, constipation, polyuria)

Brain 

• Symptoms depend on location / size of the metastasis
• May include:
  • Raised ICP features (postural headache, N&V)
  • Focal neurological deficits
  • Altered mental status

Pleura

• (Malignant) pleural effusion
  • Progressive dyspnoea & pleuritic chest pain
  • O/E: ipsilateral reduced breath sounds and dullness (stony) to percussion

Paraneoplastic Syndromes

Category	Syndrome	NSCLC	SCLC	Mechanism	Key Features
Shared paraneoplastic syndromes	Dermatomyositis	✓	✓	Autoimmune	Proximal muscle weakness, rash (e.g., heliotrope)
	Acanthosis nigricans	✓	✓	Secretion of TGF-α	Hyperpigmented plaques (neck, axillae)
	Migratory thrombophlebitis (Trousseau’s syndrome) / Thrombophilia	✓ (esp adenocarcinoma)	✓	Secretion of procoagulant factors	VTE / recurrent superficial, migratory venous thromboses
Endocrine	Hypercalcaemia of malignancy	✓ (esp squamous)		Secretion of PTHrP	‘Stones (nephrolithiasis), bones (bone pain, arthralgias), thrones (polyuria, constipation), groans (abdominal pain, nausea / vomiting), and psychiatric overtones (anxiety, depression, fatigue)’
	Cushing’s syndrome		✓	Secretion of ACTH	Hypertension, central obesity, proximal weakness, abdominal striae…
	SIADH		✓	Ectopic ADH secretion	Hyponatraemia → confusion, seizures, headache…
Other	Hypertrophic osteoarthropathy (HPOA)	✓ (esp adenocarcinoma)		Growth-factor mediated periostitis	Digital clubbing, painful swollen joints, periostitis on X-ray
	Lambert-Eaton myasthenic syndrome (LEMS)		✓	Anti-VGCC antibodies (↓ ACh release)	Proximal weakness improving with activity, autonomic dysfunction, hyporeflexia
	Paraneoplastic cerebellar degeneration		✓	Association with anti-Hu / anti-Yo antibodies	Gait / limb ataxia, dysarthria, nystagmus

Prognosis

Prognosis is highly dependent on histological subtype, stage at diagnosis, and completeness of treatment.

NSCLC (especially adenocarcinoma) generally has more favourable outcomes than SCLC, however, all subtypes tend to have a low survival rate if advanced. ^{[Ref 1] [Ref 2] [Ref 3]}
​​

Subtype	5-Year survival rate (%)	Notes
Adenocarcinoma	20-25	Best prognosis of NSCLC’s
Squamous cell carcinoma	15-20	Slightly worse than adenocarcinoma
Large cell carcinoma	9-15	Poorest among NSCL; often advanced at diagnosis
Small-cell lung cancer	6-7 (advanced/extensive) 20-30 (early/limited)	Poorest overall; most present with advanced disease at diagnosis

Overview

Tumor type	(%) of all lung cancers	Smoking link	Pathological features	Lung location	Key paraneoplastic syndromes
Adenocarcinoma (NSCLC)	45-57 %	Weakest	Glandular differentiation with mucin production	Peripheral	Hypertrophic  osteoarthropathy Migratory thrombophlebitis Gynaecomastia
Squamous cell carcinoma (NSCLC)	12-29 %	Strong	Keratinisation (keratin pearls) and/or intercellular bridges	Central	Paraneoplastic hypercalcaemia
Large cell carcinoma (NSCLC)	6-8 %	Intermediate	Diagnosis of exclusion; undifferentiated NSCLC, with large tumour cells, lacking features of the other subtypes	Peripheral	Gynaecomastia
Small cell carcinoma (SCLC)	9-14 %	Strong	Neuroendocrine Kulchitsky cells	Central	SIADH ACTH (ectopic) dependent Cushing’s syndrome Lambert-Eaton myasthenic syndrome

Screening Guidelines

Screening Pathway

All 55-74 y/o adults who are current or former smokers (with significant smoking history) are invited for a lung health check:

• High risk → offer low-dose CT chest
  • If no significant findings  → repeat scan every 2 years until no longer eligible by age or other exclusion criteria
  • If suspected lung cancer or abnormal findings → refer to secondary care

 

• Low risk → no action needed + recalled to repeat lung health check every 2 years

Disclaimer

Content Creation

The content of this article is a simplified version of the comprehensive NICE guideline. It has been carefully condensed and tailored to highlight the most essential, exam-important knowledge and concepts.

Diagnosis Guidelines

Diagnostic Tests

Imaging (to evaluate suspected lung cancer):

• 1st line: chest X-ray
• 2nd line (all patients with suspicious X-ray findings): CT thorax with contrast (including liver, adrenals and lower neck)

Biopsy (to confirm diagnosis):

• Peripheral lung lesion: image-guided biopsy (i.e., CT-guided transthoracic needle biopsy)
• Central lung lesion: flexible bronchoscopy
  • If unable to tolerate bronchoscopy: sputum cytology

Staging Tests

Mediastinal staging:

• 1st line: bronchoscopy with EBUS-TBNA
• 2nd line (if EBUS-TBNA is -ve but suspicion is high): surgical staging (VATS most common)

Whole body staging:

• PET-CT – to be offered before curative treatment in all patients

Management Guidelines

Definitive Management

ALL patients should be advised to stop smoking as soon as the diagnosis of lung cancer is suspected (see this article for information on smoking cessation).

Non-Small Cell Lung Cancer (NSCLC)

Early-Stage (I-III) NSCLC

1st line: offer curative surgery (open / thoracoscopic lobectomy) +/- extensive surgery (e.g. bronchoangioplastic surgery, bilobectomy, pneumonectomy) to obtain clear margins

• Consider surgery + chemoradiotherapy in stage IIIA-N2

If surgery is inappropriate (e.g. contraindicated or declined):

• Stage I-IIA: stereotactic ablative radiotherapy
• Stage II-III: chemoradiotherapy

Advanced NSCLC (Stage IV or Metastatic)

Offer systemic anti-cancer therapy, guided by tumour properties, options include:

• Platinum-based chemotherapy
• PD-L1 inhibitor (e.g. pembrolizumab)
• Tyrosine kinase inhibitors for specific mutations
  • EGFR
  • ALK
  • ROS1
  • BRAF V600 E
  • KRAS G12C

Small Cell Lung Cancer (SCLC)

Curative surgery should only be considered in early-stage SCLC (T1-2a, N0, M0)

Otherwise, cisplatin-based chemoradiotherapy is the standard approach

Palliative Management

Palliative radiotherapy should be offered to those who are not suitable for curative treatment.

Management of Specific Complications

Complication	Management
Pleural effusion	Acute symptomatic relief: pleural aspiration / drainage Long-term: talc pleurodesis
Cough	Consider opioids (codeine or morphine)
Superior vena cava obstruction	Dexamethasone and endovascular stenting are commonly used initially to relieve symptoms Definitive: chemotherapy and radiotherapy to shrink the tumour

Management of Metastasis

Metastases location	Management
Brain	Dexamethasone
Bone	Radiotherapy if standard analgesics are inadequate

References