Lung cancer

Notes

Definition & classification

Lung cancer is a common malignant tumour, with 41,000 cases diagnosed in the UK each year. It is the leading cause of death from cancer in the UK

Aetiology

Smoking is by far the most important aetiological factor. Exposure to other environmental agents may also increase the risk of developing lung cancer.

Smoking

Tobacco smoking is thought to be the cause of lung cancer in 80-90% of cases. Differences in gender mean women are somewhat less susceptible.

The effects of smoking remain long after cessation. The relative risk remains around two times that of a non-smoker at 30 years post cessation.

Exposure

Asbestos, a fibrous building material, is perhaps the best-known carcinogen aside from tobacco. Unfortunately, Britain spent years as one of the largest importers of the material. Despite its use being illegal for decades in the UK, cases of asbestos-related disease are still seen as many of its effects appear after a lag.

Though more strongly associated with mesothelioma, asbestos is linked with adenocarcinoma of the lung. Tobacco and asbestos exposure act synergistically increasing the risk of cancer multiple times.

Radon gas, released from naturally occurring uranium, is a recognised cause of lung cancer.

Pathophysiology

Lung cancers are divided by the cell type responsible, two broad categories exist, non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). 

Non-small cell lung cancer

Non-small cell lung cancer account for around 85% of lung cancers.

Changing trends in incidence is a reflection of the timing of countries smoking epidemics.

1. Adenocarcinoma

Adenocarcinoma is now the most common form of lung cancer (around 38%). It is a cancer of the mucus-secreting cells.

Its incidence relative to other forms of lung cancer has shown an increase. It also appears proportionally more in non-smokers than squamous cell carcinoma. Smoking and asbestos exposure are both risk factors.

Adenocarcinoma tends to occur in lung peripheries.

2. Squamous cell

Squamous cell carcinoma is the second most common form of lung cancer (around 20%). Occurring in central parts of lungs, it often presents with pneumonia secondary to an obstructed bronchus.

Smoking is the most common cause. Metastases tend to occur late and histopathology shows keratin.

3. Large cell

These are undifferentiated neoplasms accounting for around 5% of lung cancers. They tend to metastasise early.

Small cell lung cancer

Account for around 15% of lung cancers. Considered separately due its fast doubling time, aggressive nature and early metastasis.

SCLC is a cancer of the APUD cells, a neuroendocrine cell found in the lungs. It occurs almost exclusively in smokers.

It has an extremely poor prognosis, by the time of diagnosis curative therapy is rarely possible. SCLCs are commonly associated with paraneoplastic syndromes.

Clinical features

Lung cancer is frequently asymptomatic. When symptomatic, cough, malaise and weight loss predominate.

It may also present with haemoptysis, features of superior vena cava obstruction (SVCO) or a paraneoplastic syndrome. A higher index of suspicion is necessary for patients with a history of smoking.

Symptoms

  • Fever
  • Malaise
  • Nausea
  • Cough
  • Haemoptysis 
  • Hoarseness
  • Weight loss

Signs

  • Lymphadenopathy 
  • Stridor
  • Wheeze
  • Clubbing
  • Hypertrophic pulmonary osteoarthropathy (HPOA)
  • Signs of pleural effusion (exudative):
    • Dull (‘stony dull') percussion
    • Reduced vocal fremitus
    • Reduced breath sounds

Superior vena cava obstruction

A tumour may cause compression of the superior vena cava. This causes engorgement of vessels in the neck and face, shortness of breath and a ‘fullness’ of the head. 

This represents one of the acute oncological emergencies.

Pancoast tumour

This is a tumour of the superior sulcus of the lung. Their location means local spread may affect:

  • Brachial plexus
  • Cervical sympathetic trunk and the stellate ganglion
  • Subclavian vein

Pancoast tumours are known to cause:

  • Horner’s syndrome
  • Pain in the shoulder that radiates into the arm and hand
  • Atrophy of muscles of the upper limb
  • Oedema of the upper limb

Metastasis

Metastasis may cause a variety of clinical features:

  • Bone: bone pain, raised ALP
  • Brain: focal and non-focal neurology
  • Liver: abnormal LFTs
  • Adrenal glands: though a common site of metastasis, normally asymptomatic

Paraneoplastic syndromes

Paraneoplastic syndromes refer to remote effects of tumours unrelated to mass effect, invasion or metastasis.

Hypercalcaemia

Hypercalcaemia may occur in lung cancers due to:

  • Bony metastasis
  • Tumour secretion of:
    • Parathyroid hormone-related protein (PTHrP) 
    • Calcitriol 

Clinical manifestations of hypercalcaemia are often remembered by “stones, bones, groans, thrones, and psychiatric moans”. This refers to renal calculi, bone pain, abdominal pain, polyuria and signs of altered mental status.

Hypercalcaemia is common in lung carcinoma, seen in approximately 50% of patients with squamous cell carcinoma, 20% of adenocarcinoma and 15% of small cell carcinoma.

SIADH

The syndrome of inappropriate anti-diuretic hormone is seen in around 10% of patients with SCLC. Symptoms are those of hyponatraemia and in extreme cases, cerebral oedema may occur.

See notes titled ‘SIADH’ for more details.

Cushing’s syndrome

Cushing’s syndrome is caused by exposure to high levels of glucocorticoids. In rare cases, lung cancers produce ectopic ACTH driving an increase in glucocorticoids.

Lambert-Eaton syndrome

This syndrome is caused by antibodies to voltage-gated calcium channels. It is seen in 1-3% of SCLC. It is characterised by both proximal and ocular muscle weakness.

Hypertrophic osteoarthropathy 

This syndrome is characterised by clubbing and periostitis. It features a symmetrical, painful arthropathy affecting the distal joints.

Referral guidance

Patients with risk factors and clinical features of lung cancer require prompt referral for further investigations.

Urgent:

  • SVCO
  • Stridor

Two week wait:

  • Suggestive CXR findings
  • Unexplained haemoptysis and aged over 40

Consider urgent CXR in those aged over 40 with:

  • Persistent or recurrent chest infection
  • Clubbing
  • Lymphadenopathy
  • Chest signs indicative of lung cancer
  • Thrombocytosis 

Consider urgent CXR in those aged over 40 with two of the following:

  • Smoking history or asbestos exposure
  • Cough
  • Fatigue
  • Shortness of breath
  • Chest pain
  • Weight loss
  • Appetite loss

Investigations & Diagnosis

Investigations look for evidence of a primary lung cancer, this involves imaging and tissue sampling. It is necessary to identify the cell type, the extent of invasion, nodal involvement and any metastasis.

Bedside

  • Observations
  • Blood pressure
  • Lung function tests

Bloods

  • FBC
  • U&Es
  • LFTs

Imaging

  • CXR
  • CT scan
  • PET-CT
  • Bronchoscopy 

Special tests

Tissue biopsy:

  • Obtained via endoscopy, video-assisted thoracoscopic surgery (VATS), mediastinoscopy.
  • Obtained from the tumour, lymph node or metastasis.

Cytology:

  • From aspirates, washings, pleural fluids.
  • Obtained from the tumour, lymph node or metastasis.

TNM staging

Staging helps guide management as well as providing prognostic information

NSCLC is staged using the tumour node metastasis (TMN) staging system (based upon IASLC 8th Edition Lung Cancer TNM staging guidelines). SCLC may also be staged this way, though the VALSG staging system may be used instead/in conjunction with it.

1. Tumour

T0: no cancer

Tis: carcinoma in situ

T1:

  • 2 - 3 cm

T2

  • 3 - 5 cm or
  • Any size that invades main bronchus, without carina or visceral pleura or
  • Atelectasis or post obstructive pneumonitis extending to hilum.

T3:

  • 5 - 7 cm or
  • Any size that involves chest wall, parietal pleura parietal pericardium or phrenic nerve or
  • Satellite nodule in same lobe.

T4

  • > 7 cm or
  • Any size that invades diaphragm, mediastinum, vertebrae, carina, heart, great vessels, RLN or oesophagus or
  • Ipsilateral tumours in separate lobe.

2. Node

N0:

  • No lymph node involvement.

N1:

  • Ipsilateral peribronchial, hilar and/or intrapulmonary nodes.

N2:

  • Ipsilateral mediastinal and/or subcarinal nodes.

N3:

  • Ipsilateral scalene or supraclavicular nodes.
  • Contralateral mediastinal or hilar nodes.

3. Metastasis

M0: no metastasis

M1a: malignant pleural or pericardial effusion, pleural nodules or contralateral metastatic lung nodules. 

M1b: distant metastasis 

Staging

The above categories may then be grouped into stages:

VALSG staging

SCLC may be staged in a more simple two stage system. It is felt this better reflects the limited opportunities for treatment with curative intent.

Limited disease: tumour not spread beyond hemithorax, regional nodes that may be treated with single radiotherapy field.

Extensive disease: tumour spread beyond hemithorax or extensively through the hemithorax, distant metastasis, malignant effusions or contralateral hilar/supraclavicular involvement.

Management

Management is guided primarily by the cancers cell type, staging and the patients performance status. 

All smokers should be encouraged to stop. Below is a broad look at the treatment options. The reality is that management is complex and based upon multiple factors beyond the scope of this note.

NSCLC

Surgical:

  • Utilised in stage I and II disease, typically in the form of a lobectomy.
  • Lymph node sampling during the operation offers prognostic information.

Chemotherapy:

  • May be used in combination with surgery as:
    • Neo-adjuvant: prior to surgery
    • Adjuvant: following surgery 
  • May be offered in those with more extensive disease in which surgery is not appropriate.
  • Third generation chemotherapeutics and platinum agents often used.

Radiotherapy:

  • Often a palliative treatment, to improve symptoms and survival.
  • Radical (with curative intent) radiotherapy may be used in early disease.

SCLC

Surgical:

  • Only an option in early disease, appropriate in <5% of cases.
  • In T1/2 N0 disease surgery with curative intent may be utilised.

Chemotherapy:

  • Typically utilises platinum-based combination therapy.

Radiotherapy:

  • Mostly used for palliative relief.

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