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Lung cancer
Lung cancer

Lung cancer

Lung cancer is the 3rd most common cancer globally (after breast and prostate) but is the cancer with the greatest mortality rates.

🔢 Classification

There are 2 main types of lung cancers:

  1. Non-small cell lung cancer (NSCLC) - 80%
  2. Small cell lung cancer (SCLC) - 20%
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Non-small cell lung cancer (NSCLC)

It accounts for 80% of all lung cancers. It involves the cells that are histologically “big” cells. Depending on the type of cell involved, we can divide it further into:

  • Adenocarcinoma (40%)

      • Involve the glandular/secretory cells of the lung, such as those that are mucous secreting (goblet cells). They are the most common type of lung cancer in both smokers and non-smokers (62% of cases are non-smokers). These tend to be peripherally located within the lungs (almost all other lung cancers are usually central).

      Common sites of metastasis are bones and brain.

      It is associated with:

    1. Hypertrophic pulmonary osteoarthropathy (HPOA) - also called Bamberger–Marie syndrome. It is characterised by inflammation of wrist and anklejoints.
    2. Pleural effusions
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  • Squamous cell carcinoma (25%)

      • SCCs of the lung line the lower respiratory tracts and are located more centrally, within the airways. They make up 18% of non-smoker lung cancer cases.

      They often present with chest infections due to obstructive lesions causing infections.

      It is associated with:

    1. Hypercalcaemia - due to the secretion of parathyroid hormone-related protein.
    2. Finger clubbing
    3. HPOA
    4. Cavitations lesions - these are necrotic lesions that essentially leave holes in the lung.
  • Large cell carcinoma (10%)

    • Large cell carcinomas are undifferentiated anaplastic tumours without the histological features of typical SCCs or adenocarcinomas. They may be central or peripheral. Its prognosis is poor.

    It may secrete ß-HCG hormone in the blood and so a raise in ß-HCG may be seen in blood results.

Other less prominent NSCLCs include:

  1. Alveolar cell carcinoma - seen in non-smokers and characterised by large amounts of sputum production.
  2. Bronchial carcinoid tumour (bronchial adenoma) - a neuroendocrine pulmonary tumour.

These make up <10% of lung cancer cases.

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Small cell lung cancer (SCLC)

These account for ~20% of all lung cancers. They are very aggressive malignancies involving histologically small and densely packed cells. It was previously referred to as oat cell carcinoma.

About 2/3rds of patients present initially with distant metastases already.

It arises form neuroendocrine cells of the lung known Kulchitsky cells. They are also known as amine precursor uptake and decarboxylase cells (APUD cells).

These cells uptake amine precursors and have a high content of the enzyme decarboxylase. This tumour results in secretion of polypeptides and neuroendocrine hormones such as ACTH which can be responsible for paraneoplastic syndromes (discussed later).

They tend to be more central with mediastinal involvement.

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Mesothelioma is also a cancer that affects the lung (more specifically the pleura). This is covered in the CCC on asbestos-related lung disease.

⚠️ Risk factors

⭐️ Smoking tobacco is the most significant risk factor for lung cancer. Approximately 90%+ of the lung cancers in Europe are directly attributable to smoking.

Other risk factors include:

  • Passive smoking/environmental tobacco exposure
  • Occupational lung diseases - such as asbestosis or silicosis
  • Radon gas exposure - radon is a product of uranium decay. It may be able to percolate into homes where it can further decompose into polonium which causes DNA damage and may increase risk of malignancy.
  • Family history

😷 Presentation

🚩
Red flag symptoms:
  1. Weight loss
  2. Haemoptysis
  3. Persistent cough
  4. Persistent dyspnoea
  • Chest pain
  • Nausea and vomiting
  • Anorexia
  • Recurrent chest infections
  • Hoarse voice - in a pancoast tumour. As this may compress the recurrent laryngeal nerve.
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Signs of lung cancer:
  • Clubbing of fingers
  • Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
  • Cachexia
  • Monophonic wheezing
  • Paraneoplastic syndromes
  • Dull percussion - may be due to a pleural effusion that occurs due to inflammatory reactions that occur with cancers.
  • Deviated trachea
  • Horner’s syndrome - once again with a pancoast tumour.
    • Ptosis
    • Miosis
    • Anhidrosis
  • Pneumothorax - invasive tumours may breach the pleura leading to a pneumothorax.
  • Atelectasis - total obstruction of the airway can lead to collapsing of the lung.
  • Superior vena cava syndrome/obstruction - compression of the tumour on the SVC may lead to facial swelling, dyspnoea and distended veins in the neck/upper thorax.
    • Pemberton’s sign - this is due to compression of the thoracic inlet with positional changes. It is usually due to a thyroid goitre but may also occur due to lung cancer, thymoma or even aortic aneurysms. It presents with facial congestion (redness) and cyanosis.
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Let’s now take a look at paraneoplastic syndromes and what these entail…

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Paraneoplastic syndromes:

These are a group of uncommon disorders that may develop alongside the cancer. They may affect the endocrine, dermatological, haematological and rheumatological systems.

  • SCLC paraneoplastic syndromes
  1. Cushing’s syndrome - ectopic ACTH production by the SCLC may lead to an excess of cortisol. ACTH can also lead to aldosterone secretion which increases potassium excretion through the Na+/K+-ATPase → hypokalaemic alkalosis.
  1. Syndrome of inappropriate ADH secretion (SIADH) - ectopic ADH secretion leads to excessive water retention → hyponatraemia.
  1. Lambert Eaton Myasthenic syndrome - antibodies produced against the SCLC also act upon VGCa2+ channels on presynaptic terminals of motor neurons at the NMJ. Damage of these prevent synaptic vesicle release, thus leading to:
    1. Motor weakness - primarily in proximal muscles
    2. Diplopia - due to weakness of intraocular muscles
    3. Ptosis - weakness of levator palpebrae muscles
    4. Dysphagia and slurred speech - due to weakness of pharyngeal muscles
    5. Dry mouth, blurred vision, impotence, constipation - all relating to autonomic dysfunction.
    6. Reduced tendon reflexes - their reflexes may become normal after strong muscle contraction, however. For example, after contracting their quadriceps strongly, the knee jerk reflex may show an improvement in the response. This is known as post-tetanic potentiation or post-exercise facilitation.
  1. Limbic encephalitis - antibody production against brain tissue, especially within the limbic system. This leads to an inflammatory response that may cause issues such as short term amnesia, hallucinations, confusions and seizures. Anti-Hu antibodies are most commonly implicated.
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Post-tetanic potentiation
Post-tetanic potentiation
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  • SCC and other NSCLS paraneoplastic syndromes
  1. Hypercalcaemia - due to excessive parathyroid hormone-related protein secretion.
  2. Hypertrophic pulmonary osteoarthropathy (HPOA) - joint stiffness, severe pain in wrists and ankles and even gynaecomastia.
    1. It may appear on X-ray as a multilayered periosteal reaction at the ends of long bones. This presents with an onion skin appearance. It is also associated with clubbing.
  3. Hyperthyroidism - due to ectopic TSH secretion.

🔍 Investigations

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Imaging
  • 🥇 CXR

This is the 1st line investigation in all patients with suspected lung cancer.

We may see:

  1. Nodules
  2. Lung collapse
  3. Pleural effusion
  1. Consolidation
  2. Bony metastases
  3. Hilar enlargement
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  • 🏆 Contrast enhanced CT scan - used to confirm the diagnosis and stage the disease (using the TNM classification). The scan should include the adrenals and liver to look for metastases.
  • 👀 PET scan - is used to establish one’s eligibility for curative treatment. It is typically done in NSCLC as it may be curative.
    • 18-flurodeoxygenase is the radioactive substance that binds to glucose and is taken up preferentially by neoplastic tissue as it is more metabolically active.
    • PET scans also improve diagnostic sensitivity for local and distant metastases.
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Other investigations include:

  • Bronchoscopy with biopsy - to obtain histological sample.
  • Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) - allow biopsy of lymph nodes, paratracheal and bronchial lung lesions for histology.
  • Mediastinoscopy - may also be used to obtain biopsy.
  • Sputum cytology
  • CVS review and lung function tests - to assess suitability for treatment.
  • Bloods - a raised platelet count may be seen.

📝 Referral criteria

In 2021, NICE updated their referral criteria for suspected lung cancers:

NICE recommends offering a CXR on suspected cancers, within 2 weeks to patients >40 years old with any of the following:

  • Finger clubbing
  • Lymphadenopathy
  • Recurrent or persistent chest infections
  • Thrombocytosis
  • Chest signs of lung cancer

NICE recommend considering a CXR in patients >40 years old with:

  • 2+ unexplained symptoms in patients that have never smoked.
  • 1+ unexplaned symptoms in patients that have ever smoked.

Unexplaineded symptoms include:

  1. Cough
  2. Dyspnoea
  3. Fatigue
  1. Chest pain
  2. Weight loss
  3. Loss of appetite

🧰 Management

🫁
SCLC management

This is based off of the NICE 2011 guidance.

SCLS is more aggressive. Most patients present with an already disseminated disease and as a result palliative care is often the primary management.

Limited-stage disease

  1. Cisplatin-based combination chemotherapy- 4-6 cycles with other chemotherapy options and radiotherapy concurrently.
  2. Surgery - considered in patients with T1-2a/N0/M0.

Extensive-stage disease

  1. Platinum-based combination chemotherapy

Patients who have relapsed after treatment need referral to thoracic oncologist.

💡
NSCLC management

This is based off of the NICE 2019 guidance.

  1. Lobectomy - is the option for patients with curative intent.
    1. More extensive surgeries such as bronchoangioplastic surgery or bilobectomy or pneumonectomy are only done when necessary to obtain clear margins.

If surgery is declined or contraindicated (contraindications mentioned below):

  • Stage 1-2 - offer radical radiotherapy with stereotactic ablative radiotherapy or sublobar resection (wedge resection or segmentectomy)
  • Stage 3-4 - offer combination chemoradiotherapy with a cisplatin-based regiment for adjuvant chemotherapy.

The contraindications to surgery include:

  1. Generally unfit for surgery - for example if too frail.
  2. Stage IIIb or IV - i.e. metastases present
  3. FEV1 <1.5L
  4. Malignant pleural effusion
  1. Tumour near the hilum
  2. Vocal cord paralysis
  3. SVC obstruction
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Surgical approaches

The 3 main thoracotomy incisions include:

  1. Anterolateral thoracotomy
  2. Axillary thoracotomy
  3. Posterolateral thoracotomy

A chest drain will be left in-situ after surgery to allow air and fluid to exit thus enabling expansion of the lungs. The external end of the drain is placed in water to create a seal that prevents air flowing back through the drain and into the chest. Air will be able to exit the thoracic cavity and will bubble through the water but it will not be able to re-enter. The water will rise and fall during normal respiration due to the changes in pressure.

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