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Lung Cancer

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Lung cancer\: arises from malignant epithelial cells in the lungs; most common cancer worldwide and leading cause of
cancer death.
Classi
cell carcinoma.
Lung cancer types\:
Adenocarcinoma\: located peripherally (in smaller airways)
More common in non-smokers, metastasises early, responds well to immunotherapy
Squamous cell carcinoma\: located centrally (in the bronchi)
More common in smokers, secrete PTHrP (hypercalcaemia), metastasises late via lymph nodes
Large cell carcinoma\: located peripherally and centrally
More common in smokers, metastasises early
Small cell carcinoma\: located centrally
More common in older smokers, metastasises early, secretes ACTH (Cushing's syndrome) and ADH (SIADH), associated
with Lambert-Eaton syndrome
Risk factors\: tobacco smoking (80% of cases), air pollution, family history, male sex, radon gas.
Symptoms\: unexplained cough (≥3 weeks), unintended weight loss, new-onset dyspnoea, pleuritic chest pain, bone pain,
fatigue.
Clinical examination\: cachexia,
auscultation.
Investigations\: chest X-ray (
Management\:
Non-small cell lung cancer\:
Stage I-III\: surgery, pre/post-operative chemo-radiotherapy, SABR if unsuitable for surgery.
Stage IV\: targeted therapy, immunotherapy, chemotherapy, palliative care.
Small cell lung cancer\: chemotherapy, radiotherapy, prophylactic cranial irradiation.
Complications\:
Disease-related\: Horner’s syndrome, superior vena cava obstruction, paraneoplastic syndromes.
Treatment-related\: chemotherapy (alopecia, neutropaenia), radiotherapy (mucositis, pneumonitis).
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A comprehensive topic overview

Introduction

Lung cancers arise from malignant epithelial cells in the lungs. Globally, lung cancer is the most common cancer (11.6% of
new cancer diagnoses) and is the leading cause of cancer death (18.4% of total cancer deaths). 1
In the UK, the incidence of
lung cancer is 43,000. On average, a full-time general practitioner diagnoses approximately one case of lung cancer every
year. 2 3
Despite its prevalence, lung cancer has a poor prognosis, with a 5-year survival rate of 17%.
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Aetiology

Classi

Lung cancers are split into two categories\: non-small cell carcinoma (85%) and
small cell carcinoma (15%). This distinction is based on the size of the malignant cells seen on microscopy. Non-small cell
carcinomas are further classi
cell carcinoma (10%). 4
Table 1 illustrates important features of each lung cancer subtype. Table 1 Important features of lung
cancer subtypes
5
Lung cancer type Pathology Clinical features
Adenocarcinoma
Located peripherally (in the
smaller airways) Histology\:
glandular di
More common in non-smok
and Asian females Metastas
early Responds well to
immunotherapy
Non-small cell carcinoma
Squamous cell carcinoma
Located centrally (in the
bronchi) Histology\: squamous
di
More common in smokers
Secrete PTHrP, causing
hypercalcaemia Metastasise
late (via lymph nodes)
Large cell carcinoma
Located peripherally and
centrally Histology\: large and
poorly-di
More common in smokers
Metastasise early
Small cell carcinoma
Located centrally Histology\:
poorly-di
More common in older smo
Metastasise early Secrete AC
(Cushing’s syndrome) and AD
(SIADH) Associated with
Lambert-Eaton syndrome

Risk factors

The main risk factor is tobacco smoking, which is associated with 80% of lung cancer cases. 6
Other important risk factors
include\:
Air pollution (indoor and outdoor)
Family history of cancer, especially lung cancer
Male sex
Radon gas (typically a
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Clinical features

History

Typical symptoms of lung cancer include\:
Unexplained cough for at least 3 weeks (with or without haemoptysis)
Unintended weight loss (>5% in 6 months)
New-onset dyspnoea
Pleuritic chest pain (due to the tumour invading the pleura or the chest wall)
8
Bone pain (due to metastases - commonly the spine, pelvis and long bones)
9
Fatigue (due to anaemia of chronic disease)
Note that up to 20% of patients present with non-respiratory symptoms (such as fatigue). 10
Other important areas to cover
in the history include\:
Family history\: lung cancer in a
7
Smoking history\: quantify in pack-years (1 pack-year = smoking 20 cigarettes a day for a year). Also ask about passive
smoking (second-hand smoking), as this can cause lung cancer.
11
Occupation\: may be exposed to indoor air pollution or radon gas (e.g. miners).

Clinical examination

A full respiratory examination should be performed in suspected cases of lung cancer. See
the Geeky Medics guide here for further information. Typical clinical
Cachexia\: cancer can cause increased resting energy expenditure and lipolysis.
12
Finger clubbing (Figure 1)\: the exact mechanism is unknown, but it may be due to increased secretion of growth factors,
leading to the growth of the extracellular matrix in the nails.
13
Dullness to percussion\: due to the tumour (solids are less resonant than gases).
Cervical lymphadenopathy (Figure 2)\: due to metastasis to the lymphatic system.
Wheeze on auscultation\: due to the tumour obstructing an airway.
Figure 1. Finger clubbing 14

When to refer urgently

Patients presenting with “red-
. This
means that the patient must be seen by a hospital specialist within 2 weeks of the hospital receiving the referral form. The
patient should also have a chest X-ray within 2 weeks. The NICE criteria for a 2-week wait referral for lung cancer are\:
Chest X-ray
Over 40 years old and unexplained haemoptysis
16
Other patients may just need an urgent chest x-ray (within 2 weeks) before a decision to refer on a 2-week wait is made.
These patients must be over 40 years old, and have two of the following unexplained symptoms (one if they have ever
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smoked)\:
Cough
Weight loss
Appetite loss
Dyspnoea
Chest pain
Fatigue
17

Di

Unexplained cough and weight loss have important di
the features which di
Di
Tuberculosis
Drenching night sweats Positive sputum culture and
microscopy Chest X-ray\: cavitating lesion/hilar
lymphadenopathy
Metastasis to the lungs from other sites
Symptoms relevant to the primary tumour (e.g. haematuria
due to renal cell carcinoma) CT head-abdomen-pelvis\:
shows primary tumour FDG-PET\: increased uptake at the
primary tumour site
Sarcoidosis
Enlarged parotids Skin signs\: erythema nodosum and
lupus pernio Tissue biopsy\: non-caseating granulomas
Granulomatosis with polyangiitis (Wegener’s disease)
Saddle-nose deformity Positive cANCA Urinalysis\:
haematuria, proteinuria, red cell casts
Non-Hodgkin’s lymphoma
Drenching night sweats Hepatosplenomegaly Positive
lymph node biopsy (anti-CD20 stain)

Investigations

Bedside investigations

Pulse oximetry\: aim for 94-98% (88-92% if the patient also has COPD – see the Geeky Medics guide on COPD).
ECG\: always performed pre-operatively.

Laboratory investigations

FBC\: may show anaemia.
LFTs\: raised ALP and GGT may indicate hepatic metastases, raised ALP may indicate bone metastases.
U&E\: in order to know the patient's baseline before treatment. Hyponatraemia may be due to syndrome of inappropriate
antidiuretic hormone secretion (SIADH), which is more common in small cell carcinoma.
Serum calcium\: elevated with the secretion of PTH-related protein (PTHrP), which is more common in squamous cell
carcinoma.

Imaging

Chest X-ray (
e
CT chest-abdomen-pelvis (
despite a negative chest X-ray. CT of abdomen and pelvis assesses for metastases.
Bronchoscopy and biopsy (
visualise the tumour. A biopsy of the tumour is taken, and then a pathologist con
the lung cancer subtype (e.g. adenocarcinoma) and the presence of targetable mutations (e.g. EGFR mutation – see the
management section). A biopsy is essential in order to make the diagnosis of lung cancer.
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Positron emission tomography CT (PET-CT)\: enables staging of lung cancer (see table 3).
Figure 3. Chest x-ray showing lung cancer in the right upper zone 18

Staging of lung cancer

This is a summarised version of the staging criteria; any more detail is beyond the scope of
undergraduate learning. Note that the TNM staging classi
system which is used to guide management decisions. Table 3 Lung cancer staging.
21
Stage Description
I One small tumour (\<4cm) – localised to one lung
II Larger tumour (>4cm) – may have spread to nearby lymph nodes
III
Tumour that has spread to contralateral lymph nodes, or grown into
nearby structures (e.g. trachea)
IV
Tumour that has spread to lymph nodes outside the chest, or other
organs (e.g. liver)

Management

Non-small cell lung cancer

Stage I – III
Surgery\: options include lobectomy/pneumonectomy in patients with intact lung function, or wedge resection in
patients with reduced lung function (e.g. elderly, underlying respiratory conditions).
Pre-operative chemotherapy
Post-operative chemotherapy and radiotherapy\: may not be needed in some cases of stage I lung cancer.
If unsuitable for surgery (e.g. too frail), patients may be o
conventional radiotherapy, SABR involves directing a more intense and focused beam of radiation at the tumour. This
reduces the number of radiotherapy sessions needed and minimises damage to surrounding tissue.
22
Stage IV
Targeted therapy\: these drugs target mutations which drive the pathogenesis of lung cancer (Table 3). Medical students
should be aware that these targeted therapies exist and are used for stage IV lung cancer, but do not need to know
much more detail than this.
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Immunotherapy\: these drugs target immune checkpoints, which prevent the patient’s immune cells from killing tumour
cells. For example, the immune checkpoint PD-L1 is targeted by pembrolizumab. Immunotherapy is an emerging
cancer management.
Chemotherapy\: especially important for patients who do not have any mutations which can be targeted by targeted
therapies.
Palliative care\: includes palliative radiotherapy, for metastases and symptom control.
Table 3 Examples of targeted therapy for non-small cell lung cancer
Mutation Drug
EGFR
Ge
Osimertinib
ALK Alectinib
ROS1 Crizotinib

Small cell lung cancer

Chemotherapy and radiotherapy
Surgery\: rare in small cell lung cancer, as most patients present with advanced disease.
Prophylactic cranial irradiation\: since small cell lung cancer is associated with a high risk of brain metastases,
radiotherapy is directed at the brain to prevent brain metastases.

Complications

Horner’s syndrome (
ptosis, miosis, anhidrosis (reduced sweating) and enophthalmos (posterior displacement of the eyeball into the orbit).
This is a common exam question!
Superior vena cava obstruction (
from the head and neck, leading to facial swelling and distended neck/chest veins.
Paraneoplastic syndromes\: such as SIADH and Lambert-Eaton syndrome.

Due to chemotherapy\: alopecia, neutropaenia, bone marrow toxicity.
Due to radiotherapy\: mucositis, pneumonitis, oesophagitis.
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Figure 6. Left-sided Horner’s syndrome. Ptosis, miosis and mild enophthalmos are visible 23

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Reviewer

Dr Neeraj Shah
Respiratory Medicine Registrar

Asthma
Bronchiectasis
Chronic Obstructive Pulmonary Disease (COPD)
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