Small Cell Lung Cancer

Small cell lung cancer
Straight to the point of care
Last updated: Jun 13, 2023

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Classification 4
Case history 8
Diagnosis 9
Approach 9
History and exam 11
Risk factors 13
Investigations 14
Differentials 17
Criteria 28
Screening 28
Management 30
Approach 30
Treatment algorithm overview 32
Treatment algorithm 33
Emerging 43
Primary prevention 43
Secondary prevention 43
Follow up 44
Monitoring 44
Complications 45
Prognosis 47
Guidelines 48
Diagnostic guidelines 48
Treatment guidelines 49
References 51
Disclaimer 60
Small cell lung cancer Overview
Summary
Small cell lung cancer (SCLC) is an aggressive malignancy. Approximately two-thirds of patients have
evidence of distant metastasis at presentation. It primarily develops in older adult smokers.
OVERVIEW
Most common presenting symptoms are cough, chest pain, haemoptysis, dyspnoea, and weight loss.
A suspicious lung mass should be biopsied during bronchoscopy or computed tomography (CT)-guided
transthoracic needle aspiration.
Staging studies should include chest/abdomen CT and brain magnetic resonance imaging (preferred) or
head CT, with mediastinoscopy and/or bone marrow aspirate and biopsy in selected cases. If disease
appears to be confined to the chest, positron emission tomography (PET)-CT can be done to assess for
distant metastases. Bone scan can be done if PET-CT is not available. Accurate staging is very important for
treatment selection.
Localised disease (defined as disease that can be contained within a radiation portal) should be treated with
concurrent chemotherapy and radiotherapy. Radiotherapy should be started as early as possible. Surgery
should be offered to patients with clinical T1N0 or T2N0 disease after mediastinoscopy. Extensive-stage
disease should be treated with chemotherapy and immunotherapy. Palliative radiotherapy may be utilized if
necessary. Prophylactic cranial irradiation should be considered for all patients with limited-stage disease.
Definition
Small cell lung cancer (SCLC), previously referred to as oat cell carcinoma, is a malignant epithelial tumour
arising from cells lining the lower respiratory tract. The tumour cells are small and densely packed, with scant
cytoplasm, finely granular nuclear chromatin, and absence of nucleoli.[1]
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Small cell lung cancer Theory
Epidemiology
In the UK, from 2015 to 2017, there were 35,349 deaths from lung cancer every year, accounting for 21% of
all cancer deaths in the UK in that time period.[6] According to the National Cancer Institute's Surveillance
THEORY
Epidemiology and End Results (SEER) registry, lung cancer represents 12.2% of all new cancer diagnoses
and is the leading cause of cancer mortality in the US.[7] An estimated 238,340 people are expected to
be diagnosed with, and 127,070 are expected to die from, lung cancer in the US in 2023.[7] Age-adjusted
incidence (SEER 2016-2020) is higher in males than in females (56.4 new cases per 100,000 vs. 45.3 cases
per 100,000, respectively); incidence rates in the US are highest in black and non-Hispanic white people and
lowest in Native Americans, Hispanics, and Asian/Pacific Islanders.[7]
The incidence of lung cancer appears to change in parallel with the rate of tobacco use. Lung cancer rates
increased dramatically during the mid-1900s, a few decades following the rapid rise in tobacco use. Declines
in the incidence of lung cancer (approximately 2% decrease per year since the mid-2000s in the US and
6.5% decrease in age-standardised incidence globally between 2010 and 2019) may relate to reductions in
tobacco use.[8] [9] The incidence of lung cancer in men began to decline in the 1980s and in women it began
to decline over 10 years later, in the late 1990s. This difference is attributable to historical gender differences
in rates of cigarette smoking over time.[8] The declining incidence of lung cancer has decreased the overall
mortality rate. Small cell lung cancers account for approximately 15% of all lung cancers and nearly all small
cell lung cancers are attributable to cigarette smoking.[10] [11] [12]
Aetiology
The US Surgeon General declared in 1964 that cigarette smoking causes lung cancer in men and that
increased duration and amount of cigarette use increases that risk.[3] Multiple case-control studies were
cited to support this assertion.[13] [14] [15] Tobacco exposure continues to be the most important cause
of lung cancer and approximately 90% of lung cancer is directly attributable to smoking, including virtually
all cases of SCLC.[11] Tobacco smoke contains multiple carcinogens, including polynuclear aromatic
hydrocarbons, aromatic amines, N-nitrosamines, and other organic and inorganic compounds.[16]
Lung cancer has also been linked to radon gas, a radioactive decay product of uranium. Radon can percolate
into homes from the ground below. Radon itself is not dangerous but radon decays into progeny that emit
alpha-particles, which can damage DNA and induce lung cancer.[17]
Pathophysiology
SCLC comprises approximately 15% of lung cancers and is highly associated with smoking relative to
other subtypes of lung cancer.[11] [12] The relative incidence of SCLC is declining, probably reflecting the
decreasing percentage of smokers in the population.[18] These tumours tend to arise in the central lung
with mediastinal involvement. SCLC is an aggressive malignancy. Approximately two-thirds of patients have
evidence of distant metastasis at presentation (extensive stage), while one third present with limited-stage
disease (confined to the ipsilateral hemithorax).[5]
Classification
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 13, 2023.
The 2021 World Health Organization classification of lung
tumours[2]
Epithelial tumours
THEORY
Papillomas
• Squamous cell papilloma, not otherwise specified (NOS)

• Squamous cell papilloma, inverted
• Glandular papilloma
• Mixed squamous cell and glandular papilloma
Adenomas
• Sclerosing pneumocytoma
• Alveolar adenoma
• Papillary adenoma
• Bronchiolar adenoma/ciliated muconodular papillary tumour
• Mucinous cystadenoma
• Mucous gland adenoma
Precursor glandular lesions
• Atypical adenomatous hyperplasia

• Adenocarcinoma in situ
• Adenocarcinoma in situ, non-mucinous

• Adenocarcinoma in situ, mucinous
Adenocarcinomas
• Minimally invasive adenocarcinoma
• Minimally invasive adenocarcinoma, non-mucinous

• Minimally invasive adenocarcinoma, mucinous
• Invasive non-mucinous adenocarcinoma
• Lepidic adenocarcinoma
• Acinar adenocarcinoma
• Papillary adenocarcinoma
• Micropapillary adenocarcinoma
• Solid adenocarcinoma
• Invasive mucinous adenocarcinoma
• Mixed invasive mucinous and non-mucinous adenocarcinoma

• Colloid adenocarcinoma
• Fetal adenocarcinoma
• Adenocarcinoma, enteric type
• Adenocarcinoma, NOS
5
Squamous precursor lesions
• Squamous cell carcinoma in situ

• Mild squamous dysplasia
THEORY
• Moderate squamous dysplasia

• Severe squamous dysplasia
Squamous cell carcinomas
• Squamous cell carcinoma, NOS
• Squamous cell carcinoma, keratinising

• Squamous cell carcinoma, non-keratinising
• Basaloid squamous cell carcinoma
• Lymphoepithelial carcinoma
Large cell carcinomas
• Large cell carcinoma

Adenosquamous carcinomas
• Adenosquamous carcinoma
Sarcomatoid carcinomas
• Pleomorphic carcinoma
• Giant cell carcinoma

• Spindle cell carcinoma
• Pulmonary blastoma
• Carcinosarcoma
Other epithelial tumours
• NUT carcinoma
• Thoracic SMARCA4-deficient undifferentiated tumour
Salivary gland-type tumours
• Pleomorphic adenoma
• Adenoid cystic carcinoma
• Epithelial-myoepithelial carcinoma
• Mucoepidermoid carcinoma
• Hyalinising clear cell carcinoma
• Myoepithelioma
• Myoepithelial carcinoma
Lung neuroendocrine neoplasms
Precursor lesion
• Diffuse idiopathic neuroendocrine cell hyperplasia

Neuroendocrine tumours
• Carcinoid tumour, NOS/neuroendocrine tumour, NOS
THEORY
• Typical carcinoid/neuroendocrine tumour, grade 1
• Atypical carcinoid/neuroendocrine tumour, grade 2
Neuroendocrine carcinomas
• Small cell carcinoma
• Combined small cell carcinoma

• Large cell neuroendocrine carcinoma
• Combined large cell neuroendocrine carcinoma
Tumours of ectopic tissues
• Melanoma
• Meningioma
Mesenchymal tumours specific to the lung
• Pulmonary hamartoma
• Chondroma
• Diffuse lymphangiomatosis
• Pleuropulmonary blastoma
• Intimal sarcoma
• Congenital peribronchial myofibroblastic tumour
• Pulmonary myxoid sarcoma with EWSR1-CREB1 fusion
PEComatous tumours
• Lymphangioleiomyomatosis
• PEComa, benign
• PEComa, malignant
Haematolymphoid tumours
• MALT lymphoma
• Diffuse large B-cell lymphoma, NOS
• Lymphomatoid granulomatosis, NOS
• Lymphomatoid granulomatosis, grade 1

• Intravascular large B-cell lymphoma
• Langerhans cell histiocytosis
• Erdheim–Chester disease
7
Case history
Case history #1
THEORY
A 65-year-old man presents with a 2-month history of a dry persistent cough and 4.5 kg unintentional
weight loss. He reports no history of fevers, dyspnoea, sore throat, rhinorrhoea, chest pain, or
haemoptysis. Past medical history is significant for chronic obstructive pulmonary disease and
hypertension. Family history is non-contributory. He smoked 1 pack of cigarettes daily for 40 years but
quit 5 years ago. No adenopathy was palpable on examination and breath sounds were diminished
globally without focal wheezes or rales.
Other presentations
Lung cancer can present without symptoms. This is due to the large functional reserve of the lungs and
lack of pain fibres within the lung parenchyma. Consequently, lung cancer can present as an incidental
mass on chest x-ray or computed tomography. Eventually, patients develop symptoms from local tumour
growth within the lung, including cough, dyspnoea, chest pain, and/or haemoptysis.[3] [4] Haemoptysis
typically consists of blood-tinged sputum. Massive haemoptysis is rare. Invasion of the pleura or chest
wall can cause chest pain. Obstruction of major airways can cause dyspnoea, wheezing, or post-
obstructive pneumonia. A pneumonia that does not rapidly clear with antibiotics is cause for concern for
lung cancer, especially in patients with a tobacco history.
Lung cancer often spreads to mediastinal lymph nodes. Symptoms from mediastinal adenopathy are
relatively rare. However, bulky adenopathy can cause hoarseness (impingement of the recurrent laryngeal
nerve), paralysis of the diaphragm (impingement of the phrenic nerve), difficulty swallowing (extrinsic
compression of the oesophagus), or superior vena cava syndrome, typically characterised by upper
extremity and facial oedema, orthopnoea, cough, and venous distension of the neck and chest wall.[5]
SCLC is associated with paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome,

peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and Cushing's
syndrome.[5]
Finger clubbing and hypertrophic osteoarthropathy are less common in SCLC compared with non-small
cell lung cancer.[4]
Small cell lung cancer Diagnosis
Approach
Persistent cough associated with haemoptysis or weight loss in a smoker older than 50 years of age are key
features that should alert the clinician to the possibility of lung cancer. However, lung cancer can present
without symptoms as an incidental mass on chest x-ray or computed tomography (CT).
History
Symptoms of a primary tumour include cough, haemoptysis, chest pain, and/or dyspnoea. Some patients
may present with hoarseness, secondary to recurrent laryngeal nerve paralysis. Patients may also
present with non-specific symptoms, such as weight loss or fatigue.
Smoking history, nutritional status, and performance status (an objective assessment of the patient's
ability to perform activities of daily living) should be specifically addressed.
Many patients have distant metastasis at the time of presentation. The most frequent sites of distant
metastasis are the lungs, liver, brain, bone, and adrenal glands. Symptoms depend on the sites and
extent of involvement. Pain or fractures can develop as a result of bone metastasis. Lung cancer is
the most common cause of brain metastasis.[29] Common symptoms of brain metastases include
confusion, personality change, seizures, weakness, focal neurological deficits, nausea and vomiting, and
headaches.
Physical examination
The general appearance of the patient is important. The patient may appear unwell, short of breath, and
have evidence of recent weight loss. The neck and supraclavicular fossae should be carefully examined
for adenopathy. Finger clubbing and hypertrophic osteoarthropathy may be present but are less common
in SCLC compared with non-small cell lung cancer.[4]
Although the pulmonary examination is normal in some patients with early lung cancer, many present with
one or more findings during auscultation. The following signs are common:
DIAGNOSIS
• Wheezing from underlying COPD or bronchial obstruction
• Rales due to post-obstructive pneumonia or atelectasis
• Diminished breath sounds from bronchial obstruction, pleural effusion, and/or COPD.
Pleural effusions can be assessed with percussion of the lung fields, showing a characteristic dullness.
Facial and upper extremity swelling, distended neck veins, and dilated collateral vessels on the chest or
abdominal wall may indicate compression of the superior vena cava.
Paraneoplastic manifestations of SCLC that may be clinically apparent include Cushing's syndrome from
ectopic adrenocorticotrophic hormone secretion and neurological manifestations of myopathy and sensory
neuropathy.
Investigations
A chest x-ray and CT of the chest and upper abdomen are standard and help define the primary tumour
and evaluate for regional spread.
• A standard posteroanterior and lateral chest x-ray is an inexpensive and simple initial step to
evaluate cough, chest pain, and/or haemoptysis.
9
• A new abnormality on chest x-ray should be further assessed with CT. A chest CT should also be
obtained in patients, especially smokers, with concerning symptoms and a normal chest x-ray.
Pathological confirmation of disease is essential before treatment can commence. The choice of which
test is used to gain a tissue sample depends on the location of the lesion to be biopsied. If distant
metastatic disease is suspected on imaging, biopsy of metastatic lesion is recommended in order to
confirm stage at the time of biopsy.
• Procedures for biopsy of lung lesions include flexible bronchoscopy and transthoracic needle
aspiration biopsy:
• Bronchoscopy is performed when CT abnormalities (i.e., a mass or adenopathy) are

accessible to the bronchoscope. It is also used to assess new and/or unexplained
pulmonary symptoms (i.e., haemoptysis, wheezing, cough). Flexible bronchoscopy requires
conscious sedation. During the procedure, the tracheobronchial tree is carefully examined.
Endobronchial tumours can be biopsied. Washings, brushings, and bronchoalveolar lavage
are performed. Suspicious parenchymal lesions and mediastinal lymph nodes that are
accessible can also be biopsied.
• Transthoracic needle aspiration biopsy is often necessary for peripheral lesions that are
inaccessible to bronchoscopy. If a pleural effusion exists, thoracentesis collects cells for
cellular evaluation of malignancy. Ultrasound guidance is helpful for small effusions.
• Method of biopsy for metastatic sites depends on the anatomical location and least invasive
approach.
After a pathological diagnosis has been obtained, further staging studies guide appropriate treatment. All
patients should be evaluated for brain metastases, ideally with a magnetic resonance imaging scan.[5]
• Positron emission tomography (PET)-CT can confirm the extent of intrathoracic disease and
identify distant metastases. PET-CT can also be performed prior to tissue sampling in order to
identify possible metastatic lesion(s) that can be biopsied, determining stage and confirming
pathological diagnosis in the same procedure.
DIAGNOSIS
• Bone scan can detect bone metastasis. However, if staging with PET-CT is performed, bone scan
is unnecessary as PET-CT is more accurate.
• If a pleural effusion is present, it should be evaluated by thoracentesis or thoracoscopy.
• Bone marrow aspiration may be indicated if there are nucleated red cells in the peripheral smear, or
unexplained anaemia or thrombocytopenia.
• Mediastinoscopy is performed to determine node status in patients with a solitary pulmonary
mass without radiographic evidence of lymphadenopathy, as these patients may be candidates for
surgery.
Ancillary studies
A full blood count, chemistry panel, and liver function tests, including alkaline phosphatase, should be
performed in all patients as baseline tests before initiation of treatment and to detect paraneoplastic
syndromes. Examples of paraneoplastic syndromes that are detected by laboratory screening include
syndrome of inappropriate antidiuretic hormone (hyponatraemia), Cushing's syndrome (hyperglycaemia,
hypokalaemia), and cancer-related anaemia. In metastatic disease, alkaline phosphatase levels can be
elevated, indicating potential bone metastases.
All lung cancer patients anticipated to receive chest radiotherapy or surgery should have pulmonary
function tests, including forced expiratory volume in the first second of expiration (FEV₁) and diffusion
capacity of lung for carbon monoxide (DLCO).[30] [31]
History and exam

Key diagnostic factors
presence of risk factors (common)
• Include cigarette smoking and exposure to second-hand tobacco smoke, radon gas, and asbestos.
cough (common)
• A new or persistent cough, especially in a current or former smoker, is suspicious and requires
imaging of the chest.
• Cough is present at diagnosis in over 50% of patients with lung cancer and may be secondary to post-
obstructive pneumonia, endobronchial tumour, or pleural effusion.[4]
dyspnoea (common)
• Present at diagnosis in the majority of patients.[4]
• Possible causes include airway obstruction, underlying COPD, pneumonia, phrenic nerve paralysis, or
a pleural effusion.
haemoptysis (common)
• Occurs in approximately 25% of patients.[4]
• Although massive haemoptysis is rare, patients with lung cancer often cough up blood-tinged sputum.
Haemoptysis in a smoker is suspicious for lung cancer.
chest pain (common)
DIAGNOSIS
• Chest pain or discomfort is present in approximately 33% of patients.[4]
• The lung is devoid of pain fibres. Therefore, most patients with chest pain have tumours that are
invading the pleura or chest wall. However, patients with early disease can present with chest
discomfort.
weight loss (common)

• Cancer-associated cachexia (more common in patients with advanced disease) is an independent
negative prognostic factor and should be specifically evaluated and addressed according to
established practice guidelines.[32]
Other diagnostic factors

age 65 to 74 years (common)
• The median age at diagnosis of lung cancer is 65-74 years.[7] Less than 10% of cases are diagnosed
before 55 years of age.[7]
11
male sex (common)
• More common in men. Age-adjusted incidence in males is 56.4 new cases per 100,000, compared
with 45.3 cases per 100,000 in females (SEER 2016-2020).[7]
fatigue (common)
• Non-specific symptom of lung cancer; often multifactorial.
pulmonary examination abnormalities (common)

• Auscultation of the lungs may demonstrate wheeze, rales, decreased breath sounds, and dullness to
percussion.
hoarseness (uncommon)
• 2% to 18% can present with hoarseness, secondary to recurrent laryngeal nerve paralysis.[4]
confusion (uncommon)
• A common symptom of brain metastases. Up to 40% to 50% of patients with lung cancer develop brain
metastases.[29]
personality changes (uncommon)

• May occur in the setting of brain metastases.
nausea and vomiting (uncommon)

• May indicate brain metastases.
headache (uncommon)
• May indicate brain metastases.
dysphagia (uncommon)
• May occur if tumour has narrowed or obstructed the oesophagus.
DIAGNOSIS
bone pain and/or fractures (uncommon)

• Pain or pathological fractures can result from bone metastases. The axial skeleton and proximal long
bones are most frequently involved.[4]
seizures (uncommon)
• A potential symptom of brain metastases.
cervical or supraclavicular adenopathy (uncommon)

• The most common sites of regional spread are the hilum and mediastinum. The next levels of lymph
node spread are the supraclavicular fossae and cervical chains.
facial swelling (uncommon)

• May indicate compression of the superior vena cava, either from mediastinal adenopathy or from a
right upper lobe tumour extending centrally into the mediastinum.
dilated neck or chest/abdominal wall veins (uncommon)

• Distended neck veins or venous collaterals on the chest or abdominal wall may indicate compression
of the superior vena cava.
finger clubbing (uncommon)
• More common in non-small cell lung cancer than SCLC (35% vs. 4%).[4]
hypertrophic osteoarthropathy (uncommon)

• Painful arthropathy of the wrists, ankles, and knees with periosteal new bone formation. SCLC is a rare
cause.[4]
Risk factors
Strong
cigaret te smoking
• Numerous epidemiological studies link lung cancer and cigarette smoking.[13] [14] [15]
• Tobacco smoke contains multiple carcinogens, including polynuclear aromatic hydrocarbons, aromatic
amines, N-nitrosamines, and other organic and inorganic compounds.[16] Some data suggest that
the presence of COPD may be an independent risk factor for lung cancer development, regardless of
smoking status.[19]
environmental tobacco exposure

• Environmental tobacco smoke (second-hand smoke) is an important cause of lung cancer and
represents one of the risk factors for lung cancer development among never-smokers.[20] Available
data demonstrate that second-hand smoke exposure both in the workplace and in the home is
associated with higher incidence of lung cancer and increased lung-cancer associated mortality.[21]
radon gas exposure

• Uranium is normally found in the earth's crust. Uranium decay produces radon gas, which can
percolate into homes. Radon gas is inert but decays with a half-life of 3.8 days into polonium 214 and
polonium 218. Both substances emit alpha particles, which damage DNA and can lead to malignant
transformation.
DIAGNOSIS
• Numerous case-control studies have associated both occupational (mining) and residential radon
exposure with lung cancer. Radon may contribute up to an estimated 10% of all lung cancer cases.[22]
[23]
Weak
asbestos exposure
• Asbestos fibres are carcinogens that lodge in the lung and are a risk factor for lung cancer, especially
in smokers and heavily exposed people.[24] Epidemiological data have linked asbestos with lung
cancer (all histological variants), whether or not the patient has developed asbestosis - a diffuse
interstitial lung fibrosis secondary to asbestos exposure.[25]
13
Investigations
1st test to order
Test Result
chest x-ray central or peripheral
mass, hilar
• Standard posteroanterior and lateral CXR is an inexpensive
lymphadenopathy,
and simple initial study to evaluate cough, chest pain, and/or
superior mediastinal
haemoptysis.
lymphadenopathy, pleural
effusion
CT chest, liver, and adrenal glands massive

lymphadenopathy and
• A new abnormality on chest x-ray should be further assessed with
direct mediastinal
CT. A chest CT should also be obtained in patients, especially
invasion are common
smokers, with concerning symptoms and a normal chest x-ray.
Intravenous contrast is helpful to distinguish lymph nodes from features of SCLC;
determines extent of
vessels, especially in the hilum.
• Limited disease: involvement restricted to ipsilateral hemithorax within disease
a single radiation port. Extensive disease: presence of contralateral
pulmonary or other distant metastasis.[5]
• After treatment, chest CT (or chest x-ray) can be obtained to evaluate
response to treatment and monitor for disease recurrence.
DIAGNOSIS
Other tests to consider
Test Result
bronchoscopy endobronchial lesions
• Bronchoscopy is performed when CT abnormalities (i.e., a mass
or adenopathy) are accessible to the bronchoscope. It is also used
to assess new and/or unexplained pulmonary symptoms (i.e.,
haemoptysis, wheezing, cough). Flexible bronchoscopy requires
conscious sedation. During the procedure, the tracheobronchial
tree is carefully examined. Endobronchial tumours can be biopsied.
Washings, brushings, and bronchoalveolar lavage are performed.
Suspicious parenchymal lesions and mediastinal lymph nodes that
are accessible can also be biopsied.[33]
• Endobronchial masses can be biopsied with forceps. Endobronchial
brushings, washings, and alveolar lavage increase the diagnostic
yield. Trans-bronchial needle aspiration of accessible parenchymal
lesions and mediastinal lymph nodes is possible.
• Overall, the sensitivity for centrally located lesions is high (about
90%).[33] The sensitivity for peripheral lesions is lower and depends
on number of biopsies taken, size of mass, and proximity to the
bronchial tree. In general, endobronchial biopsy is more sensitive
than brushings or washings.
• Detection of small peripheral lesions (<2 cm) is improved by use of
endobronchial ultrasound.[34]
• Bronchoscopy can be repeated after definitive treatment to assess for
recurrent disease.
biopsy malignant cells,
high nuclear to
• Pathological confirmation of malignancy is the only widely accepted
cytoplasmic ratio, nuclear
method to diagnose lung cancer. Tissue may be sampled with
fragmentation often
bronchoscopy if lesions are central, but specimen adequacy for
diagnosis is variable. Transbronchial biopsy or endobronchial present
biopsy, brushings, and lavage are all used to obtain specimens
during bronchoscopy. CT-guided needle biopsy, where feasible,
allows for core biopsies to obtain sufficient material. If there are
DIAGNOSIS
suspected metastatic lesions, those are preferred sites for diagnostic
biopsy if feasible to confirm metastatic disease. Method of biopsy
for metastatic sites depends on the anatomical location and least
invasive approach.
thoracentesis malignant cells within the
pleural fluid
• Thoracentesis involves placing a needle between the ribs and into
the chest to sample fluid that has accumulated in the pleural space.
Ultrasound is helpful in directing thoracentesis of small pleural
effusions.
thoracoscopy pleural involvement
• May be considered in patients with SCLC and pleural effusion, if
thoracentesis is inconclusive, to determine stage.[5]
MRI or CT of brain brain metastases
appear as enhancing
• All patients with SCLC should be evaluated for brain metastases,
parenchymal masses with
ideally with an MRI.[5]
surrounding oedema
bone scan skeletal metastases

• May be used to identify metastases if PET/CT is not available.[5]
15
Test Result
mediastinoscopy node involvement
• Indicated to determine nodal status in patients with a solitary
pulmonary mass without radiographic evidence of lymphadenopathy,
as these patients may be candidates for surgery. Can also be used
for initial diagnosis.
positron emission tomography (PET) further evaluates location
and extent of primary
• PET is complementary to CT, facilitating accurate assessment of the
tumour; evaluates for
extent of local, regional, and distant disease.[5]
distant metastases
• PET-CT can also be performed prior to tissue sampling in order
to identify possible metastatic lesion(s) that can be biopsied,
determining stage and confirming pathological diagnosis in the same
procedure.
bone marrow aspirate and biopsy bone marrow invasion by
cancer cells
• Indicated for staging in patients who present with nucleated red cells
on peripheral smear, or unexplained anaemia or thrombocytopenia,
and no other evidence of metastatic disease.[5]
FBC usually normal; however,
may show anaemia
• Baseline blood counts are necessary before treatment is initiated or
invasive procedures are performed.
• Chemotherapy, and to a lesser degree radiotherapy, can decrease
haematopoiesis, necessitating baseline and periodic analysis of
blood counts.
LFTs normal or elevated
• Hepatic metastases may cause elevated LFTs.
• Elevated alkaline phosphatase level may indicate bony metastases.
serum sodium lowered
• Hyponatraemia occurs in syndrome of inappropriate antidiuretic
hormone.
renal function usually normal
DIAGNOSIS
• Baseline assessment is recommended before initiation of treatment.

• Some chemotherapy agents, cisplatin in particular, can affect
electrolytes and kidney function.
lung function tests spirometry and lung
volumes
• FEV₁ and diffusion capacity of lung for carbon monoxide (DLCO)
should be performed on all patients expected to receive radiation.[30]
[31]
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Non-small cell lung • Most signs and symptoms • CT chest shows size,
cancer are similar to SCLC. Typical location, and extent of
features include cough, primary tumour; evaluates
haemoptysis, chest pain, for hilar and/or mediastinal
dyspnoea, and hoarseness lymphadenopathy and
(if recurrent laryngeal nerve distant metastases.
paralysis). Weight loss, • Sputum cytology shows
shortness of breath, and characteristic malignant
malaise are other potential cells. Specificity greater than
presenting symptoms. 95%, sensitivity variable
• Finger clubbing between 20% and 70%.
and hypertrophic More likely to be positive with
osteoarthropathy may central lesions compared
be present and are more with peripheral lesions.
common in non-small cell • Pathological sampling
lung cancer compared with for diagnosis may be
SCLC. performed via CT-guided
biopsy or bronchoscopy with
transbronchial biopsy (with
or without endobronchial
ultrasound). Endobronchial
brushings, washings, and
alveolar lavage may also
yield informative material.
Pneumonia/bronchitis • Typical symptoms include • CXR is the first test

fever, cough, dyspnoea, and performed. CT imaging
chest pain. can be helpful to evaluate
• Recurrent pneumonia or pulmonary masses that
bronchitis in a smoker or might not be well visualised
DIAGNOSIS
former smoker should raise with chest x-ray.
the suspicion of lung cancer. • Bronchoscopy can also
be used to assess for
endobronchial lesions or to
biopsy suspicious pulmonary
masses.
Carcinoid tumour • Often asymptomatic with • CT chest: 80% of carcinoid

normal physical examination. tumours appear as an
May cause cough, endobronchial nodule and
dyspnoea, haemoptysis, 20% as a parenchymal
unilateral wheezing, or post- nodule, with smooth,
obstructive pneumonia if rounded borders and highly
tumour is endobronchial or vascularised.
compressing central bronchi. • Flexible bronchoscopy
shows raised, pink,
vascular, lobulated lesions.
Endobronchial forceps
biopsy is usually required for
pathology to be diagnostic;
bronchial brushings, sputum
specimens, and lavage fluid
17

symptoms
rarely provide sufficient
tissue for a conclusive
diagnosis.
Metastatic cancer from a • Signs and symptoms depend • CT chest shows one
non-thoracic primary site on the location of the primary or multiple nodules of
tumour and distant disease variable sizes from diffuse
and may include pain, micronodular opacities
weight loss, malaise, cough, (miliary) to well-defined
dyspnoea, clubbing, or focal masses. Lesions are often
wheezing. Physical findings irregular and in the periphery
may be present depending of the lower lung zones.
on the location and extent of • CT/MRI head, CT abdomen
the disease. and pelvis: extrapulmonary
cancers that commonly
metastasise to the lung
include melanoma;
thyroid carcinoma;
oesophageal cancer; ovarian
cancer; sarcomas; and
adenocarcinomas of the
colon, breast, kidney, and
testis.
• PET-fluorodeoxyglucose
(FDG) scan shows increased
uptake in both primary
and distant sites. Certain
metastatic lesions, such as
renal cell carcinoma, have a
lower probability of 18-FDG
uptake.
• CT-guided transthoracic
needle aspiration
DIAGNOSIS
(TTNA) can reveal

characteristic malignant
cells. Pneumothorax
complicates 20% to 30%
of TTNA procedures.
The choice between
bronchoscopy and TTNA
is based on lesion size,
location, risks, and local
expertise.
• Biopsy during flexible
bronchoscopy and
biopsy may show
characteristic malignant
cells. Bronchoscopy has a
100% yield for endobronchial
lesions (which are extremely
rare in metastatic deposits
from other primary tumours).
Infectious granuloma • History may include travel • CT-guided transthoracic

to endemic areas, pet/ needle aspiration (TTNA)
animal exposures, and can be used for diagnostic

symptoms
specific leisure activities sampling. Pneumothorax
(e.g., caving). complicates 20% to 30%
• May feature cough, of TTNA procedures.
dyspnoea, haemoptysis, The choice between
weight loss, fever, joint bronchoscopy and TTNA
aches, skin lesions, is based on lesion size,
and night sweats, or location, risks, and local
no symptoms. Many expertise.
possible causes: • CT chest typically shows
Histoplasma capsulatum lesions <2 cm diameter
, Mycobacterium and round with smooth
tuberculosis , Coccidioides borders. Old granulomatous
immitis , Cryptococcus disease may feature
neoformans , Aspergillus central, laminated, or
, Pseudallescheria boydii diffuse calcification
, Fusarium species, patterns. Mediastinal
zygomycetes, and others. lymphadenopathy without
• Non-specific skin calcifications is sometimes
findings may be seen in present. Nodules from
atypical mycobacteria angioinvasive fungi
and cryptococcosis. (e.g., Aspergillus ,
Lymphadenopathy may be Pseudallescheria boydii
present with active disease. , Fusarium species,
and zygomycetes) may
demonstrate the 'halo
sign' (ground-glass opacity
surrounding the nodule).
Occasionally, calcifications
can be seen in the spleen or
liver.
• Fungal serologies: positive
during active infection.
The exact role of fungal
DIAGNOSIS
serologies in assessing
lung nodules is unclear.
However, they provide
valuable evidence of
exposure to histoplasmosis,
cryptococcosis, aspergillosis,
coccidioidomycosis, and
mucormycosis.
• Flexible bronchoscopy
and biopsy can sometimes
provide samples for
identification and culture and
sensitivity of the organism.
• PET: usually negative (<2.5
standardised uptake values).
May be positive in active
infectious processes.
Sarcoidosis • Cough, dyspnoea, fatigue, • CT chest: mediastinal

weight loss, fever, night adenopathy often present
sweats, rash, eye pain, with sarcoid. Sarcoid
photophobia, blurred vision, nodules have predilection for
and red eye. Pulmonary upper zones, although can
19

symptoms
examination is usually be located throughout the
unrevealing. Can affect lung.
any organ, so physical • Flexible bronchoscopy and
findings depend on specific biopsy can demonstrate
organs affected. Skin lesions presence of non-caseating
including maculopapular granulomas. The
eruptions, subcutaneous identification of granulomas
nodular lesions, and red- on tissue obtained by
purple skin lesions. bronchoscopy should be
performed by a pathologist
and stained for infectious
agents before assuming a
non-infectious cause.
needle aspiration (TTNA)
can provide access to
material from some
lesions inaccessible to
flexible bronchoscopy. The
identification of granulomas
on tissue obtained by TTNA
should be performed by a
pathologist and stained for
infectious agents before
assuming a non-infectious
cause.
• Laboratory markers: ACE
elevation may be seen
in sarcoidosis but is non-
specific.
Rheumatoid arthritis • Arthralgias, pain, skin • CT chest typically shows

nodules, pleural effusions, lung nodule 3 mm to 7 cm,
DIAGNOSIS
pleuritis, joint pain, and predominantly in peripheral

deformity. upper and mid-lung zones.
May show cavitation.
• Flexible bronchoscopy and
biopsy shows rheumatoid
necrobiotic nodule. The
identification of granulomas
on tissue obtained should be
performed by a pathologist
and stained for infectious
agents before assuming
a non-infectious cause.
Necrobiotic nodules
demonstrate a central zone
of eosinophilic fibrinoid
necrosis surrounded by
palisading fibroblasts, the
nodule often centred on
necrotic inflamed blood
vessels.
• Laboratory markers: patients
with lung nodules due
to rheumatoid arthritis

symptoms
frequently have high levels of
rheumatoid factor, although
seronegative cases have
been reported.
Granulomatosis with • Cough, chest pain, • CT chest shows solitary

polyangiitis (formerly dyspnoea, haemoptysis, or multiple lung nodules.
known as Wegener's rhinorrhoea, epistaxis, ear/ Airways are frequently
granulomatosis) sinus pain, hoarseness, affected.
fever, fatigue, anorexia, • Flexible bronchoscopy or
weight loss, palpable CT-guided transthoracic
purpura, painful ulcers, needle aspiration (TTNA)
uveitis, upper airway may show necrotising
inflammation, and sinus granulomatous inflammation.
pain. The identification of
granulomas on tissue
obtained by bronchoscopy or
TTNA should be performed
by a pathologist and stained
for infectious agents before
assuming a non-infectious
cause.
• Laboratory markers: anti-
neutrophil cytoplasmic
antibody (ANCA). ANCA
testing results depend on
the extent and severity of
the disease. Generalised
granulomatosis with
polyangiitis demonstrates
>90% C-ANCA or
PR-3 positivity. Limited
granulomatosis with
DIAGNOSIS
polyangiitis demonstrates
60% ANCA positivity.
Hamartoma • Usually asymptomatic • CT chest shows well-

with no physical findings. demarcated peripheral
One percent to 20% of nodule, with an average
lesions are endobronchial diameter of 1.5 cm and a
and can cause dyspnoea, heterogeneous appearance
wheezing, or recurrent due to its content of
infections, secondary to mesenchymal tissue content.
airway obstruction. Fat attenuation is common,
with or without calcification.
'Popcorn' calcifications can
occur in 20% of cases.
Imaging findings are classic
and considered diagnostic.
needle aspiration may
be used for diagnostic
sampling.
21

symptoms
Arteriovenous • Dyspnoea is uncommon. • CT chest shows round or
malformation (AVM) May cause haemoptysis, oval nodule(s) ranging from
pulmonary bruit, 1 cm to several centimetres
arteriovenous in diameter. Feeding artery
communications, or and draining vein often
haemorrhagic telangiectasia identified. Most common in
in the skin, mucous lower lobes. Multiple lesions
membranes, and other in 30% of cases.
organs. Cyanosis and finger • Pulmonary angiography
clubbing may be present. confirms presence and
Neurological symptoms from location of AVMs, identifies
cerebral aneurysms, cerebral feeding arterial and venous
emboli. structures. In cases of
significant haemoptysis,
pulmonary angiogram is
combined with bronchial
artery embolisation.
• Arterial blood gas analysis
may show decreased pO₂
and decreased oxygen
saturation when arterial to
venous flow is severe. In
cases of severe systemic
AVMs, chronic hypoxaemia
may cause polycythemia.
Amyloidosis • Weight loss, paraesthesias, • CT chest shows lung

dyspnoea, and fatigue are involvement characterised
the most common symptoms by focal pulmonary nodules,
associated with amyloidosis tracheobronchial lesions, or
and are common to all diffuse alveolar deposits.
systemic forms. • Serum immunofixation
• Weight loss of >9 kg is shows presence of
DIAGNOSIS
common. Small vessel monoclonal protein; seen

involvement can cause in 60% of patients with
jaw or limb claudication, immunoglobulin light chain
and rarely angina. Amyloid amyloidosis (AL).
purpura is present in about • Urine immunofixation shows
1 in 6 patients, typically peri- presence of monoclonal
orbital. Eyelid petechiae are protein; seen in 80% of
common. Hepatomegaly >5 patients with amyloidosis.
cm below the right costal • Immunoglobulin free light
margin is seen in 10% of chain assay shows abnormal
patients and splenomegaly is kappa to lambda ratio.
usually of modest degree. This relatively new test has
extremely high sensitivity,
over 90%, for diagnosing
amyloidosis.
Bronchiolitis obliterans • Normally presents as a flu- • CT chest is preferable to

organising pneumonia like illness followed by a plain chest x-ray as it gives
second illness lasting 1 to a better assessment of
4 months, with low-grade the disease pattern and
fever, non-productive cough, distribution, and potential
malaise, dyspnoea, and sites for biopsy. Typical

symptoms
weight loss. Sometimes features include: patchy
features pleuritic chest pain 'ground-glass' opacities
and haemoptysis. in a sub-pleural and/
• In most patients, or peribronchovascular
auscultation reveals fine, distribution; thickening
dry lung crackles. Finger of bronchial walls and
clubbing is unusual. cylindrical dilation; 3 to 5
mm diameter centrilobular
nodules or other ill-defined
nodules; mediastinal
lymphadenopathy, pleural
effusions.
• Pulmonary function tests
typically show a restrictive
pattern.
• Bronchoalveolar lavage
(BAL) shows a mixed cell
pattern, with an increase in
lymphocytes, neutrophils,
eosinophils, mast cells,
foamy macrophages, and
occasional plasma cells.
CD4+/CD8+ cell ratio is
decreased. Also, the ratio of
lymphocytes to CD8+ cells is
significantly increased.
• Transbronchial lung biopsy,
in combination with BAL, can
be a useful approach, prior
to possible open biopsy.
• Open lung biopsy is often
required for definitive
diagnosis.
DIAGNOSIS
Pulmonary tuberculosis • Cough longer than 2 to • Chest x-ray: primary disease
3 weeks, discoloured or commonly presents as
bloody sputum, night sweats, middle and lower lung
weight loss, loss of appetite, zone infiltrates. Ipsilateral
pleuritic chest pain. adenopathy, atelectasis
from airway compression,
and pleural effusion can
be seen. Reactivation-type
(post-primary) pulmonary
tuberculosis usually involves
apical and/or posterior
segment of right upper lobe,
apicoposterior segment of
left upper lobe, or superior
segment of either lower lobe,
with or without cavitation.
As disease progresses it
spreads to other segments/
lobes.
• Sputum smear: positive
for acid-fast bacilli
(AFB). Sputum may be
23

symptoms
spontaneously expectorated
or induced, and at least
3 specimens should be
collected (minimum 8
hours apart, including an
early morning specimen,
which is the best way to
detect Mycobacterium
tuberculosis ). Organisms
other than M tuberculosis ,
especially non-tuberculous
mycobacteria (e.g.,
Mycobacterium kansasii and
Mycobacterium avium ), may
be positive for AFB stain.
• Nucleic acid amplification
tests (NAAT): positive for M
tuberculosis . DNA or RNA
amplification tests for rapid
diagnosis. May be used on
sputum or any sterile body
fluid. Several commercial
tests are available. Results
available in less than 8
hours in the laboratory.
Useful in smear-positive
disease to confirm that
observed mycobacteria
are M tuberculosis (95%
sensitivity, 99% specificity)
and in smear-negative
disease for rapid diagnosis
(50% sensitivity, 95%
DIAGNOSIS
specificity). In suspected
smear-negative cases, a
moderate to high pretest
probability should guide the
decision to use NAAT.
Germ cell tumour • Occur mostly in men aged • CT chest: germ cell tumours
20 to 40 years. About account for about 10%
one third of patients are to 15% of mediastinal
asymptomatic. Symptoms tumours in adults and
are related to the size of 25% of such tumours in
the lesion. May cause chest children. Frequently located
pain, breathing problems, in anterior mediastinum. CT
cough, fever, headache, and can determine if mass is
fatigue. cystic or solid and whether
it contains calcium or fat.
Contrast enhancement
provides information
concerning vascularisation
of the mass and relationship
to adjacent structures.
Seminomas appear as
large, well-marginated,

symptoms
homogeneous, anterior
mediastinal mass with soft-
tissue opacity or attenuation
that shows minimal contrast
enhancement.
• Serum tumour marker tests:
alpha-fetoprotein (AFP),
beta-human chorionic
gonadotrophin (beta-hCG),
lactate dehydrogenase
(LDH). beta-hCG levels are
elevated in 7% to 18% of
patients. AFP levels are
usually normal.
Non-Hodgkin's lymphoma • Aggressive non-Hodgkin's • CT chest: frequently anterior

lymphoma (NHL) may mediastinum. Can determine
present with fever, drenching if mass is cystic or solid
night sweats, malaise, and whether it contains
weight loss, cough, calcium or fat. Contrast
shortness of breath, enhancement provides
abdominal discomfort, information concerning
headache, change in vascularisation of the mass
mental status, dizziness, and relationship to adjacent
ataxia, pleural effusion, structures.
lymphadenopathy, • FBC with differential:
pallor, purpura, shows thrombocytopenia,
jaundice, hepatomegaly, pancytopenia.
splenomegaly, skin • Blood smear: shows
nodules, and abnormal nucleated red blood cells,
neurological examination. giant platelets.
Low-grade NHL patients • Lymph node biopsy with
often minimally symptomatic immunohistochemistry:
DIAGNOSIS
or asymptomatic. shows characteristic cells.
Preferably obtain excisional
or core biopsy to provide
information on lymph node
architecture.
• Mediastinoscopy: used to
sample mediastinal nodes.
Hodgkin's lymphoma • Predominantly a disease of • Plain chest x-ray: typically

young adults. Most patients shows mediastinal
present with a several- mass/large mediastinal
month history of persistent adenopathy.
adenopathy, most commonly • PET scan: involved sites
of the cervical chain. appear fluorodeoxyglucose
(FDG)-avid (bright) with PET
imaging. Sensitivity reported
to be 93% and specificity
87%.
• Lymph node biopsy with
immunohistochemistry:
the Hodgkin's cell can be
a characteristic Reed-
Sternberg cell, or one of
25

symptoms
its variants, such as the
lacunar cell in the nodular
sclerosis subtype; in nodular
lymphocyte-predominant
Hodgkin's lymphoma, the
characteristic cell is the
lymphocytic and histiocytic
(L&H) cell, also referred to
as a popcorn cell.
Thymoma/thymic • Approximately 30% of • Plain chest x-ray: in 50%

carcinoma patients with thymoma of the patients, thymomas
are asymptomatic at the are detected by chance with
time of diagnosis. May plain-film chest radiography.
also present with cough, • CT chest: 90% occur in
chest pain, signs of upper anterior mediastinum. CT is
airway congestion, superior usually accurate in predicting
vena cava syndrome, tumour size; location;
dysphagia, or hoarseness. and invasion into vessels,
May have features of the pericardium, and the
paraneoplastic syndromes lung. However, it cannot
associated with thymoma accurately predict invasion or
including myasthenia resectability.
gravis, polymyositis, lupus • PET scan: may be of value
erythematosus, rheumatoid in determining malignancy
arthritis, thyroiditis, and and extramediastinal
Sjogren's syndrome. About involvement.
30% of patients have • Pre-operative biopsy:
symptoms suggestive of indicated if there are
myasthenia gravis (e.g., atypical features or if
ptosis, double vision). imaging suggests invasive
tumour and patient is under
consideration for induction
DIAGNOSIS
therapy.
Bronchogenic cyst • Usually diagnosed in • Two-view chest radiography:

infancy and childhood, typically shows a sharply
although 50% are diagnosed demarcated spherical
after 15 years of age. mass of variable size, most
Approximately 50% of commonly located in the
patients are asymptomatic. middle mediastinum around
In adults, chest pain (often the carina. Can appear as a
pleuritic) and dysphagia solid tumour or show air-fluid
(due to oesophageal level if the cyst is infected or
compression) are the most contains secretions.
common symptoms. May • CT chest: frequently middle
also feature recurrent mediastinum, typically at the
cough and chest infection/ level of the mediastinum.
pneumonia, superior Cysts are thin-walled with
vena cava syndrome, smooth borders and may
tracheal compression, and contain secretions, blood, or
pneumothorax. pus. Calcifications may also
be seen.
• MRI: frequently middle
mediastinum, typically at the
level of the mediastinum.

symptoms
T2-weighted images show
a homogeneous mass of
moderate-to-bright intensity.
On T1-weighted images,
lesions may vary in intensity
depending on protein content
of the cyst.
Tracheal tumours • Common symptoms • Plain chest radiographs

include dyspnoea, cough, are generally insensitive
haemoptysis, wheeze, and for detection of tracheal
stridor. Less commonly, tumours. Clues that may
hoarseness and dysphagia indicate the presence of
may be present. a tracheal tumour include
abnormal calcification,
tracheal narrowing, and post-
obstructive pneumonia or
atelectasis.
• Helical CT enables accurate
calculation of tumour
volumes and can help
differentiate mucosal lesions
from submucosal lesions.
• MRI can be useful in
assessing extension into
surrounding tissue and
vascular anatomy.
• Bronchoscopy allows direct
visualisation, opportunity
for biopsy, and potential for
laser treatment.
Thyroid mass • Symptoms and signs depend • Laboratory testing should
DIAGNOSIS
on size of mass. May be include thyroid function
visible/palpable as a lump panel, with thyroid-
on the anterior aspect of stimulating hormone, free
the neck. May present with T4, free T3.
dysphagia, hoarseness, • I-123 thyroid scan is ordered
difficulty breathing, and pain for patients with overt or
in neck or throat. May also subclinical hyperthyroidism.
be signs and symptoms of A hyperfunctioning (hot)
hyper- or hypothyroidism nodule is almost always
depending on the nature of benign. Most nodules are
the mass. hypofunctioning (cold). Most
of these are benign, but
malignant nodules are also
cold.
• Ultrasound and Doppler
can be used to define
dimensions of thyroid
nodules and solid/cystic
component(s). Features
suspicious of malignancy
include microcalcifications,
a more tall-than-wide
shape, hypervascularity,
27

symptoms
marked hypoechogenicity, or
irregular margins. It can also
guide fine-needle aspiration,
which can reveal malignant
cells or cyst fluid.
• CT neck can evaluate
cervical lymph nodes in
cases of medullary thyroid
cancer, and extension of
the scan into the chest can
help evaluate a retrosternal
thyroid mass.
Criteria
Veterans Administration Lung Cancer Study Group: small cell lung
cancer[35] [36]
Older and more common staging system for small cell lung cancer.
• Limited stage: disease confined to the ipsilateral hemithorax, which can be safely encompassed within
a tolerable radiation field.
• Extensive stage: all other disease, including metastatic disease and malignant pleural/pericardial
effusions.
American Joint Commit tee on Cancer staging (8th edition, 2017):

small cell lung cancer[37]
DIAGNOSIS
The American Joint Committee on Cancer staging system describes the extent of disease based on the
following anatomic factors: size and extent of the primary tumour (T); regional lymph node involvement (N);
and presence or absence of distant metastases (M).[37]
Screening
Recommendations
The US Preventive Services Task Force (USPSTF) and the American College of Radiology recommend
annual low-dose computed tomography (CT) in:[38] [39]
• Adults aged 50 to 80 years, with
• At least a 20 pack-year smoking history, who
• Currently smoke or have quit within the past 15 years.

The National Comprehensive Cancer Network recommends screening for lung cancer with low-dose CT in
high-risk adults:[40]
• Aged ≥50 years, with
• ≥20 pack-year history of smoking.
Shared decision-making is recommended in candidates for screening, including a discussion of the benefits
and risks involved.
In creating screening recommendations, reduction in lung cancer mortality must be balanced against harms
from positive screening results and over-diagnosis, as well as against costs. Screening may be less useful
in detecting early-stage SCLC than early-stage non-small cell lung cancers (NSCLC), likely because of the
aggressive nature of SCLC, and because it is less common than NSCLC.[39]
Evidence from randomised screening trials

The National Lung Screening Trial, sponsored by the National Cancer Institute, randomised more than
53,000 current or former smokers to 3 annual screening sessions with chest x-ray (CXR) or low-dose
helical CT. Participants were between 55 and 74 years of age and had at least 30 pack-years of smoking.
Participants who received CT scans had a 20% lower risk of dying from lung cancer than those who
underwent screening with CXR, and a 7% lower risk of death from any cause. The number needed to
screen with low-dose CT to prevent one death from lung cancer was 320. The risk of death associated with
diagnostic procedures triggered by screening was low.[41]
The smaller Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) study randomly assigned
13,195 men (with a later subgroup analysis of 2594 women) between the ages of 50 and 74 years with
previous or current smoking history to undergo yearly CT screening at baseline and 1, 3, and 5.5 years.[42]
The NELSON study showed that screening resulted in a 24% reduction in lung cancer mortality and a 6.7%
reduction in overall mortality.
DIAGNOSIS
29
Small cell lung cancer Management
Approach
Treatment regimens vary depending on stage of cancer.[5]
• Limited stage: disease confined to the ipsilateral hemithorax, which can be safely encompassed within
a tolerable radiation field.
• Extensive stage: all other disease, including metastatic disease and malignant pleural/pericardial
effusions.
There are many variations and combinations of factors involved in the assessment of each patient. Care of
patients with lung cancer should be undertaken by a multidisciplinary team in a specialised oncology centre.
Limited disease
Patients with limited-stage SCLC are treated with concurrent chemotherapy and radiotherapy (RT).[43]
[44] Chemotherapy typically consists of cisplatin and etoposide, although carboplatin is occasionally
substituted for cisplatin.[5] Concurrent RT is recommended.[43] [44] Early RT (given with cycle 1 or 2 of
chemotherapy) is preferred to RT administered later in the chemotherapy course.[44] [45] Twice-daily
radiation dosing (45 Gy in 1.5-Gy fractions) is preferred though once-daily dosing (approximately 60-70
Gy in 2-Gy fractions) may be acceptable if twice-daily dosing is not feasible.[46] [47] [48]
Surgical intervention has limited use in SCLC because most patients present with advanced disease.
For the rare patient with a solitary pulmonary mass without radiographical evidence of lymphadenopathy,
it is recommended that preoperative mediastinoscopy be performed to confirm N0 status. For these
patients, surgical resection, typically a lobectomy, is reasonable. Postoperative chemotherapy should then
be administered. Patients with resected limited-stage SCLC with N2 status should receive mediastinal
radiation in addition to chemotherapy; postoperative radiation may be considered in patients with N1
status.[5] [49]
Lobectomy involves division of the lobar pulmonary arteries, pulmonary veins, the associated bronchus,
and hilar lymph nodes, and removal en bloc. Access to the chest is usually via a thoracotomy, although
minimally invasive techniques (i.e., video-assisted thorascopic surgery) are gaining favour due to shorter
hospitalisations and less postoperative pain. Sampling or dissection of mediastinal lymph nodes is
recommended.
US guidelines recommend preoperative exercise for people undergoing surgery for lung cancer, as it can
lead to a shorter hospital stay and reduced risk of postoperative complications.[50] The guidelines also
recommend aerobic and resistance exercise during treatment with curative intent in order to reduce the
adverse effects of treatment.[50]
See Non-small cell lung cancer for further surgical details.
Extensive disease
Patients with extensive-stage SCLC typically receive chemotherapy plus immunotherapy for 4 to 6 cycles
followed by maintenance immunotherapy until disease progression or unacceptable toxicities.[5][51]
MANAGEMENT
[52] Commonly used regimens include cisplatin plus etoposide plus durvalumab, or carboplatin plus
etoposide plus either atezolizumab or durvalumab. Atezolizumab or durvalumab can be omitted if there
are contraindications to immune checkpoint inhibitors. Cisplatin or carboplatin plus irinotecan is an
additional option.
Atezolizumab and durvalumab are immunotherapeutic agents that have different mechanisms of action
compared with cytotoxic chemotherapy.[51] [53] These immune checkpoint inhibitors can cause unique
immune-mediated adverse events that are not seen with traditional cytotoxic chemotherapy, such as
pneumonitis, colitis, dermatitis, myositis, and hypothyroidism, among others. Awareness of the array of
possible immune-mediated adverse events by both provider and patient is critical for early recognition, as
well as potential drug to drug interactions.[54] [55]
Of note, maintenance treatment with combination immunotherapy (nivolumab plus ipilimumab) did not
improve overall survival compared with single-agent immunotherapy and therefore is not recommended in
the first-line setting.[56]
RT can be used to palliate symptomatic sites including the lung, bone, and brain. Patients with limited
sites of metastatic disease who achieve a complete extrathoracic response and at least a partial
intrathoracic response to initial chemotherapy can be considered for thoracic RT to delay or prevent
recurrent symptomatic disease.[44] [57] [58]
Prophylactic cranial irradiation (PCI)

Patients with SCLC are at high risk of developing brain metastases. Randomised trials have demonstrated
a survival benefit for PCI in patients who respond to initial therapy. The data are stronger in limited-stage
disease than in extensive-stage disease.[44] [59] [60]
Studies have tried to clarify the potential benefit of PCI in extensive-stage SCLC. A randomised trial
comparing PCI to observation was performed in extensive-stage SCLC patients and showed a lower
incidence of symptomatic brain metastases and increased disease-free survival and overall survival
in the PCI group; however, this study has been criticised as patients were not required to have a brain
magnetic resonance imaging (MRI) scan at screening, and therefore it is unclear whether patients were
receiving PCI or therapeutic radiation.[61] One randomised study comparing PCI with observation (MRI
surveillance) in extensive-stage disease was stopped early for futility, and while there was a decrease
in incidence of brain metastases, overall survival was worse, although not statistically significant, with
PCI.[59]
Among patients receiving PCI, the recommended dose is 25 Gy in 2.5-Gy fractions. One randomised
trial found no difference in 2-year incidence of brain metastasis between 25-Gy and 36-Gy regimens,
but there was increased toxicity with the higher dose.[62] [63] PCI is not recommended in patients
with poor performance status or impaired mental function. Depending on patient- and disease-specific
characteristics, routine surveillance with MRI brain may be an alternative to PCI.[44]
Relapse
National Comprehensive Cancer Network (NCCN) guidelines recommend platinum-based regimens
as subsequent systemic therapy for patients who relapse.[5] One meta-analysis of observational and
randomised study data found that platinum-doublet chemotherapy was associated with a significantly
higher objective response rate and disease control rate in patients with relapsed SCLC compared with
non-platinum-based regimens.[64]
MANAGEMENT
The original or a similar platinum-containing regimen is recommended for patients who remain disease-
free for >6 months.[5]
31
Consideration may be given to the original, or a similar, platinum-based regimen for patients with early
relapse (within 6 months).[5] However, these patients are regarded as having resistant or refractory
disease; response to subsequent therapy is poor and a clinical trial may be the preferred option.
Single-agent immune checkpoint inhibitors (nivolumab, pembrolizumab) are listed as other treatment
options for relapsed SCLC.[5] Nivolumab, however, did not improve survival versus chemotherapy in a
randomised open-label phase III trial of relapsed SCLC.[65]
The use of immune checkpoint inhibitors in patients with disease progression while receiving
maintenance atezolizumab or durvalumab is discouraged.[5]
The choice between the many regimens is complex and needs to be managed in a specialised oncology
centre. There are numerous chemotherapy drugs and combinations that may be used if a clinical trial is
not feasible, although response rates are low. All have the potential to cause bone marrow suppression,
nausea/vomiting, alopecia, and fatigue. Other adverse effects are specific to the particular agent.
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute ( summary )
at initial presentation: limited
disease
1st chemotherapy
plus radiotherapy
plus prophylactic cranial irradiation
adjunct surgery
at initial presentation: extensive

disease
1st chemotherapy ± immunotherapy
plus prophylactic cranial irradiation or routine

surveillance with MRI brain
adjunct radiotherapy
Ongoing ( summary )
relapse within 6 months
MANAGEMENT
1st systemic therapy or radiotherapy
relapse after 6 months
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute
at initial presentation: limited
disease
1st chemotherapy
Primary options
» cisplatin
-and-
» etoposide
Secondary options
» carboplatin
-and-
» etoposide
» The choice between the many

chemotherapeutic regimens is complex and
needs to be managed in a specialised oncology
centre.
» For patients with limited-stage SCLC,

chemotherapy combined with radiotherapy is
standard.[43] [44] National Comprehensive
Cancer Network guidelines recommend
cisplatin and etoposide, although the guidelines
acknowledge that carboplatin is often substituted
for cisplatin in clinical practice.[5]
» All chemotherapy agents have the potential

to cause bone marrow suppression, nausea/
vomiting, alopecia, and fatigue. Other adverse
effects are specific to the particular agent.
» See local specialist protocol for dosing

guidelines.
plus radiotherapy
Treatment recommended for ALL patients in
selected patient group
» Radiotherapy (RT) is standard in patients
with limited-stage SCLC and early RT (given
with cycle 1 or 2 of chemotherapy) is preferred
to RT administered later in the chemotherapy
course.[44] [45]
MANAGEMENT
» Twice-daily radiation dosing (45 Gy in 1.5-

Gy fractions) is preferred though once-daily
dosing (approximately 60-70 Gy in 2-Gy
fractions) is acceptable if twice-daily dosing is
not feasible.[46] [47] [48]
33
Acute
» RT is effective in palliating symptoms
of advanced intrathoracic disease (i.e.,
haemoptysis, chest pain, shortness of breath) as
well as symptomatic metastatic sites (e.g., bone
and brain metastases).
» Adverse effects depend on the size of the

radiation field, the dose, and the adjacent organs
(the lungs and oesophagus, in particular), which
unavoidably receive some radiation.
» The most common adverse effects are

fatigue, skin erythema/desquamation, and
oesophagitis. Most patients develop some
degree of oesophagitis during treatment. The
most common late complication is pneumonitis,
which is characterised by dyspnoea, dry
cough, and fever occurring 1 to 6 months after
completing treatment. Pneumonitis is rarely
fatal. Most patients develop some degree
of lung fibrosis after RT, but this is usually
asymptomatic. Rare complications include
oesophageal stricture and bronchial stenosis,
which are more common when higher doses of
radiation are prescribed.[30] [66] [67]
plus prophylactic cranial irradiation
» Patients with SCLC are at high risk of
developing brain metastases. Randomised
trials have demonstrated a survival benefit
for prophylactic cranial irradiation (PCI) in
patients who respond to initial therapy. The data
are stronger in limited-stage disease than in
extensive-stage disease.[44] [59] [60]
» Among patients receiving PCI, the

recommended dose is 25 Gy in 2.5-Gy
fractions.[62] [63]
adjunct surgery
Treatment recommended for SOME patients in
» Surgical intervention has limited use in SCLC
because most patients present with advanced
disease. For the rare patient with a solitary
pulmonary mass without radiographical evidence
of lymphadenopathy, it is recommended that
preoperative mediastinoscopy be performed
MANAGEMENT
to confirm N0 status. For these patients,

surgical resection, typically a lobectomy, is
reasonable. Postoperative chemotherapy should
then be administered. Patients with resected
limited-stage SCLC with N2 status should
receive mediastinal radiation in addition to
Acute
chemotherapy; postoperative radiation may be
considered in patients with N1 status.[5] [49]
» Lobectomy involves division of the lobar

pulmonary arteries, pulmonary veins, the
associated bronchus, hilar lymph nodes, and
removal en bloc. Access to the chest is usually
via a thoracotomy, although minimally invasive
techniques (i.e., video-assisted thorascopic
surgery) are gaining favour due to shorter
hospitalisations and less postoperative pain.
Sampling or dissection of mediastinal lymph
nodes is recommended.
» US guidelines recommend preoperative

exercise for people undergoing surgery
for lung cancer, as it can lead to a shorter
hospital stay and reduced risk of postoperative
complications.[50] The guidelines also
recommend aerobic and resistance exercise
during treatment with curative intent in order to
reduce the adverse effects of treatment.[50]
» See Non-small cell lung cancer for further

surgical details.
at initial presentation: extensive
disease
1st chemotherapy ± immunotherapy

Primary options
» carboplatin
--AND--
» etoposide
--AND--
» atezolizumab
-or-
» durvalumab
OR
» cisplatin
-and-
» etoposide
-and-
» durvalumab
OR
MANAGEMENT
» cisplatin
-or-
» carboplatin
--AND--
» irinotecan
35
Acute
» Patients with extensive-stage SCLC typically
receive chemotherapy plus immunotherapy
for 4 to 6 cycles followed by maintenance
immunotherapy until disease progression or
unacceptable toxicities.[5] [51] [52] Numerous
chemotherapy drugs and combinations are in
use. Commonly used regimens include cisplatin
plus etoposide plus durvalumab, or carboplatin
plus etoposide plus either atezolizumab or
durvalumab.
» Atezolizumab and durvalumab are

immunotherapeutic agents that have different
mechanisms of action compared with cytotoxic
chemotherapy.[51] [53] These immune
checkpoint inhibitors can cause unique immune-
mediated adverse events that are not seen with
traditional cytotoxic chemotherapy, such as
pneumonitis, colitis, dermatitis, myositis, and
hypothyroidism, among others. Awareness of
the array of possible immune-mediated adverse
events by both provider and patient is critical for
early recognition, as well as potential drug to
drug interactions.[54] [55]
» Atezolizumab or durvalumab can be omitted

if there are contraindications to immune
checkpoint inhibitors. Cisplatin or carboplatin
plus irinotecan is an additional option.
» All listed chemotherapeutic treatments have

the potential to cause bone marrow suppression,
nausea/vomiting, alopecia, and fatigue. Other
adverse effects are specific to the particular
agent. See local specialist protocol for dosing
guidelines.
plus prophylactic cranial irradiation or routine
surveillance with MRI brain
» Patients with SCLC are at high risk of
developing brain metastases. Randomised
trials have demonstrated a survival benefit
for prophylactic cranial irradiation (PCI) in
patients who respond to initial therapy. The data
are stronger in limited-stage disease than in
extensive-stage disease.[44] [59] [60]
» Among patients receiving PCI, the

recommended dose is 25 Gy in 2.5-Gy
MANAGEMENT
fractions.[62] [63]
» Depending on patient- and disease-specific

characteristics, routine surveillance with a
magnetic resonance imaging (MRI) scan of the
brain may be an alternative to PCI.[44]
Acute
adjunct radiotherapy
Treatment recommended for SOME patients in
» Radiotherapy (RT) is effective in palliating
symptoms of advanced intrathoracic disease
(i.e., haemoptysis, chest pain, shortness of
breath) as well as symptomatic metastatic sites
(e.g., bone and brain metastases).
» Patients with limited sites of metastatic disease

who achieve a complete extrathoracic response
and at least a partial intrathoracic response
to initial chemotherapy can be considered
for thoracic RT to delay or prevent recurrent
symptomatic disease.[44] [57] [58]
» Adverse effects depend on the size of the

radiation field, the dose, and the adjacent organs
(the lungs and oesophagus, in particular), which
unavoidably receive some radiation.
» The most common adverse effects are

fatigue, skin erythema/desquamation, and
oesophagitis. Most patients develop some
degree of oesophagitis during treatment. The
most common late complication is pneumonitis,
which is characterised by dyspnoea, dry
cough, and fever occurring 1 to 6 months after
completing treatment. Pneumonitis is rarely
fatal. Most patients develop some degree
of lung fibrosis after RT, but this is usually
asymptomatic. Rare complications include
oesophageal stricture and bronchial stenosis,
which are more common when higher doses of
radiation are prescribed.[30] [66] [67]
MANAGEMENT
37
Ongoing
relapse within 6 months

Primary options
» cisplatin
-or-
» carboplatin
--AND--
» etoposide
OR
» cisplatin
-or-
» carboplatin
--AND--
» irinotecan
Secondary options
» topotecan
OR
» lurbinectedin
OR
» paclitaxel
OR
» docetaxel
OR
» temozolomide
OR
» etoposide
OR
» irinotecan
MANAGEMENT
OR
» gemcitabine
OR
Ongoing
» cyclophosphamide
-and-
» doxorubicin
-and-
» vincristine
OR
» bendamustine
OR
» vinorelbine
Tertiary options
» nivolumab
OR
» pembrolizumab
» National Comprehensive Cancer Network

(NCCN) guidelines recommend platinum-based
regimens as subsequent systemic therapy for
patients who relapse.[5] One meta-analysis
of observational and randomised study data
found that platinum-doublet chemotherapy was
associated with a significantly higher objective
response rate and disease control rate in
patients with relapsed SCLC compared with non-
platinum-based regimens.[64]
» Consideration may be given to the original, or

a similar, platinum-based regimen for patients
with early relapse (within 6 months).[5] However,
these patients are regarded as having resistant
or refractory disease; response to subsequent
therapy is poor and a clinical trial may be the
preferred option.
» The choice between the many regimens

is complex and needs to be managed in a
specialised oncology centre.
» There are numerous chemotherapy drugs and

combinations that may be used if a clinical trial
is not feasible, although response rates are low.
All have the potential to cause bone marrow
suppression, nausea/vomiting, alopecia, and
fatigue. Other adverse effects are specific to the
MANAGEMENT
particular agent.
» Single-agent immune checkpoint inhibitors

(nivolumab, pembrolizumab) are listed as
other treatment options for relapsed SCLC.[5]
Nivolumab, however, did not improve survival
39
Ongoing
versus chemotherapy in a randomised open-
label phase III trial of relapsed SCLC.[65]
» Nivolumab and pembrolizumab are

chemotherapy.[68][69] These immune
» The use of immune checkpoint inhibitors in

patients with disease progression while receiving
maintenance atezolizumab or durvalumab is
discouraged.[5]
» For patients with symptomatic intrathoracic

disease or with distant metastases causing
distressing symptoms, palliative radiotherapy
should be considered.

guidelines.
relapse after 6 months

Primary options
» cisplatin
-or-
» carboplatin
--AND--
» etoposide
OR
» cisplatin
-or-
» carboplatin
--AND--
» irinotecan
Secondary options
MANAGEMENT
» topotecan
OR
» lurbinectedin
Ongoing
OR
» paclitaxel
OR
» docetaxel
OR
» irinotecan
OR
» temozolomide
OR
» cyclophosphamide
-and-
» doxorubicin
-and-
» vincristine
OR
» etoposide
OR
» vinorelbine
OR
» gemcitabine
OR
» bendamustine
Tertiary options
» nivolumab
OR
» pembrolizumab
MANAGEMENT
» National Comprehensive Cancer Network

(NCCN) guidelines recommend platinum-based
regimens as subsequent systemic therapy for
patients who relapse.[5] One meta-analysis
of observational and randomised study data
found that platinum-doublet chemotherapy was
41
Ongoing
associated with a significantly higher objective
response rate and disease control rate in
patients with relapsed SCLC compared with non-
platinum-based regimens.[64]
» The original or a similar platinum-containing

regimen is recommended for patients who
remain disease-free for >6 months.[5]
» The choice between the many regimens

is complex and needs to be managed in a
specialised oncology centre.
» There are numerous chemotherapy drugs and

combinations. All have the potential to cause
bone marrow suppression, nausea/vomiting,
alopecia, and fatigue. Other adverse effects are
specific to the particular agent.
» Single-agent immune checkpoint inhibitors

(nivolumab, pembrolizumab) are listed as
other treatment options for relapsed SCLC.[5]
Nivolumab, however, did not improve survival
versus chemotherapy in a randomised open-
label phase III trial of relapsed SCLC.[65]
» Nivolumab and pembrolizumab are

chemotherapy.[68][69] These immune
» The use of immune checkpoint inhibitors in

patients with disease progression while receiving
maintenance atezolizumab or durvalumab is
discouraged.[5]
» For patients with symptomatic intrathoracic

disease or with distant metastases causing
distressing symptoms, palliative radiotherapy
should be considered.

guidelines.
MANAGEMENT
Emerging
Pembrolizumab
The KEYNOTE-604 trial investigated the use of the checkpoint inhibitor pembrolizumab or placebo, plus
etoposide and platinum chemotherapy, as first-line treatment for extensive-stage SCLC. Pembrolizumab
plus etoposide and platinum chemotherapy significantly improved progression-free survival, compared with
placebo plus etoposide and platinum chemotherapy.[70]
Adebrelimab
In patients with extensive-stage small-cell lung cancer (ES-SCLC), adebrelimab plus etoposide and
carboplatin significantly improved overall survival compared with placebo plus etoposide and carboplatin.[71]
Toripalimab
The PD-1 inhibitor toripalimab has been granted orphan drug designation for SCLC in the US. JUPITER-08
is an ongoing study that is evaluating toripalimab in combination with chemotherapy (cisplatin or carboplatin
plus etoposide), compared with placebo in combination with chemotherapy, as a first-line treatment of
extensive-stage SCLC.[72]
Serplulimab
The PD-1 inhibitor serplulimab has been granted orphan drug designation for SCLC in the US. In the
ASTRUM-005 trial, first-line treatment with serplulimab plus chemotherapy in patients with extensive-stage
SCLC resulted in improved overall survival compared with chemotherapy alone.[73]
Stereotactic radiosurgery
Stereotactic radiosurgery has superseded whole brain radiotherapy (WBRT) as the first-line treatment for
intracranial metastatic disease in most solid cancers. However, WBRT remains the first-line treatment for
intracranial metastatic disease in patients with SCLC. One meta-analysis has shown that survival outcomes
are similar following treatment with SRS, compared with WBRT, in patients with SCLC and intracranial
metastatic disease.[74]
Primary prevention
Patients should be asked about current smoking status on each presentation to medical care. Integration
of smoking cessation efforts into care should be implemented.[26] Smokers should be educated about
the health risks of smoking and advised to quit. There are multiple options (non-pharmacological and
pharmacological) that are available to assist patients with smoking cessation. One meta-analysis of
available randomised controlled trial data shows no evidence at this time that vitamin supplements decrease
lung cancer incidence or mortality.[27] In addition, the US Preventive Services Task Force (USPSTF)
recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular
disease or cancer. The USPSTF have also concluded that current evidence is insufficient to assess
the balance of benefits and harms regarding the use of multivitamin supplements for the prevention of
cardiovascular disease or cancer.[28]
Secondary prevention
MANAGEMENT
Smoking cessation should be encouraged, even in patients with cancer.[5][26] Continued smoking
among patients with SCLC has been associated with a significantly increased risk of all-cause mortality,
development of a second primary tumour, and disease recurrence.[79] In contrast, quitting smoking at the
time of diagnosis or after has been associated with a reduced risk of death.[80]
43
Small cell lung cancer Follow up
Monitoring
Monitoring
FOLLOW UP
After potentially curative treatment for lung cancer, patients should be followed regularly to assess for
disease recurrence and treatment-related toxicity. For example, following radiotherapy, patients may
develop pneumonitis. This is rarely lethal but may require treatment, and patients should be carefully
monitored with pulmonary function testing. Chemotherapy can depress blood counts, leading to anaemia
(fatigue and dyspnoea), thrombocytopenia (bleeding), and/or neutropenia (infection). Blood counts should
be monitored until patients recover. A history and physical examination should be performed every 3
to 6 months for the first 2 years or so and annually thereafter. Imaging of the chest (by chest x-ray or
computed tomography) can be performed as indicated. For patients with metastatic disease who have
completed palliative chemotherapy and/or radiotherapy, similar follow-up is recommended.
Complications
Complications Timeframe Likelihood
FOLLOW UP
post-obstructive pneumonia/hypoxia short term high
Pneumonia is common in patients with lung cancer and is often caused by a large, central obstructing
tumour. Patients may not present with classic symptoms of pneumonia such as fever, dyspnoea, and
productive cough. Chest x-ray findings can sometimes be difficult to interpret secondary to tumour-related
changes (atelectasis).
Antibiotics should be initiated. Treatment to relieve the obstruction should be instituted relatively quickly for
patients with severe pulmonary compromise.
Multiple modalities can be used, such as external beam radiotherapy, brachytherapy (temporary insertion
of a radioactive source at the site of obstruction), stent placement, laser debulking of obstructing tumour,
photodynamic therapy, and/or surgical resection. Photodynamic therapy is a minimally invasive modality
that involves the interaction of light, a photosensitising agent, and oxygen. Briefly, the photosensitising
agent is administered intravenously and is absorbed by cells throughout the body. Then a laser beam at a
predetermined wavelength is focused via a flexible fibre bronchoscope on the endobronchial tumour. The
photosensitising agent absorbs photons of the appropriate wavelength, creating reactive oxygen species
that are toxic to cancer cells.
chemotherapy-induced haematological toxicity short term high
Chemotherapy commonly causes haematological toxicity (e.g., anaemia, neutropenia, thrombocytopenia),

which may lead to infection requiring antibiotics, bleeding, hospitalisation, or the need for supportive care
including blood transfusions.
While granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating

factor (GM-CSF) is not recommended for use during concurrent chemotherapy and radiation for
limited-stage SCLC, either G-CSF or trilaciclib may be used to minimise risk of chemotherapy-induced
myelosuppression for extensive-stage SCLC.[5]
superior vena cava syndrome (SVCS) short term medium
The most common cause of SVCS is lung cancer. Bulky mediastinal adenopathy or medial extension of
a right upper lobe tumour can compress the superior vena cava (SVC), impeding the return of blood from
the face and arms to the heart. Numerous collateral pathways develop when the SVC is compressed.
The acuity and severity of symptoms depend on the speed of obstruction. The syndrome is characterised
by facial and upper extremity oedema, dyspnoea, cough, and orthopnoea. Physical examination
demonstrates facial plethora and distended neck, chest wall, and occasionally abdominal wall veins.[76]
SVCS is rarely a medical emergency and every effort should be made to obtain a diagnosis before
initiating therapy. Supplemental oxygen and head elevation are often helpful. Treatment depends on the
clinical scenario and stage of disease. Patients with marked symptoms should have treatment initiated
relatively quickly. Most patients will improve with radiotherapy and/or chemotherapy, but the response
may take several days. Endovascular stents may be effective with more rapid symptomatic relief. Surgical
intervention is rarely required.[76]
45

paraneoplastic syndromes short term medium
FOLLOW UP
Treatment of the underlying tumour often alleviates symptoms from endocrine-mediated

paraneoplastic syndromes (e.g., syndrome of inappropriate secretion of antidiuretic hormone, ectopic
adrenocorticotrophic hormone production). Neurological paraneoplastic syndromes are more variable in
responding to treatment of the underlying tumour. Other supportive measures depend on the underlying
syndrome.
radiation-induced oesophageal injury variable high
Oesophagitis is a common adverse effect of radiotherapy. Symptoms typically develop 3 to 4 weeks after
starting radiotherapy, peak towards the completion of treatment, and often persist for several weeks after
radiotherapy. Pre-existing gastro-oesophageal reflux may exacerbate symptoms and should be treated.
Severe acute oesophagitis occurs in 15% to 25% of patients undergoing concurrent chemoradiotherapy.
Rarely, patients may require hospitalisation, endoscopy, or placement of a percutaneous endoscopic
gastrostomy tube.
Late injury is less common, but may manifest itself between about 3 and 8 months after completion of
radiotherapy as an oesophageal stricture with dysphagia. Treatment may involve periodic dilation. Death
related to tracheo-oesophageal fistula or oesophageal perforation has been reported in up to 1% of
patients.[77]
immune check point inhibitor-related toxicity variable medium
Immune checkpoint inhibitors can cause unique immune-mediated adverse events that are not seen with
traditional cytotoxic chemotherapy, such as pneumonitis, colitis, dermatitis, myositis, and hypothyroidism,
among others. In general, treatment includes corticosteroids and may require discontinuation of
immunotherapy treatment in the case of high-grade toxicities or some neurological, haematological, and
cardiac toxicities. Grade 3 or higher toxicities generally warrant high-dose corticosteroids tapered over
4 to 6 weeks, and additional immunosuppressive therapies (such as infliximab) may need to be used
in some cases. For endocrinopathies controlled by hormone replacement, immune checkpoint inhibitor
therapy may be continued even for high-grade toxicity. Consultation of guidelines for detailed organ-
specific treatment recommendations is warranted.[54] [55]
radiation-induced lung injury variable medium
Radiation-induced lung injury is believed to result from inflammation and chronic oxidative stress, resulting
in diffuse alveolar damage. The likelihood of injury depends on the dose and volume of irradiated lung.
Acute radiation pneumonitis may manifest 1 to 6 months after radiotherapy as shortness of breath, dry
cough, and occasionally fever. Chest auscultation is typically unremarkable, although friction rub or rales
are possible. Chest x-ray should be obtained but is often unrevealing. Radiation pneumonitis is a clinical
diagnosis, made after excluding disorders that cause similar symptoms.
Primary treatment for symptomatic acute pneumonitis is oral corticosteroids. We recommend oral
prednisolone, 40 to 60 mg once daily for 1 to 2 weeks followed by a slow taper (reducing by about 10 mg
every 1-2 weeks). The majority of patients with acute pneumonitis recover, and progressive symptoms
requiring oxygen or hospitalisation are uncommon.
Most patients who receive thoracic radiotherapy develop chronic opacities on imaging, often attributed
to fibrosis. The majority of such patients are asymptomatic and do not require treatment. However,

symptomatic pulmonary fibrosis can be chronic and debilitating, particularly in patients with poor baseline
pulmonary reserve. Established radiation fibrosis is generally irreversible.[78]
FOLLOW UP
acute/massive haemoptysis variable low
Patients may present with acute or worsening haemoptysis in the setting of airway invasion or proximity of
a tumour to an airway. Haemoptysis of more than 1 tablespoon should be a cause for urgent action, with
further investigation of the source of bleeding (i.e., bronchoscopy) and consideration of palliative radiation
if indicated. Prophylactic radiation is not specifically used for this purpose as it is hard to anticipate whether
and/or when it may happen, even in the setting of endobronchial lesions.
Prognosis
Survival
Survival after definitive treatment of SCLC is dependent on stage. The 5-year survival rates are
approximately 30% to 35% for limited stage and 1% to 5% for extensive stage.[47] [51] Treatment patterns
and short survival outcomes for SCLC have remained constant from the year 2000 to 2020. However, this
may change after the adoption of immuno-oncology therapies for SCLC.[75]
47
Small cell lung cancer Guidelines
Diagnostic guidelines
United Kingdom
Lung cancer: diagnosis and management (ht tps://www.nice.org.uk/guidance/

ng122)
Published by: National Institute for Health and Care Excellence Last published: 2023
Suspected cancer: recognition and referral (ht tps://www.nice.org.uk/

guidance/ng12)
Management of lung cancer (ht tps://www.sign.ac.uk/our-guidelines)

Published by: Scottish Intercollegiate Guidelines Network Last published: 2014
GUIDELINES
Europe
EANO-ESMO clinical practice guidelines for diagnosis, treatment and

follow-up of patients with brain metastasis from solid tumours (ht tps://
www.esmo.org/guidelines/guidelines-by-topic/neuro-oncology)
Published by: European Association of Neuro-Oncology; European Last published: 2021
Society for Medical Oncology
North America
ACR appropriateness criteria: noninvasive clinical staging of primary lung

cancer (ht tps://www.acr.org/Quality-Safety/Appropriateness-Criteria)
Published by: American College of Radiology Last published: 2018
NCCN clinical practice guidelines in oncology: small cell lung cancer

(ht tps://www.nccn.org/professionals/physician_gls/default.aspx)
Published by: National Comprehensive Cancer Network Last published: 2023
Establishing the diagnosis of lung cancer: diagnosis and management of

lung cancer, 3rd ed (ht tps://www.chestnet.org/guidelines/thoracic-oncology)
Published by: American College of Chest Physicians Last published: 2013
Treatment guidelines
United Kingdom
Lung cancer: diagnosis and management (ht tps://www.nice.org.uk/guidance/

ng122)
Management of lung cancer (ht tps://www.sign.ac.uk/our-guidelines)

Published by: Scottish Intercollegiate Guidelines Network Last published: 2014
Europe
Small-cell lung cancer: ESMO clinical practice guidelines for diagnosis,

treatment and follow-up (ht tps://www.esmo.org/guidelines/lung-and-chest-
GUIDELINES
tumours)
Published by: European Society for Medical Oncology Last published: 2021
EANO-ESMO clinical practice guidelines for diagnosis, treatment and

follow-up of patients with brain metastasis from solid tumours (ht tps://
www.esmo.org/guidelines/guidelines-by-topic/neuro-oncology)
Published by: European Association of Neuro-Oncology; European Last published: 2021
Society for Medical Oncology
49
North America
Guidelines and advice: lung cancer (ht tps://www.cancercareontario.ca/en/

guidelines-advice/types-of-cancer/lung?f%5B0%5D=field_type_of_cancer
%3A511)
Published by: Cancer Care Ontario Last published: 2022
NCCN clinical practice guidelines in oncology: small cell lung cancer

(ht tps://www.nccn.org/professionals/physician_gls/default.aspx)
Published by: National Comprehensive Cancer Network Last published: 2023
National Cancer Institute small cell lung cancer treatment (PDQ®) – health
professional (ht tps://www.cancer.gov/types/lung/hp)
Published by: National Cancer Institute Last published: 2022
Radiation therapy for small cell lung cancer: an ASTRO clinical practice
GUIDELINES
guideline (ht tps://www.astro.org/Patient-Care-and-Research/Clinical-Practice-

Statements/Clinical-Practice-Guidelines)
Published by: American Society for Radiation Oncology Last published: 2020
Treatment of small cell lung cancer: diagnosis and management of lung

cancer, 3rd ed (ht tps://www.chestnet.org/guidelines/thoracic-oncology)
Published by: American College of Chest Physicians Last published: 2013
Small cell lung cancer References
Key articles
• Simone CB 2nd, Bogart JA, Cabrera AR, et al. Radiation therapy for small cell lung cancer:
REFERENCES
an ASTRO clinical practice guideline. Pract Radiat Oncol. 2020 May - Jun;10(3):158-73. Full
text (https://www.practicalradonc.org/article/S1879-8500(20)30053-9/fulltext) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/32222430?tool=bestpractice.bmj.com)
References
1. Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of
lung tumours. Eur Respir J. 2001 Dec;18(6):1059-68. Full text (https://erj.ersjournals.com/
content/18/6/1059.long) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/11829087?
tool=bestpractice.bmj.com)
2. WHO Classification of Tumours Editorial Board. World Health Organization classification of tumours:
thoracic tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2021.
3. US Public Health Service. Smoking and health. Report of the Advisory Committee to the Surgeon
General of the Public Health Service. PHS Publication no. 1103. Washington, DC: US Government
Printing Office; 1964.
4. Beckles MA, Spiro SG, Colice GL, et al. Initial evaluation of the patient with lung cancer: symptoms,
signs, laboratory tests, and paraneoplastic syndromes. Chest. 2003 Jan;123(1 suppl):97S-104S.
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12527569?tool=bestpractice.bmj.com)
5. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: small cell
lung cancer [internet publication]. Full text (https://www.nccn.org/guidelines/category_1)
6. American Cancer Society. Cancer facts & figures 2015. 2015 [internet publication]. Full text (http://
www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/index)
7. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer stat facts:
lung and bronchus cancer [internet publication]. Full text (https://seer.cancer.gov/statfacts/html/
lungb.html)
8. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33.
Full text (https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21654) Abstract (http://
9. GBD 2019 Respiratory Tract Cancers Collaborators. Global, regional, and national burden of
respiratory tract cancers and associated risk factors from 1990 to 2019: a systematic analysis for
the Global Burden of Disease Study 2019. Lancet Respir Med. 2021 Sep;9(9):1030-49. Full text
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410610) Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/34411511?tool=bestpractice.bmj.com)
51
10. American Cancer Society. What is lung cancer? Oct 2019 [internet publication]. Full text (https://
www.cancer.org/cancer/lung-cancer/about/what-is.html)
REFERENCES
11. Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003 Jan;123(1 suppl):21S-49S. Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/12527563?tool=bestpractice.bmj.com)
12. American Cancer Society. Lung cancer risk factors. Oct 2019 [internet publication]. Full text (https://
www.cancer.org/cancer/lung-cancer/causes-risks-prevention/risk-factors.html)
13. Doll R, Hill D. Smoking and carcinoma of the lung; a preliminary report. BMJ. 1950
Sep 30;2(4682):739-48. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14772469?
14. Levin ML, Goldstein H, Gerhardt PR. Cancer and tobacco smoking; a preliminary report.
JAMA. 1950 May 27;143(4):336-8. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15415261?
15. Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma;
a study of six hundred and eighty-four proved cases. JAMA. 1950 May 27;143(4):329-36. Abstract
16. Warren GW, Alberg AJ, Kraft AS, et al. The 2014 Surgeon General's report: "The health
consequences of smoking – 50 years of progress": a paradigm shift in cancer care. Cancer. 2014 Jul
1;120(13):1914-6. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928784) Abstract (http://
17. Eidy M, Tishkowski K. Radon toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2022. Full text (https://www.ncbi.nlm.nih.gov/books/NBK562321) Abstract (http://
18. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer
in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end
results database. J Clin Oncol. 2006 Oct 1;24(28):4539-44. Full text (https://ascopubs.org/
doi/10.1200/JCO.2005.04.4859) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17008692?
19. Park HY, Kang D, Shin SH, et al. Chronic obstructive pulmonary disease and lung cancer
incidence in never smokers: a cohort study. Thorax. 2020 Jun;75(6):506-9. Full text (https://
thorax.bmj.com/content/75/6/506.long) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/32241883?
20. Kerpel-Fronius A, Tammemägi M, Cavic M, et al. Screening for lung cancer in individuals who
never smoked: an International Association for the Study of Lung Cancer Early Detection and
Screening Committee report. J Thorac Oncol. 2022 Jan;17(1):56-66. Full text (https://www.jto.org/
article/S1556-0864(21)02391-1/fulltext) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/34455065?
21. Abdel-Rahman O. Incidence and mortality of lung cancer among never smokers in relationship
to secondhand smoking: findings from the PLCO trial. Clin Lung Cancer. 2020 Sep;21(5):415-20.
REFERENCES
22. Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: collaborative analysis
of individual data from 13 European case-control studies. BMJ. 2005 Jan 29;330(7485):223. Full
text (https://www.bmj.com/content/330/7485/223.long) Abstract (http://www.ncbi.nlm.nih.gov/
23. Zielinski JM, Carr Z, Krewski D, et al. World Health Organization's International Radon Project.
J Toxicol Environ Health A. 2006 Apr;69(7):759-69. Abstract (http://www.ncbi.nlm.nih.gov/
24. Nielsen LS, Bælum J, Rasmussen J, et al. Occupational asbestos exposure and lung cancer: a
systematic review of the literature. Arch Environ Occup Health. 2014;69(4):191-206. Abstract (http://
25. Hessel PA, Gamble JF, McDonald JC. Asbestos, asbestosis, and lung cancer: a critical assessment of
the epidemiological evidence. Thorax. 2005 May;60(5):433-6. Abstract (http://www.ncbi.nlm.nih.gov/
26. Leone FT, Evers-Casey S, Toll BA, et al. Treatment of tobacco use in lung cancer: diagnosis and
management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical
practice guidelines. Chest. 2013 May;143(5 Suppl):e61S-77S. Full text (https://journal.chestnet.org/
27. Cortés-Jofré M, Rueda JR, Asenjo-Lobos C, et al. Drugs for preventing lung cancer in healthy people.
Cochrane Database Syst Rev. 2020 Mar 4;(3):CD002141. Full text (https://www.cochranelibrary.com/
cdsr/doi/10.1002/14651858.CD002141.pub3/full) Abstract (http://www.ncbi.nlm.nih.gov/
28. US Preventive Services Task Force; Mangione CM, Barry MJ, et al. Vitamin, mineral, and multivitamin
supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force
recommendation statement. JAMA. 2022 Jun 21;327(23):2326-33. Full text (https://jamanetwork.com/
journals/jama/fullarticle/2793446) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/35727271?
29. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012 Feb;14(1):48-54.
30. Miller KL, Shafman TD, Marks LB. A practical approach to pulmonary risk assessment in the
radiotherapy of lung cancer. Semin Radiat Oncol. 2004 Oct;14(4):298-307. Abstract (http://
31. Beckles MA, Spiro SG, Colice GL, et al. The physiologic evaluation of patients with lung cancer
being considered for resectional surgery. Chest. 2003 Jan;123(1 suppl):105S-14S. Abstract (http://
53
32. Arends J, Strasser F, Gonella S, et al. Cancer cachexia in adult patients: ESMO clinical practice
guidelines. ESMO Open. 2021 Jun;6(3):100092. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC8233663) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/34144781?tool=bestpractice.bmj.com)
REFERENCES
33. Pastis NJ, Silvestri GA. Tissue procurement: bronchoscopic techniques. In: Pass HI, Carbone DP,
Johnson DE, et al., eds. Lung cancer - principles and practice. 3rd ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2005:358-71.
34. Steinfort DP, Khor YH, Manser RL, et al. Radial probe endobronchial ultrasound for the diagnosis of
peripheral lung cancer: systematic review and meta-analysis. Eur Respir J. 2011 Apr;37(4):902-10.
Full text (https://erj.ersjournals.com/content/37/4/902.long) Abstract (http://www.ncbi.nlm.nih.gov/
35. Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer: Veterans Administration Lung Study
Group versus International Association for the Study of Lung Cancer--what limits limited disease?
Lung Cancer. 2002 Sep;37(3):271-6. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12234695?
36. Kalemkerian GP, Gadgeel SM. Modern staging of small cell lung cancer. J Natl Compr Canc Netw.
2013 Jan 1;11(1):99-104. Full text (https://jnccn.org/view/journals/jnccn/11/1/article-p99.xml)
37. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer;
2017.
38. American College of Radiology. ACR Appropriateness Criteria® lung cancer screening. 2022 [internet
publication]. Full text (https://acsearch.acr.org/docs/3102390/Narrative)
39. US Preventive Services Task Force; Krist AH, Davidson KW, Mangione CM, et al. Screening for
lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021 Mar
9;325(10):962-70. Full text (https://jamanetwork.com/journals/jama/fullarticle/2777244) Abstract
40. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: lung cancer
screening [internet publication]. Full text (https://www.nccn.org/guidelines/category_2)
41. Aberle DR, Adams AM, Berg CD, et al; National Lung Screening Trial Research Team. Reduced
lung cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug
4;365(5):395-409. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356534) Abstract (http://
42. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with
volume CT screening in a randomized trial. N Engl J Med. 2020 Feb 6;382(6):503-13. Full text
(https://www.nejm.org/doi/10.1056/NEJMoa1911793) Abstract (http://www.ncbi.nlm.nih.gov/
43. Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-
cell lung cancer. N Engl J Med. 1992 Dec 3;327(23):1618-24. Full text (https://www.nejm.org/
doi/10.1056/NEJM199212033272302) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/1331787?
REFERENCES
44. Simone CB 2nd, Bogart JA, Cabrera AR, et al. Radiation therapy for small cell lung cancer:
an ASTRO clinical practice guideline. Pract Radiat Oncol. 2020 May - Jun;10(3):158-73. Full
text (https://www.practicalradonc.org/article/S1879-8500(20)30053-9/fulltext) Abstract (http://
45. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic
radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin
Oncol. 2004 Dec 1;22(23):4837-45 Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15570087?
46. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy
in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med.
1999 Jan 28;340(4):265-71. Full text (https://www.nejm.org/doi/10.1056/NEJM199901283400403)
47. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy
in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised,
superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-25. Full text (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC5555437) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/28642008?
48. Bogart J, Wang X, Masters G, et al. High-dose once-daily thoracic radiotherapy in limited-stage small-
cell lung cancer: CALGB 30610 (Alliance)/RTOG 0538. J Clin Oncol. 2023 May 1;41(13):2394-402.
49. Li D, Deng C, Zheng Q, et al. Impact of adjuvant therapy on survival in surgically resected
limited-stage small cell lung cancer. Front Oncol. 2021 Sep 23;11:704517. Full text (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC8495161) Abstract (http://www.ncbi.nlm.nih.gov/
50. Ligibel JA, Bohlke K, May AM, et al. Exercise, diet, and weight management during cancer treatment:
ASCO guideline. J Clin Oncol. 2022 Aug 1;40(22):2491-507. Full text (https://ascopubs.org/
doi/10.1200/JC0.22.00687?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub
%20%200pubmed) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/35576506?
51. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage
small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-9. Full text (https://www.nejm.org/
doi/10.1056/NEJMoa1809064) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30280641?
52. Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-
etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell
lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial.
55
Lancet Oncol. 2021 Jan;22(1):51-65. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/33285097?
REFERENCES
53. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-
etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised,
controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-39. Abstract (http://
54. Beavers CJ, Rodgers JE, Bagnola AJ, et al. Cardio-oncology drug interactions: a scientific
statement from the American Heart Association. Circulation. 2022 Apr 12;145(15):e811-38.
Full text (https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001056?rfr_dat=cr_pub
++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org) Abstract (http://
55. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events
in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin
Oncol. 2021 Dec 20;39(36):4073-126. Full text (https://ascopubs.org/doi/10.1200/JCO.21.01440?
url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) Abstract (http://
56. Owonikoko TK, Park K, Govindan R, et al. Nivolumab and ipilimumab as maintenance therapy in
extensive-disease small-cell lung cancer: CheckMate 451. J Clin Oncol. 2021 Apr 20;39(12):1349-59.
Full text (https://ascopubs.org/doi/10.1200/JCO.20.02212) Abstract (http://www.ncbi.nlm.nih.gov/
57. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment
of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol. 1999
Jul;17(7):2092-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10561263?tool=bestpractice.bmj.com)
58. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-
cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3;385(9962):36-42. Full text
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61085-0/fulltext) Abstract (http://
59. Seto T, Takahashi T, Yamanaka T, et al. Prophylactic cranial irradiation (PCI) has a detrimental effect
on the overall survival (OS) of patients (pts) with extensive disease small cell lung cancer (ED-
SCLC): results of a Japanese randomized phase III trial. 2014 ASCO Annual Meeting Abstracts.
J Clin Oncol. 2014 May 20;32(15 suppl):7503. Full text (https://ascopubs.org/doi/10.1200/
jco.2014.32.15_suppl.7503)
60. Le Rhun E, Guckenberger M, Smits M, et al. EANO-ESMO clinical practice guidelines for diagnosis,
treatment and follow-up of patients with brain metastasis from solid tumours. Ann Oncol. 2021
Nov;32(11):1332-47. Full text (https://www.annalsofoncology.org/article/S0923-7534(21)02214-6/
fulltext) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/34364998?tool=bestpractice.bmj.com)
61. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-
cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. Full text (https://www.nejm.org/
doi/10.1056/NEJMoa071780) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17699816?
REFERENCES
62. Le Péchoux C, Dunant A, Senan S, et al; Prophylactic Cranial Irradiation (PCI) Collaborative Group.
Standard-dose versus higher-dose prophylactic cranial irradiation in patients with limited-stage
small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy: a
randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Abstract (http://www.ncbi.nlm.nih.gov/
63. Le Péchoux C, Laplanche A, Faivre-Finn C, et al; Prophylactic Cranial Irradiation (PCI) Collaborative
Group. Clinical neurological outcome and quality of life among patients with limited small-
cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup
phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol. 2011
May;22(5):1154-63. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082159) Abstract
64. Horiuchi K, Sato T, Kuno T, et al. Platinum-doublet chemotherapy as second-line treatment

for relapsed patients with small-cell lung cancer: A systematic review and meta-analysis.
Lung Cancer. 2021 Jun;156:59-67. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/33894495?
65. Spigel DR, Vicente D, Ciuleanu TE, et al. Second-line nivolumab in relapsed small-cell lung cancer:
CheckMate 331. Ann Oncol. 2021 May;32(5):631-41. Full text (https://www.annalsofoncology.org/
66. Miller KL, Shafman TD, Anscher MS, et al. Bronchial stenosis: an underreported complication of high-
dose external beam radiotherapy for lung cancer? Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):64-9.
67. Socinski MA, Morris DE, Halle JS, et al. Induction and concurrent chemotherapy with high-
dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung
cancer: a dose-escalation phase I trial. J Clin Oncol. 2004 Nov 1;22(21):4341-50. Abstract (http://
68. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab
in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial.
Lancet Oncol. 2016 Jul;17(7):883-95. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27269741?
69. Horn L, Reck M, Spigel DR. The future of immunotherapy in the treatment of small cell lung
cancer. Oncologist. 2016 Aug;21(8):910-21. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
70. Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum
as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind,
Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-79. Full text (https://
57
www.ncbi.nlm.nih.gov/pmc/articles/PMC7474472) Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
71. Wang J, Zhou C, Yao W, et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line
treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised,
double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-47. Abstract (http://
72. US National Library of Medicine. ClinicalTrials.gov. Toripalimab in combination with platinum plus
etoposidein patients with extensive-stage small cell lung cancer. Sep 2020 [internet publication]. Full
text (https://clinicaltrials.gov/ct2/show/NCT04012606)
73. Cheng Y, Han L, Wu L, et al. Effect of first-line derplulimab vs placebo added to chemotherapy on
survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical
trial. JAMA. 2022 Sep 27;328(12):1223-32. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/36166026?
74. Gaebe K, Li AY, Park A, et al. Stereotactic radiosurgery versus whole brain radiotherapy in patients
with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis.
Lancet Oncol. 2022 Jul;23(7):931-39. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/35644163?
75. Johal S, Hettle R, Carroll J, et al. Real-world treatment patterns and outcomes in small-cell
lung cancer: a systematic literature review. J Thorac Dis. 2021 Jun;13(6):3692-707. Full text
76. Straka C, Ying J, Kong FM, et al. Review of evolving etiologies, implications and treatment
strategies for the superior vena cava syndrome. Springerplus. 2016 Feb 29;5:229. Full text
77. Werner-Wasik M, Yorke E, Deasy J, et al. Radiation dose-volume effects in the esophagus. Int J
Radiat Biol Phys. 2010 Mar 1;76(3 Suppl):S86-93. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
78. Ghafoori P, Kelsey CR, Marks LB, et al. Radiation-induced lung injury. Assessment, management, and
prevention. Oncology. 2008 Jan;22(1):37-47. Full text (https://www.cancernetwork.com/view/radiation-
induced-lung-injury-assessment-management-and-prevention) Abstract (http://www.ncbi.nlm.nih.gov/
79. Parsons A, Daley A, Begh R, et al. Influence of smoking cessation after diagnosis of early stage
lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010
Jan 21;340:b5569. Full text (https://www.bmj.com/content/340/bmj.b5569.long) Abstract (http://
80. Chen J, Jiang R, Garces YI, et al. Prognostic factors for limited-stage small cell lung cancer: a study of
284 patients. Lung Cancer. 2010 Feb;67(2):221-6. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
REFERENCES
59
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Contributors:
// Authors:
Catherine B. Meador, MD, PhD

Attending Physician
Center for Thoracic Cancers, Instructor in Medicine, Harvard Medical School, Massachusetts General
Hospital, Boston, MA
DISCLOSURES: CBM declares that she has no competing interests.
// Acknowledgements:
Dr Catherine B. Meador would like to gratefully acknowledge Dr Leena Gandhi, Dr Alvin R. Cabrera, Dr
Christopher R. Kelsey, Dr Lawrence B. Marks, and Dr Rebecca Suk Heist, previous contributors to this
topic.
DISCLOSURES: LG, ARC, CRK, and LBM declare that they have no competing interests. RSH has
received honouraria for consulting from Novartis, Abbvie, Daichii Sankyo, and EMD Serono. RSH's
institution (not RSH) has received research funding from Agios, Abbvie, Exelixis, Daichii Sankyo, Novartis,
Lilly, Mirati, Corvus, Incyte, and Genentech Roche.
// Peer Reviewers:
Alan Neville, MD
Professor
Assistant Dean, Undergraduate Program, McMaster University, Hamilton, Ontario, Canada
DISCLOSURES: AN declares that he has no competing interests.

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Small cell lung cancer

Straight to the point of care

Last updated: Jun 13, 2023

• Squamous cell papilloma, not otherwise specified (NOS)

• Atypical adenomatous hyperplasia

• Adenocarcinoma in situ, non-mucinous

• Minimally invasive adenocarcinoma

• Minimally invasive adenocarcinoma, non-mucinous

• Mixed invasive mucinous and non-mucinous adenocarcinoma

• Squamous cell carcinoma in situ

• Moderate squamous dysplasia

• Squamous cell carcinoma, NOS

• Squamous cell carcinoma, keratinising

• Large cell carcinoma

• Giant cell carcinoma

• Diffuse idiopathic neuroendocrine cell hyperplasia

• Carcinoid tumour, NOS/neuroendocrine tumour, NOS

• Small cell carcinoma

• Combined small cell carcinoma

• Combined large cell neuroendocrine carcinoma

Tumours of ectopic tissues

• Lymphomatoid granulomatosis, grade 1

SCLC is associated with paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome,

• Bronchoscopy is performed when CT abnormalities (i.e., a mass or adenopathy) are

History and exam

chest pain (common)

weight loss (common)

Other diagnostic factors

pulmonary examination abnormalities (common)

personality changes (uncommon)

nausea and vomiting (uncommon)

bone pain and/or fractures (uncommon)

cervical or supraclavicular adenopathy (uncommon)

facial swelling (uncommon)

dilated neck or chest/abdominal wall veins (uncommon)

hypertrophic osteoarthropathy (uncommon)

environmental tobacco exposure

radon gas exposure

CT chest, liver, and adrenal glands massive

Other tests to consider

bone scan skeletal metastases

• Baseline assessment is recommended before initiation of treatment.

Condition Differentiating signs / Differentiating tests

Pneumonia/bronchitis • Typical symptoms include • CXR is the first test

Carcinoid tumour • Often asymptomatic with • CT chest: 80% of carcinoid

Condition Differentiating signs / Differentiating tests

(TTNA) can reveal

Infectious granuloma • History may include travel • CT-guided transthoracic

Condition Differentiating signs / Differentiating tests

Sarcoidosis • Cough, dyspnoea, fatigue, • CT chest: mediastinal

Condition Differentiating signs / Differentiating tests

Rheumatoid arthritis • Arthralgias, pain, skin • CT chest typically shows

pleuritis, joint pain, and predominantly in peripheral

Condition Differentiating signs / Differentiating tests

Granulomatosis with • Cough, chest pain, • CT chest shows solitary

Hamartoma • Usually asymptomatic • CT chest shows well-

Condition Differentiating signs / Differentiating tests

Amyloidosis • Weight loss, paraesthesias, • CT chest shows lung

common. Small vessel monoclonal protein; seen

Bronchiolitis obliterans • Normally presents as a flu- • CT chest is preferable to

Condition Differentiating signs / Differentiating tests

Condition Differentiating signs / Differentiating tests

Condition Differentiating signs / Differentiating tests