Lung cancer: clinical review

The diagnosis and management of lung cancer, including risk factors and indications for an urgent chest X-ray.

Frontal chest X-ray of the lungs of an 83-year-old patient with small cell lung cancer (Photograph: SPL)
Frontal chest X-ray of the lungs of an 83-year-old patient with small cell lung cancer (Photograph: SPL)

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base

Section 1: Epidemiology and aetiology

In the UK, the incidence of lung cancer is high; in 2013, approximately 45,500 patients were diagnosed with lung cancer and in 2014 about 35,900 people died from the disease. These figures are higher than those reported in 2008.

In men, lung cancer is the second most common cancer after prostate cancer and accounts for 14% of all male cancers. Lung cancer accounts for 12% of all female cancers and is now ranked second after breast cancer; having recently become more common than colorectal cancer.

While not the most common cancer, the mortality associated with lung cancer remains the highest, accounting for 22% of cancer deaths in 2014. Lung cancer is rarely diagnosed in people under the age of 40 years and incidence peaks at the age of 80-84 years.

Risk factors

It is estimated that 90% of male and 83% of female lung cancers are caused by smoking. Current smokers are 15 times more likely to die from lung cancer than lifelong non-smokers.

The duration of smoking affects the risk of developing lung cancer. A lifelong male smoker has a cumulative risk of 15.9% of developing lung cancer by the age of 75 years. For men who stop smoking at age 60, 50, 40 and 30 years, the cumulative risk of dying from lung cancer falls to 9.9%, 6.0%, 3.0% and 1.7% respectively.1 Similar health benefits of sustained and early smoking cessation have been documented for women.

Over the past decade there has been much interest in the risk associated with passive exposure. Meta-analyses have shown that passive smoking increases the risk of developing lung cancer by 25%.

Other risk factors associated with lung cancer include a previous diagnosis of lung cancer, radon gas, industrial exposure, air pollution, a positive family history, HIV and AIDS.

Lung cancer
Smokers are 15 times more likely to die from lung cancer than non-smokers.


Lung cancer is traditionally subclassified into two groups, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). SCLC accounts for around 12% of all lung cancers. The main types of NSCLC are squamous cell, adenocarcinoma and large cell cancers, which account for 42%, 39% and 8% of all UK NSCLC cases respectively.

All types of lung cancer are linked to smoking, however adenocarcinoma is the most common histological type in non-smokers.

Around 80 per cent of patients will have advanced disease at the time of diagnosis, so palliative treatments will form the mainstay of therapy in most patients. Treatment modalities include surgery, chemotherapy, radiotherapy, palliative and symptom-based care.

Although survival rates from lung cancer have increased over the past 10 years, the prognosis remains poor and lung cancer is the most common cause of cancer-related death worldwide. The median survival from the time of diagnosis in England is 203 days.

Important Around 90% of male and 83% of female lung cancers are caused by smoking.

Section 2: Making the diagnosis

Patients with lung cancer can present with many symptoms related to the primary tumour, extrathoracic spread, paraneoplastic syndromes or constitutional effects.

The most common symptoms include coughdyspnoeaweight loss and chest painHaemoptysis and bone pain are also relatively common. The current NICE guideline advises an urgent chest X-ray in a number of settings (see box below).

Lung cancer
Common symptoms include cough, dyspnoea, and chest pain.

The patient should be referred under the two-week wait rule if the chest X-ray is abnormal. Immediate referral is warranted when the presentation is of persistent or unexplained haemoptysis in a smoker or ex-smoker aged over 40 years, or if there are signs of superior vena caval obstruction and stridor.

As it stands, 34% of lung cancer is diagnosed as a result of an emergency presentation; invariably at a later stage with poor outcomes.

All patients with suspected lung cancer should have a complete history and physical examination, haematology and biochemistry analysis and contrast-enhanced CT of the chest, liver and adrenals.

The main purpose of these investigations is to document comorbidities and performance status (PS), and radiologically diagnose and stage the malignancy. The PS determines the patient's general well-being. Patients are usually fit for active treatment if the PS is less than two. The score aims to quantify a patient's fitness for day-to-day activities, so general practice is a good setting for this.

In cases of poor PS, significant comorbidities, patient preference, or where further investigation is contraindicated or inappropriate, a radiological diagnosis may be acceptable. In patients where treatment is indicated, radiological diagnosis is insufficient and histological confirmation of malignancy will be necessary.

The goal of these initial investigations is to choose a site for biopsy that will provide the most clinical information on diagnosis and staging, with the least risk to the patient.

Tissue can be obtained by different techniques based on findings from radiological investigations. The sampling target should be the lesion that will establish the highest disease stage, assuming it is not inaccessible and the sampling procedure does not pose a particularly high risk to the patient (for example, brain metastasis).


Immediate chest X-ray

  • Haemoptysis

Chest X-ray (If symptoms are unexplained and persisting for more than three weeks)

  • Cough
  • Weight loss
  • Chest/shoulder pain
  • Dyspnoea
  • Hoarseness
  • Chest signs
  • Finger clubbing
  • Cervical/supraclavicular lymphadenopathy
  • Thrombocytosis
  • Signs suggestive of metastatic disease

Adapted from NICE guideline CG121

Invasive investigations

Lung cancer
Refer patients under the two-week wait rule if chest X-ray is abnormal.

Invasive investigations can include sampling of supraclavicular lymph nodes, aspiration of pleural effusion, bronchoscopy and associated techniques, such as biopsy, brushings, washings, blind transbronchial needle aspiration (TBNA), endobronchial ultrasound (EBUS) guided TBNA, CT guided transthoracic needle aspiration, oesophageal ultrasound guided aspiration, mediastinoscopy and thoracotomy.

EBUS has now become the first-line investigation of choice for diagnosing and staging presumed lung cancer with associated mediastinal adenopathy or central tumours. A randomised controlled study, published in 2015, showed a significantly reduced time from investigation to treatment decision versus conventional flexible bronchoscopy.3

For example, a patient whose chest CT reveals a left upper lobe mass with right paratracheal lymph node enlargement should have the lymph nodes sampled. This can confirm malignancy and establish the stage of disease, whereas sampling the mass can only confirm NSCLCand an additional procedure would be required to complete the staging.

NSCLC is staged according to the tumour, node, metastasis (TNM) classification, whereas SCLC is staged as limited or extensive disease.

Important Endobronchial ultrasound is the first-line investigation for diagnosing and staging presumed lung cancer with associated mediastinal adenopathy or central tumours.

Section 3: Managing the condition

All patients with suspected lung cancer should be referred to a chest physician under the two-week wait rule. Patients should have access to a clinical nurse specialist at all stages of care and should be offered general and specific palliative care according to their needs.

Cases of confirmed malignancy should be discussed at a multidisciplinary team meeting consisting of a chest physician, thoracic surgeon, medical and radiation oncologist, radiologist and histopathologist.


In cases where active treatment is indicated, for example in patients with adequate PS and without significant comorbidities, the choice of treatment is based on tumour histology and disease stage. The stage will also dictate whether the treatment is radical or palliative.

Management of NSCLC

For NSCLC, radical treatment should be offered for early stage disease, either by surgery or radiotherapy. More advanced stage confirmed after initial surgical resection may benefit from adjuvant chemotherapy, depending on the final pathological stage.

The NICE guidelines advise open or thoracoscopic lobectomy as the first choice surgical treatment.

More advanced surgery, including bilobectomy, pneumonectomy, sleeve resections (resections aiming to preserve functioning lung) and chest wall resections should be offered if clear resection margins can be obtained. Anatomical resection (segmentectomy) can be offered to patients with poor PS or patients whose lung function would preclude lobectomy / pneumonectomy, provided the disease is localised.

An alternative treatment approach to surgery is radiotherapy, which can be offered to patients who are unsuitable for surgery. Stereotactic radiotherapy, as opposed to standard external beam radiotherapy, uses focused beams of radiotherapy in fewer treatment fractions to more accurately target the tumour. There appear to be fewer side effects and it is increasingly being used for radical management of NSCLC in patients unfit for surgical resection.

In more advanced disease, combined chemoradiotherapy may be appropriate. The chemotherapeutic agents available are different depending on the subtype of NSCLC and there is an increasing trend towards targeted therapy.

It is common practice to evaluate for mutations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in patients diagnosed with adenocarcinoma of lung origin. In advanced disease, chemotherapy prolongs survival and improves quality of life, and may provide palliation for local symptoms.

Palliative radiotherapy can be used for symptoms such as haemoptysis, focal pain or brain metastasis. The minority of patients with NSCLC (20-30%) are eligible for radical surgery. In England, only 10% of all patients have surgical resection.

Most patients will benefit from palliative care input - this should be introduced formally at an early stage of the pathway.2

Management of SCLC

SCLC is an aggressive malignancy that progresses rapidly. About two-thirds of patients present with extensive disease. Only 5% of patients with SCLC are eligible for resection.

Patients with limited disease, defined as disease involving one hemithorax, are treated with a combination of chemotherapy and radiotherapy because it has been shown that the addition of radiotherapy improves survival.

Extensive stage SCLC is treated with chemotherapy alone. The brain is often the site of initial relapse and prophylactic cranial irradiation has been shown to decrease the incidence of brain metastases and to prolong the patient's survival.

SCLC is a chemosensitive malignancy, with response rates of up to 85 per cent. Unfortunately disease relapse is common.

Managing symptoms

There are a number of options for relieving symptoms secondary to central airway obstruction, including laser, cryotherapy, brachytherapy, tumour debulking and stent placement. In the case of symptomatic brain metastases, palliative radiotherapy can be offered.

Symptomatic malignant pleural effusions (MPE) can be managed effectively by aspiration with or without pleurodesis. Pleurodesis is successful at preventing symptomatic recurrence of MPE in around 70% of cases.

Should there be radiographic evidence of trapped lung after thoracocentesis, an indwelling pleural catheter can be inserted. This is a tunnelled catheter that allows the patient or a family member to intermittently drain the effusion as it reaccumulates in the comfort of their own home.

While these interventions have no impact on survival, specific focal symptoms should be managed aggressively to improve quality of life.

Important Most patients will benefit from palliative care input - this should be introduced formally at an early stage of the pathway.

Section 4: Prognosis

The prognosis for patients with lung cancer is poor, with a 9.5% five-year survival.


Multiple complications can result from lung cancer, including thoracic and extra-thoracic complications.

At diagnosis, 20-30% of patients will present with malignant central airway obstruction, which may result in postobstructive atelectasis and pneumonia. After initial therapy, up to 50% of patients will present again with a local recurrence. In addition, 30% of all lung cancer patients will present with some form of haemorrhage.

Cancer patients are also at risk of pulmonary emboli and this should be considered in patients with increased dyspnoea,chest pain or haemoptysis.

There is also increased incidence of pleural effusions and superior vena caval obstruction. Extrathoracic complications vary depending on the site of metastatic disease, for example, pain from bony metastatic disease, headache and blurred vision from brain metastases.

Paraneoplastic syndromes can result in endocrine disturbances such as hyponatraemia, hypercalcaemia, Cushing's syndrome, neurological signs and symptoms (Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration), or musculoskeletal diseases such as polymyositis and dermatomyositis.


Follow-up arrangements depend on the administered treatment modality and whether it was used with radical or palliative intent.

When curative/radical treatment has been administered, the emphasis of follow-up will be on the detection of recurrent disease. The National Comprehensive Cancer Network guidelines suggest a clinic review and CT thorax every six to 12 months for the first two years, and annually thereafter.

If there has been active treatment with palliative intent, the focus will be on the detection of disease progression and control of symptoms.

If no active treatment has been offered, follow-up will be directed towards symptom control and monitoring.

Specialist input

All patients who are treated for lung cancer should be offered specialist follow-up within six weeks of completing their course of treatment.

All patients should then be offered regular, continuing follow-up. Lung cancer clinical nurse specialists should remain an important component of patient care at all stages of the patient pathway.

 Important! Cancer patients are also at risk of pulmonary emboli and this should be considered in patients with increased dyspnoeachest pain or haemoptysis.

Section 5: Case study

A 76-year-old male, with no significant comorbidity and a PS score of one, was referred under the two-week rule with a three-week history of streaky haemoptysis. The initial chest X-ray suggested right hilar enlargement. After the initial clinical assessment, a CT was arranged.This demonstrated extensive mediastinal and hilar adenopathy with associated supra-clavicular lymphadenopathy and liver metastases.

SCLC with metastases

Urgent fine needle aspiration of the supraclavicular lymph nodes confirmed a diagnosis of extensive stage SCLC with liver metastases. In accordance with NICE guidelines, the patient was seen within one week by an oncologist and commenced on systemic chemotherapy.

The patient completed six courses of platinum-based chemotherapy. He had a good clinical and radiological response, so prophylactic cranial irradiation was administered.

After a three-month period of stability, he presented to his GP with worsening shortness of breath. CT revealed progression within the thorax, with central airway obstruction and a large pleural effusion.

He was reviewed by an oncologist, who felt that the short interval before relapse and a deterioration in PS (now three) contraindicated further chemotherapy. The central airway obstruction was debulked and a stent placed to maintain airway patency. The pleural fluid was aspirated and pleurodesis performed. This resulted in good symptomatic improvement and the patient was discharged. He remained at home with community support and palliative input until his death one month later.

Section 6: Evidence base

Clinical trials

  • Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733-42.
  • Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-57
  • Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. The Lancet 2009; 374: 1432-40
  • Kawaguchi T, Koh Y et al. Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study. J Clin Oncol 2016 Jul 1;34(19):2247-57
  • Senthi S, Lagerwaard FJ et al. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol. 2012 Aug;13(8):802-9


  • Diagnosis and management of lung cancer: ACCP Guidelines (third edition). Chest 2007; 132 (3 suppl).
  • NICE. Lung cancer. The diagnosis and treatment of lung cancer. CG121. London, NICE, April 2011.


  • Mason RJ, Broaddus VC, Murray JF et al. Murray and Nadel's Textbook of Respiratory Medicine (fifth edition). Saunders, 2010.



  1. Peto R, Darby S, Deo H et al. BMJ 2000; 321: 323-329.
  2. Temel JS, Greer JA, Muzikansky A et al. N Engl J Med 2010; 363: 733-742.
  3. Navani N, Nankivell M, Lawrence DR et al. The Lancet 2015; 3(4): 282–289.

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This is an updated version of an article first published in June 2011.

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