Lung cancer

The management guidelines summary for small-cell lung cancers (SCLCs) and non-small-cell lung cancers (NSCLCs) in this article are taken from the guidelines published by the National Institute for Health and Care Excellence (NICE).¹ Local agreed guidelines should be followed where applicable.

See also the separate Malignant Mesothelioma article - a tumour of mesothelial cells which usually occurs in the pleura but may also occur elsewhere - eg, the peritoneum.

What is lung cancer?²

Approximately 95% of all primary lung tumours are bronchial carcinomas. Metastases in the lung are common and typical sites for the primary tumour include the kidney, prostate, breast, bone, gastrointestinal tract, cervix and ovary. Metastases usually develop in the parenchyma and are relatively asymptomatic even when metastases are extensive. Carcinoma of the stomach, pancreas and breast may involve mediastinal glands and spread along the lung lymphatics (lymphangitis carcinomatosa), causing progressive and severe breathlessness.

Primary bronchial cancers are classified as follows:

SCLCs

These account for about 15-20% of cases:

• Also called oat-cell carcinoma, arising from Kulchitsky cells, which are part of the amine precursor uptake and decarboxylation (APUD) endocrine system. APUD cells manufacture polypeptides and amines which act as hormones or neurotransmitters.

• Rapidly growing and highly malignant, they spread early and are almost always inoperable at presentation.

• They respond to chemotherapy but the prognosis is poor.

NSCLCs

These account for 80-85% of cases. The NSCLCs are often grouped together when treatment is being considered. NSCLCs include:

• Squamous:
  

  • Develop in the flat cells that cover the surface of the airways. Tend to grow near the centre of the lung.

  • Most present as obstructive lesions of the bronchus, leading to infection.

  • Local spread is common but widespread metastases occur relatively late.

• Adenocarcinoma:
  

  • The most common type, and starts in the mucus gland cells in the lining of the airways.

  • It is the most common bronchial carcinoma associated with asbestos and is more common in non-smokers, compared with other cell types.

  • Invasion of the pleura and the mediastinal lymph nodes is common.

  • It often metastasises to the brain and bones.

• Large-cell:
  

  • Are less differentiated forms of squamous cell and adenocarcinomas.

  • Large-cell carcinomas metastasise early.

• Carcinoid tumours (7% of NSCLCs).

• Bronchoalveolar cell tumours (4% of NSCLCs):
  

  • Occurs either as a peripheral solitary nodule or as diffuse nodular lesions.

How common is lung cancer? (Epidemiology)²

• Lung cancer is the third most common cancer in the UK, accounting for 13% of all new cancer cases (2016-2018).

• Incidence rates for lung cancer in the UK are highest in people aged 85 to 89 (2016-2018). Each year more than 4 in 10 (44%) of all new lung cancer cases in the UK are diagnosed in people aged 75 and over (2016-2018).

• Since the early 1990s, lung cancer incidence rates have decreased by around a tenth (9%) in the UK. Rates in females have increased by around a third (32%), and rates in males have decreased by around a third (34%) (2016-2018).

• Incidence rates for lung cancer are projected to fall by 7% in the UK between 2014 and 2035, to 88 cases per 100,000 people by 2035.

• The most common specific location for lung cancers in the UK is the upper lobe of the bronchus or lung (2016-2018).

• Lung cancer incidence rates in England in females are 174% higher in the most deprived quintile compared with the least, and in males are 168% higher in the most deprived quintile compared with the least (2013-2017).

• Incidence rates for lung cancer are lower in the Asian and Black ethnic groups, and in people of mixed or multiple ethnicity, compared with the White ethnic group, in England (2013-2017).

Risk factors

• A person’s risk of developing cancer depends on many factors, including age, genetics and exposure to risk factors (including some potentially avoidable lifestyle factors).

• 1 in 13 UK males and 1 in 15 UK females will be diagnosed with lung cancer in their lifetime.

• 79% of lung cancer cases in the UK are preventable.

• 72% of lung cancer cases in the UK are caused by smoking.

• 5% of lung cancer cases in the UK are caused by ionising radiation.

• 13% of lung cancer cases in the UK are caused by workplace exposures.

• 8% of lung cancer cases in the UK are caused by air pollution.

Lung cancer symptoms (presentation)¹

• Initial symptoms and signs include:
  

  • Cough.

  • Dyspnoea.

  • Weight loss.

  • Chest pain.

  • Haemoptysis.

  • Bone pain.

  • Finger clubbing.

  • Fever.

  • Weakness.

  • Superior vena cava obstruction.

  • Dysphagia.

  • Headache.

  • Nausea and vomiting.

  • Hoarseness (recurrent laryngeal nerve involvement).

  • Wheezing and stridor.

• Other presentations include recurrent or slowly resolving pneumonia, anorexia, hypertrophic pulmonary osteoarthropathy and supraclavicular or axillary lymphadenopathy.

• Chest signs: sometimes no signs; otherwise, consolidation, collapse, pleural effusion.

• Metastatic disease: bone tenderness, hepatomegaly, confusion, fits, focal neurological deficit, cerebellar syndrome, proximal myopathy, peripheral neuropathy.

Differential diagnosis

Other causes of a 'coin lesion' (solitary, round, circumscribed shadow in the lung field on CXR):

• Secondary malignancy.

• Arteriovenous malformation.

• Pulmonary hamartoma:
  

  • Rare, benign tumour.

  • CT scan shows lobulated mass with flecks of calcification.

  • Often excised to exclude malignancy.

• Bronchial adenoma:
  

  • Rare, slow-growing tumour.

  • 90% are carcinoid tumours; 10% are cylindromas.

  • Treatment is surgery.

• Abscesses.

• Granuloma - eg, tuberculosis.

• Encysted effusion (fluid, blood, pus).

• Cyst.

• Foreign body.

• Skin tumour (eg, seborrhoeic wart).

Referral³

Refer people, using a suspected cancer pathway referral (for an appointment within two weeks) for lung cancer, if they:

• Have chest X-ray findings that suggest lung cancer; or

• Are aged 40 and over with unexplained haemoptysis.

Offer an urgent chest X-ray (to be done within two weeks) to assess for lung cancer in people aged 40 and over if they have two or more of the following unexplained symptoms, or if they have ever smoked and have one or more of the following unexplained symptoms:

• Cough.

• Fatigue.

• Shortness of breath.

• Chest pain.

• Weight loss.

• Appetite loss.

Consider an urgent chest X-ray (to be done within two weeks) to assess for lung cancer in people aged 40 and over with any of the following:

• Persistent or recurrent chest infection.

• Finger clubbing.

• Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy.

• Chest signs consistent with lung cancer.

• Thrombocytosis.

Investigations¹

• CXR: this may show a peripheral circular opacity, hilar enlargement, consolidation, pleural effusion or bony secondaries.

• Sputum cytology only if there are centrally placed nodules or masses and the person declines or cannot tolerate bronchoscopy or other invasive tests.

• Contrast-enhanced chest CT scan (including liver, adrenals and lower neck) to further the diagnosis and stage the disease.

• When assessing mediastinal and chest wall invasion, CT alone may not be reliable and other techniques such as ultrasound should be considered if there is doubt.

• Surgical assessment may be necessary if there are no contra-indications to resection.

• All who could potentially have treatment with curative intent should be offered positron-emission tomography CT (PET-CT) before treatment.

• MRI should not be used routinely to assess the stage of the primary tumour (T-stage) in non-small-cell lung cancer (NSCLC), but should be used when necessary to assess the extent of disease, for people with superior sulcus tumours.

• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) should be used for biopsy of paratracheal and peri-bronchial intra-parenchymal lung lesions.

• Contrast-enhanced CT of the chest, liver, adrenals and lower neck should be performed before any biopsy procedure.

• Peripheral primary tumour:

  • Image-guided biopsy when treatment can be planned on the basis of this test.

  • Biopsy any enlarged intrathoracic nodes (10 mm or larger maximum short axis on CT) or other lesions in preference to the primary lesion if determination of nodal stage affects treatment.

• Central primary tumour:

  • Flexible bronchoscopy should be offered to people with central lesions on CT if nodal staging does not influence treatment.

• Intrathoracic lymph node assessment

  • PET-CT is the preferred first test after CT with a low probability of nodal malignancy (lymph nodes below 10 mm maximum short axis on CT), for people who could potentially have treatment with curative intent.

  • PET-CT (if not already done), followed by EBUS-TBNA and/or EUS-FNA, should be offered to people who have enlarged intrathoracic lymph nodes (lymph nodes greater than or equal to 10 mm short axis on CT) and who could potentially have treatment with curative intent.

  • PET-CT-positive or enlarged intrathoracic nodes should be evaluated by sampling any suspicious node on CT, PET or USS with EBUS-TBNA and/or EUS-FNA if nodal status would affect the treatment plan.

  • Surgical mediastinal staging should be considered for people with a negative EBUS-TBNA or EUS-FNA if clinical suspicion of nodal malignancy is high and nodal status would affect their treatment plan.

• Further staging:

  • Confirm isolated distant metastases/synchronous tumours by biopsy or further imaging (for example, MRI or PET-CT) in people considered for treatment with curative intent.

  • Dedicated brain imaging should not be offered to people with clinical stage I NSCLC who have no neurological symptoms and are having treatment with curative intent.
    Contrast-enhanced brain CT should be offered to people with clinical stage II NSCLC who are having treatment with curative intent. If CT shows suspected brain metastases, contrast-enhanced brain MRI should be offered.

  • Contrast-enhanced brain MRI for people with stage III NSCLC who are having treatment with curative intent.

  • If clinical features suggestive of intracranial pathology: CT of the head followed by MRI if normal, or MRI as an initial test.

  • X-ray as the first test for people with localised signs or symptoms of bone metastasis. If results are negative or inconclusive, bone scintigraphy or an MRI scan. Avoid bone scintigraphy if PET-CT has not shown bone metastases.

EarlyCDT-Lung for assessing risk of lung cancer in solid lung nodules - not recommended by NICE⁴
Early cancer detection lung testing (EarlyCDT-Lung) is used to assess the risk of lung cancer in solid lung nodules. Accurate risk assessment can prevent delayed treatment of malignant nodules or unnecessary biopsies of benign nodules. However, the manufacturer of the technology intends for EarlyCDT-Lung results to be used to update a person's existing lung cancer risk assessment.

Most of the existing data do not represent the intended use of the test in updating estimates of lung cancer risk. It is also unclear how EarlyCDT-Lung will affect lung nodule management in the NHS, or its impact on long-term patient outcomes.

As such, NICE has determined that there is not enough evidence to recommend routine use of EarlyCDT-Lung for assessing the risk of lung cancer in solid lung nodules.

Staging and management of non-small-cell lung cancer¹

Thoracic surgery is considered the standard of care for people with early-stage lung cancer who are deemed fit enough. Modern surgical techniques have been developed, including less invasive video-assisted thoracoscopic surgery, for lung resections, that are changing the boundaries of surgical fitness.⁵

NICE has produced a number of technology appraisals regarding recommended treatments for lung cancer. Some of these appraisals are mentioned in the following section. For more information on these and other technology appraisals, see the link to the NICE list of lung cancer technology appraisals in the link provided in the Further Reading section below.

Staging

• Follows the 'tumour, node, metastasis' (TNM7) classification:⁵
  

  • Tumour (T):
    

    • TX - positive malignant cytology results, no lesion seen.

    • T0 - no evidence of primary tumour.

    • Tis - adenocarcinoma in situ.

    • T1 - diameter smaller than, or equal to, 3 cm.

      • T1a - tumour ≤1 cm.

      • T1b - tumour >1 cm and ≤2 cm.

      • T1c - tumour >2 cm and ≤3 cm.

    • T2:
      

      • Associated with lung atelectasis or pneumonitis.

      • Tumour with any of the following features of size or extent:
        

        • Over 3 cm but less than 5 cm in greatest dimension.

        • Involves the main bronchus.

        • Invades the visceral pleura.

      • T2a - tumour >3 cm and ≤4 cm.

      • T2b - tumour >4 cm and ≤5 cm.

    • T3:
      

      • Tumour >5 and ≤7 cm.

    • T4:

      • Tumour >7 cm.

      • Diaphragmatic invasion. Invasion of mediastinal organs (eg, the oesophagus, trachea, great vessels, heart), malignant pleural effusion, recurrent laryngeal nerve, or satellite nodule(s) within the primary lobe or separate tumour nodule(s) in different ipsilateral lobe.

  • Regional lymph node involvement (N):
    

    • N0 - no lymph nodes involved.

    • N1 - ipsilateral bronchopulmonary or hilar nodes involved.

    • N2 - ipsilateral mediastinal or subcarinal nodes.

    • N3 - contralateral mediastinal, hilar, any supraclavicular nodes involved.

  • Metastatic involvement (M):
    

    • M0 - no metastases.

    • M1 - metastases present.

    • M1a - separate tumour nodule(s) in contralateral lobe or tumour with malignant pleural (or pericardial) effusion.

    • M1b - distant metastasis.

• Stage groupings:
  

  • IA - T1 N0 M0.

  • IB - T2 N0 M0.

  • IIA - T1 N1 M0.

  • IIB - T2 N1 M0 or T3 N0 M0.

  • IIIA - T1-3 N2 M0 or T3 N1 M0.

  • IIIB - any T4 or any N3 M0.

  • IV - any M1.

Management

• Patients with lung cancer who smoke, in particular those with a better prognosis, should be encouraged to stop smoking. They should be advised that smoking cessation reduces post-surgery lung complications. Surgery should not, however, be postponed until the patient has stopped smoking.

• For patients with NSCLC being considered for curative surgery, a global risk assessment tool (eg, Thoracoscore) should be used to calculate the risk of death. The patient should be advised of this score before being asked to sign the consent form.⁶

• Lung function tests should be performed on all patients pre-surgery.

• Cardiovascular risk should be assessed, especially in patients with a history of cardiovascular comorbidities.

Surgery

• If well enough and if treatment with curative intent is suitable, lobectomy (either open or thoracoscopic).

• More extensive surgery (broncho-angioplastic surgery, bilobectomy, pneumonectomy) only when needed to obtain clear margins.

• Hilar and mediastinal lymph node sampling or en bloc resection for all people having surgery with curative intent.

• For people with T3 NSCLC with chest wall involvement who are having surgery, aim for complete resection of the tumour using either extrapleural or en bloc chest wall resection.

Surgery or radiotherapy for people not having lobectomy

• For people with stage I-IIA (T1a-T2b, N0, M0) NSCLC who decline lobectomy or it is contra-indicated, radical radiotherapy with stereotactic ablative radiotherapy (SABR) or sublobar resection.

Radical radiotherapy for people not having surgery

• All people should have pulmonary function tests (including lung volumes and transfer factor) before radical radiotherapy for NSCLC.

• For people with stage I-IIA (T1a-T2b, N0, M0) NSCLC who decline surgery or surgery is contra-indicated, offer SABR. If SABR is contra-indicated, offer either conventional or hyperfractionated radiotherapy.

• Stage IIIA NSCLC who cannot tolerate or decline chemoradiotherapy (with or without surgery): consider radical radiotherapy (either conventional or hyperfractionated).

• Stage IIIB NSCLC who cannot tolerate or decline chemoradiotherapy: consider radical radiotherapy (conventional or hyperfractionated).

Combination treatment for non-small-cell lung cancer

• Consider chemoradiotherapy for stage II or III NSCLC that are not suitable or decline surgery.

• Postoperative chemotherapy if good performance status (WHO 0 or 1) and T1a-4, N1-2, M0 NSCLC.

• Postoperative chemotherapy if good performance status (WHO 0 or 1) and T2b-4, N0, M0 NSCLC with tumours greater than 4 cm in diameter.

• Cisplatin-based combination chemotherapy regimen for adjuvant chemotherapy.

• Stage I-II NSCLC suitable for surgery, do not offer neo-adjuvant treatment outside a clinical trial.

• Treat Pancoast tumours in the same way as other types of NSCLC. Multimodality therapy according to resectability, stage of the tumour and performance status of the person.

• For operable stage IIIA-N2 NSCLC patients who can have surgery and are well enough for multimodality therapy, consider chemoradiotherapy with surgery.

• Chemoradiotherapy with surgery improves progression-free survival, and chemoradiotherapy with surgery may improve overall survival.

• Stage IIIA-N2 NSCLC having chemoradiotherapy and surgery, ensure surgery is scheduled for 3 to 5 weeks after the chemoradiotherapy.

Systemic anti-cancer therapy (SACT) for advanced non-small-cell lung cancer
NICE has produced summaries of the treatment pathways bringing together NICE-recommended treatment options from the clinical guideline and relevant technology appraisal guidance.

Surgical resection

• The treatment of choice for patients with stage I or stage II disease. Lobar resection is the procedure of choice. Patients with stage I or stage II disease who would not tolerate lobectomy because of comorbid disease or pulmonary compromise, should be considered for limited resection or radical radiotherapy.

• More extensive surgery (eg, broncho-angioplastic surgery, bilobectomy, pneumonectomy) should only be undertaken if such procedures are necessary to obtain tumour-free margins.

• All patients undergoing surgical resection should have hilar and mediastinal lymph node sampling to provide accurate pathological staging.

• In patients with stage IIIA NSCLC, surgery alone is associated with a relatively poor prognosis.

Radiotherapy

• This should be offered to all patients with stage I-III NSCLC who are not suitable for surgery.

• Radical radiotherapy is indicated for patients with stage I, II or III NSCLC who have good performance status and whose disease can be encompassed in a radiotherapy treatment volume without undue risk of normal tissue damage.

• All patients should undergo pulmonary function tests (including lung volumes and transfer factor) before having radical radiotherapy.

• Patients who have poor lung function but are otherwise suitable for radical radiotherapy should still be offered radiotherapy, provided the volume of irradiated lung is small.

Chemotherapy⁷

• Chemotherapy should be offered to patients with stage III or IV NSCLC and good performance status, to improve survival, disease control and quality of life.

• Second-generation chemotherapeutic agents include ifosfamide, vinblastine, vindesine, mitomycin C and platinums (carboplatin and cisplatin). More recently, the third-generation drugs (gemcitabine, paclitaxel, vinorelbine and docetaxel) have been shown to have significant activity against NSCLC, alone or in combination.

• Chemotherapy for advanced NSCLC should be a combination of a single third-generation drug (docetaxel, gemcitabine, paclitaxel or vinorelbine) plus a platinum drug. Either carboplatin or cisplatin may be administered. Patients who are unable to tolerate a platinum combination may be offered single-agent chemotherapy with a third-generation drug. Docetaxel, gefitinib and erlotinib improve overall survival in patients with NSCLC.⁸

• Docetaxel monotherapy should be considered if second-line treatment is appropriate for patients with locally advanced or metastatic NSCLC in whom relapse has occurred after previous chemotherapy.

• Pemetrexed:⁹

  • Pemetrexed in combination with cisplatin is recommended as an option for the first-line treatment of patients with locally advanced or metastatic NSCLC only if the histology of the tumour has been confirmed as adenocarcinoma or large-cell carcinoma.¹⁰

  • NICE recommends pemetrexed as an option for the maintenance treatment of people with locally advanced or metastatic NSCLC other than predominantly squamous cell histology if disease has not progressed immediately following platinum-based chemotherapy in combination with gemcitabine, paclitaxel or docetaxel.¹¹

• Erlotinib:¹² :

  • Erlotinib is recommended as as a possible treatment for people with locally advanced or metastatic NSCLC that has already been treated with non-targeted chemotherapy because of delayed confirmation of EGFR‑TK mutation status, if:

    • Their cancer tests positive for the EGFR‑TK mutation; or

    • it is not known if the cancer is EGFR‑TK mutation‑positive because of problems with the test; and:

      • The cancer is very likely to be EGFR‑TK mutation‑positive.

      • It responds to the first two cycles of treatment with erlotinib.

• Afatinib:¹³

  • Afatinib is recommended by NICE for the treatment of locally advanced or metastatic NSCLC with activating EGFR mutations, in patients who have not previously been treated with EGFR-TK inhibitor.

• Crizotinib:^{7 14}

  • This is recommended by NICE for the treatment of previously treated anaplastic lymphoma kinase (ALK)-positive advanced NSCLC.

• Gefitinib:

  • Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic NSCLC if they test positive for the EGFR-TK mutation.¹⁵

  • However, NICE does not recommend the NHS use of gefitinib for the second-line treatment of locally advanced or metastatic NSCLC.

• Bevacizumab:

  • Bevacizumab, in combination with platinum-based chemotherapy, is licensed for first-line treatment of unresectable advanced, metastatic or recurrent NSCLC other than predominantly squamous cell histology.

  • However, bevacizumab is currently not recommended by NICE for the treatment of lung cancer.

• Nintedanib:

  • Nintedanib is licensed for the treatment of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma histology after first-line chemotherapy (in combination with docetaxel) initiated under specialist supervision).It is recommended by NICE.¹⁶

• Nivolumab:¹⁷

  • Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response (including the anti-tumour immune response) resulting in decreased tumor growth.

  • NICE recommends that nivolumab should be an option for treating locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) in adults after chemotherapy, only if their tumours are PD-L1 positive, it is stopped at two years of uninterrupted treatment, or earlier if their disease progresses, and the patient has not had a PD-1 or PD-L1 inhibitor before.

• Osimertinib:²⁰

  • NICE has stated that osimertinib is only recommended for use in adults with stage 1b-3a NSCLC as adjuvant treatment following complete tumour resection:

    • If they have (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

    • If the drug is stopped after three years (or earlier if toxicity is unacceptable or if disease recurs).
      

• Tepotinib:

  • Tepotinib is a kinase inhibitor which targets mesenchymal-epithelial transition (MET) factor gene including variants with exon 14 skipping alterations. This inhibits tumour cell proliferation.

  • Tepotinib is recommended as an option for treating advanced non-small-cell lung cancer (NSCLC) with METex14 skipping alterations in adults.²¹
    

• Durvalumab:

  • Durvalumab is a selective human monoclonal antibody that potentiates an immune response to tumour cells. It selectively binds to programmed cell death ligand (PD-L1).

  • It is now considered an option for treating locally advanced unresectable NSCLC in adults whose tumours express programmed cell death ligand 1 (PD‑L1) on 1% or more of cells and whose disease has not progressed after platinum-based chemoradiation.

  • Durvalumab is recommended as an option for treating locally advanced unresectable non-small-cell lung cancer (NSCLC) in adults whose tumours express programmed cell death ligand 1 (PD-L1) on 1% or more of cells and whose disease has not progressed after platinum-based chemoradiation, only if they have had concurrent platinum-based chemoradiation.²²

• Targeted therapy - this relies on the use of biomarkers to identify specific mutations. Personalised treatments aimed at these mutations can then be developed.²⁵

• Combination therapy:
  

  • Postoperative radiotherapy should be considered after incomplete resection of the primary tumour for patients with NSCLC, with the aim of improving local control.

  • Adjuvant chemotherapy should be offered to NSCLC patients who have had a complete resection.

  • Patients with stage III NSCLC, who are not suitable for surgery but are eligible for radical radiotherapy, should be offered sequential chemotherapy and radical radiotherapy.

• Percutaneous radiofrequency ablation:
  

  • Percutaneous radiofrequency ablation may be used in patients with primary or secondary lung cancers. There is a small incidence of pneumothorax, which may have serious implications for patients with already compromised respiratory reserve.²⁶

Microwave ablation for primary or metastatic cancer in the lung²⁷
NICE has issued guidance on this procedure, which is usually carried out under general anaesthetic. They note that while evidence for the safety of this procedure to treat primary lung cancer and metastases in the lung is adequate, microwave ablation can cause infrequent serious complications. In addition, while evidence on efficacy shows it reduces tumour size, there is limited evidence on improvement in survival, long-term outcomes and quality of life. Therefore, NICE recommends the procedure only if there are special arrangements for clinical governance, consent, and audit or research.

Staging and management of small-cell lung cancer¹

Staging

• Staging investigations include serum lactate dehydrogenase, LFTs and serum sodium.

• Should be staged by a contrast-enhanced CT scan of the patient's chest, liver and adrenal glands and by selected imaging of any symptomatic area. A two-stage system of staging is used:
  

  • Limited-stage disease - this includes patients with disease that:
    

    • Is confined to one hemithorax.

    • Involves ipsilateral hilar lymph nodes.

    • Involves ipsilateral and contralateral supraclavicular lymph nodes.

    • Involves ipsilateral and contralateral mediastinal lymph nodes.

    • Can be with or without ipsilateral pleural effusions, independent of cytology.

  • Extensive-stage disease - disease at sites beyond the definition of limited disease. This includes patients with:
    

    • Metastatic lesions in the contralateral lung.

    • Distant metastatic involvement (eg, brain, bone, liver or adrenal glands).

Management

First-line treatment for limited-stage disease small-cell lung cancer

• Limited-stage disease SCLC (T1-4, N0-3, M0) 4 to 6 cycles of cisplatin-based combination chemotherapy. Substitute carboplatin if there is impaired renal function, poor performance status (WHO 2 or more) or significant comorbidity.

• Radiotherapy with concurrent chemotherapy if there is limited-stage disease SCLC (T1-4, N0-3, M0) and a WHO performance status of 0 or 1, if present with disease that can be encompassed in a radical thoracic radiotherapy volume.

• Sequential radical thoracic radiotherapy if there is limited-stage disease SCLC (T1-4, N0-3, M0) in patients who are not well enough for concurrent chemoradiotherapy but who respond to chemotherapy.

• Prophylactic cranial irradiation if there is limited-stage disease SCLC and WHO performance status 0 to 2, if disease has not progressed on first-line treatment.

• Surgery for small-cell lung cancer: consider surgery in people with early-stage SCLC (T1-2a, N0, M0).

First-line treatment for extensive-stage disease small-cell lung cancer

• Platinum-based combination chemotherapy if there is extensive-stage disease SCLC (T1-4, N0-3, M1a/b -including cerebral metastases) if fit enough. Assess the person's condition before each cycle of chemotherapy and offer up to a maximum of six cycles, depending on response and toxicity.

• Consider thoracic radiotherapy with prophylactic cranial irradiation if there is extensive-stage disease SCLC and partial or complete response to chemotherapy within the thorax and at distant sites.

• Consider prophylactic cranial irradiation for extensive-stage disease SCLC and WHO performance status 0 to 2, if disease has responded to first-line treatment.

• Maintenance treatment for small-cell lung cancer: only offer maintenance treatment to people with SCLC in the context of a clinical trial.

Second-line treatment for small-cell lung cancer that has relapsed after first-line treatment

• There is very limited evidence that second-line chemotherapy will be of benefit.

• Offer an anthracycline-containing regimen or further treatment with a platinum-based regimen to a maximum of six cycles.

Radiotherapy for palliation of local symptoms
Topotecan²⁸
Oral topotecan is recommended as an option only for people with relapsed small-cell lung cancer for whom re-treatment with the first-line regimen is not considered appropriate, and the combination of cyclophosphamide, doxorubicin and vincristine is contra-indicated.

Supportive and palliative care for lung cancer¹

The following list is a brief outline of certain aspects of palliative care for patients with lung cancer. Guidance is also provided in the British National Formulary.⁷ See also the separate article on Palliative Care.

• Breathlessness:
  

  • Strong opiate - eg, morphine or diamorphine.

  • Non-drug interventions based on psychosocial support, breathing control and coping strategies.

• Bronchial obstruction:
  

  • If there is large airway involvement, monitor (clinically and radiologically) for endobronchial obstruction to ensure treatment is offered early.

  • External beam radiotherapy and/or endobronchial debulking or stenting to people with impending endobronchial obstruction.

• Pleural effusion:
  

  • Pleural aspiration or drainage if there are symptoms of a pleural effusion.

  • If there is benefit symptomatically from aspiration or drainage of fluid, talc pleurodesis for longer-term benefit should be offered.

• Haemoptysis if distressing:
  

  • Radiotherapy.

  • Debulking bronchoscopic procedures should be considered for the relief of bleeding due to an endobronchial tumour within a large airway.

• Cough:
  

  • Opioids (eg, codeine, morphine).

  • Radiotherapy.

• Chest pain:
  

  • Radiotherapy.

• Troublesome hoarseness due to recurrent laryngeal nerve palsy:
  

  • Refer to an ear, nose and throat specialist for advice.

• Superior vena cava obstruction:
  

  • Chemotherapy and radiotherapy according to the stage of disease and performance status.

  • Stent insertion should be considered for the immediate relief of severe symptoms of superior vena cava obstruction or following failure of earlier treatments.²⁹

• Bone pain:
  

  • Single-fraction radiotherapy if bone metastasis needs palliation and standard analgesic treatments are inadequate.

• Cerebral metastases:
  

  • Dexamethasone and radiotherapy should be considered.

• Spinal cord compression:
  

  • This is a medical emergency and immediate treatment (within 24 hours), with corticosteroids, radiotherapy and surgery where appropriate, is recommended.

  • Patients with spinal cord compression should have an early referral to an oncology physiotherapist and an occupational therapist for assessment, treatment and rehabilitation.

Other symptoms, including weight loss, loss of appetite, fatigue, depression and difficulty swallowing, should be managed by multidisciplinary groups that include supportive and palliative care professionals.

Complications¹

Local

• Recurrent laryngeal palsy, phrenic nerve palsy, Horner's syndrome, Pancoast's syndrome.

• Cardiovascular: superior vena cava obstruction, pericarditis, atrial fibrillation.

• Rib erosion.

Metastatic

• Brain: confusion, fits, focal neurological deficit, cerebellar syndrome.

• Bone: bone pain, hypercalcaemia.

• Liver: hepatomegaly.

• Adrenal: Addison's disease.

Non-metastatic³⁰

• Endocrine: inappropriate antidiuretic hormone (ADH) secretion, non-metastatic hypercalcaemia, Cushing's syndrome, gynaecomastia, hypoglycaemia, hyperthyroidism.

• Neuromuscular: subacute sensory neuropathy, mononeuritis multiplex, myasthenic syndrome (Lambert-Eaton syndrome), encephalomyelitis, necrotising myelopathy, polymyopathy, motor neurone disease.

• Skeletal: hypertrophic pulmonary osteoarthropathy (joint stiffness and severe pain in the wrists and ankles, sometimes with gynaecomastia. This is usually associated with clubbing of the fingers. It may regress after resection of the lung tumour).

• Renal: glomerulonephritis, nephrotic syndrome.

• Collagen/vascular: myositis, vasculitis, systemic lupus erythematosus, endocarditis.

• Cutaneous: acquired hypertrichosis lanuginosa, erythema gyratum repens, erythema multiforme, tylosis, erythroderma, exfoliative dermatitis, acanthosis nigricans, thrombophlebitis migrans, pruritus, urticaria, dermatomyositis.

• Haematological: anaemia, thrombocytosis, thrombocytopenic purpura, disseminated intravascular coagulation.

Prognosis²

• 40.6% of people diagnosed with lung cancer in England survive their disease for one year or more (2013-2017).

• 16.2% of people diagnosed with lung cancer in England survive their disease for five years or more (2013-2017).

• It is predicted that 9.5% of people diagnosed with lung cancer in England survive their disease for ten years or more (2013-2017).

• Lung cancer survival for females is higher than for males at 1, 5 and 10 years.

• Lung cancer survival in England is higher for people diagnosed at under 40 years of age (2009-2013).

• Almost half of people in England diagnosed with lung cancer aged 15-39 survive their disease for five years or more, compared with more than 5 in 100 people diagnosed aged 80 and over (2009-2013).

• Lung cancer survival has not shown much improvement in the last 40 years in the UK. In the 1970s, fewer than 5 in 100 people diagnosed with lung cancer survived their disease beyond ten years, now it is 5 in 100.

• When diagnosed at its earliest stage, 88% people with lung cancer will survive their disease for one year or more, compared with 19% people when the disease is diagnosed at the latest stage.

• When diagnosed at its earliest stage, 57% of people with lung cancer will survive their disease for five years or more, compared with 3% of people when the disease is diagnosed at the latest stage.

Lung cancer prevention³¹

• More than 80% of lung cancer deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden.

• Also relevant is the reduction of other risk factors, including ionising radiation, workplace exposures and air pollution.

• There is no screening programme in the UK. However, in the USA, the National Lung Screening Trial showed that low-dose computerised tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography.

• The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years.