9th January 2024

Diagnosis

Lung cancer should be investigated in any individual who has chest X-ray findings suggestive of lung cancer, or anyone who is aged over 40 with unexplained haemoptysis.

A chest X-ray is also required in:

• Patients over the age of 40 who have recurrent chest infections, nail clubbing, supraclavicular lymphadenopathy or persistent cervical lymphadenopathy or thrombocytosis
• Patients with a history of smoking who develop a cough, fatigue, dyspnoea, chest pain, weight loss or loss of appetite

Patients who develop an unprovoked deep vein thrombosis (DVT) should have a thorough history taken, and if suspicious for lung cancer, this should be investigated.

Investigations

Blood tests

Blood tests alone are not diagnostic of lung cancer but are useful in ruling out other conditions.

• FBC, CRP (with differential and platelet count)
• U&Es
• Bone Profile
  • Bone metastasis can result in hypercalcaemia
• LFTs
  • If there is liver metastasis, then LFTs can be deranged. ALP can be elevated in bone metastasis.
• GGT
  • If ALP is elevated but GGT is normal, bone metastasis should be considered.

Imaging

Chest radiographs are the first-line imaging modality and are used to identify any large lesions. A pleural effusion may be present. In addition, it is helpful to have a baseline radiograph with which future scans can be compared.

If the chest X-ray is suspicious of lung cancer, then chest computed tomography (CT) with contrast enhancement is used within 72 hours if arranged by primary care or 24 hours if an inpatient. The CT scan covers the neck, chest, abdomen and pelvis to assess for any possible metastasis.

CT imaging allows staging of the lung cancer, and for this, the TNM staging system is used. This staging is used to determine if there is curative intent, and if so, a PET CT is organised.

CT brain imaging is also used if patients have neurological symptoms or if there is treatment considered with curative intent. If metastases are found, MRI imaging is used.

X-ray imaging of joints/bones can be considered if there is suspicion of bone metastasis.

TNM Staging

The TNM system looks at the tumour size, lymph node involvement and metastasis. The ‘T’ in the system is often followed with a suffix numeral and letter, for example, T1b, T2a. This helps categorise the physical size of the tumour.

Tx- The imaging modality could not assess the primary tumour, or it can’t be seen

T0 – There is no sign of cancer

T1 – Cancer is contained within the lung and is less than 3cm

T2 – Cancer involves the ipsilateral main bronchus or visceral pleura, or there is ipsilateral atelectasis. The lesion is between 3cm and 5cm.

T3 – Cancer involves the chest wall, parietal pleura, phrenic nerve or pericardium. If there is more than one tumour in the same lobe, this is also classed as T3. The lesion is between 5cm and 7cm.

T4 – Cancer involves the mediastinum, diaphragm, heart, great vessels, recurrent laryngeal nerve, carina, trachea, oesophagus, spine, or another tumour is in a different lobe of the ipsilateral lung. The lesion is greater than 7cm.

Nx – Lymph nodes could not be assessed

N0 – Regional lymph nodes not involved

N1 – Ipsilateral peribronchial and/or ipsilateral hilar node involvement

N2 – Ipsilateral mediastinal and/or subcarinal lymph node involvement.

N3 – Contralateral mediastinal/hilar, ipsilateral or contralateral scalene/supraclavicular node involvement

M0 – No distant metastasis

M1 – Distant metastasis present

Tissue Sampling – Bronchoscopy, EBUS, Tracheostomy, Pleural Aspiration

A biopsy of the suspected cancer should be obtained if possible. Depending on the location of the lesion, endobronchial ultrasound (EBUS), CT-guided biopsy or bronchoscopy could be used to obtain the tissue sample.

The tissue is sent for histology and molecular profiling. This allows visualisation of the type of tumour (e.g. SCLC) and facilitates targeted chemotherapy if certain mutations are present.

• For paratracheal or peri-bronchial lung lesions, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used.
• For central lesions, if the patient has known metastasis and thus node sampling isn’t needed, bronchoscopy should be used.
• For peripheral lesions, image-guided biopsy should be used, for example, CT-guided biopsy.
• In patients who have negative EBUS tissue sampling but clinical suspicion of nodal involvement is high, mediastinoscopy can be considered.
• For enlarged or PET-CT positive intrathoracic lymph nodes, EBUS-TBNA or EBUS-fine needle aspiration (EBUS-FNA) should be used.
• In patients who decline invasive testing or those with central masses should have sputum sent off for cytology.
• To make an accurate diagnosis, tissue sampling of the lesion is required, but in patients with advanced disease who are very unwell, the diagnosis is sometimes presumed from imaging alone.

Pulmonary Function Tests / Cardiopulmonary Exercise Testing

All patients who are being considered for treatment with curative intent should have spirometry and TLCO testing. Surgery should be offered to patients if the FEV1 is normal and cardiopulmonary exercise testing shows a VO2 max of 15ml/kg/minute. Patients with FEV1 or TLCO <30% should only be considered for surgery after discussions about the risk of dyspnoea and other complications.

The FEV1 value is important in determining a patient’s suitability for surgery. An FEV1 of < 1.5 is contraindication for a lobectomy, whilst an FEV1 is a contraindication for a pneumonectomy.

References

• Suspected cancer: recognition and referral – NICE guideline [NG12] https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer#lung-and-pleural-cancers (accessed October 2022)
• UpToDate [Internet]. Uptodate.com. 2022 [cited 10 October 2022]. Available from:  https://www.uptodate.com/contents/overview-of-the-initial-evaluation-diagnosis-and-staging-of-patients-with-suspected-lung-cancer
• Lababede O, Meziane MA. The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and Diagrams. The Oncologist. 2018 Apr 12;23(7):844–8.