This is the second most common cancer affecting men (after prostate) and in women is second only to breast cancer. In 2011 there were 44 000 new cases, with 35 000 deaths; the long-term (5-year) survival rate is just 9%.
The incidence of lung cancer in men has been falling since the late 1970s, reflecting a reduction
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in smoking. This fall is yet to be seen in women, al- though the rate of increase is falling. Nine out of 10 cases occur in people 60 years and older.
Aetiology
In the UK, the main aetiological factor is the smok- ing of cigarettes. Passive smoking, air pollution with diesel, petrol and other volatile hydrocarbon fumes, asbestos exposure and exposure to radioactive gases such as radon in uranium mines are also predispos- ing factors. The incidence is higher in urban than in rural populations. There is also a familial element to lung cancer, with a 50% increase in risk if a first- degree relative has it.
Carcinoma of the lung has an extremely poor prog- nosis, and the gravity of this condition should be impressed on all patients who are inveterate smok- ers. The decision whether or not to continue smok- ing depends on the patient, but there is no doubt that the doctor’s advice should be against it. There is an increased incidence of carcinoma of the lung even in patients who smoke only a few cigarettes a day, and this danger is greatly increased in patients smoking more than 20 cigarettes a day for a number of years.
Pathology
Macroscopic appearance
About half the tumours arise in the main bronchi (particularly squamous carcinoma), and 75% are vis- ible at bronchoscopy. The growth may arise peripher- ally (particularly adenocarcinoma) and some appear to be multifocal.
The bronchial wall is narrowed and ulcerated. Sur- rounding lung tissue is invaded by a pale mass of tu- mour, which may undergo necrosis, haemorrhage or abscess formation. The lung segments distal to the occlusion may show collapse, bronchiectasis or ab- scess formation.
Microscopic appearance
1 Small cell carcinoma (12%) (also known as oat cell carcinoma). This has neuroendocrine properties and produces peptides giving rise to paraneo- plastic syndromes (see Chapter 6). The tumour comprises small cells with little cytoplasm. It has a poor prognosis, has generally spread by the time of diagnosis and is best treated by chemotherapy.
2 Non-small cell cancer (NSCLC) (87%).
a Squamous cell carcinoma (40%). Usually oc- curring in the main bronchi, it is mostly poorly
differentiated and arises in an area of squa- mous metaplasia of bronchial epithelium. Fol- lowing successful resection, new primaries are common (10%), reflecting the ‘field change’.
b Adenocarcinoma (37%). A very rapidly grow- ing tumour often found in the periphery of the lung (compare squamous which is central), as- sociated with a large fibrotic (desmoplastic) re- action. This type of lung primary often occurs in non-smokers and is becoming as common as squamous carcinoma.
c Large cell carcinoma (10%). Large cells con- taining abundant cytoplasm and without evi- dence of squamous or glandular differentia- tion; this is also a rapidly growing cancer.
Spread
• Local: to pleura, left recurrent laryngeal nerve, phrenic nerve, pericardium, oesophagus (broncho- oesophageal fistula), sympathetic chain (Horner’s syndrome1) and brachial plexus (Pancoast’s tu- mour2 at lung apex).
• Lymphatic: to mediastinal and cervical nodes.
Compression of the superior vena cava by massive mediastinal node involvement produces gross oedema and cyanosis of the face and upper limbs (superior vena cava syndrome).
• Blood: to bone, brain, liver and adrenals.
• Transcoelomic: pleural seedlings and effusion.
Clinical features
Carcinoma of the lung may present with the following features.
• Local features, namely cough, dyspnoea, haemop- tysis or lung infection. Chest pain suggests spread to pleural surface.
• Secondaries, which are especially likely to occur in the brain, adrenal, liver and bones; thus, the patient may present with evidence of a space- occupying lesion within the skull, pathological fracture, jaundice and hepatomegaly, or adreno- cortical failure.
• Paraneoplastic syndromes due to the remote ef- fects of a hormone or cell product produced by the tumour. Small cell carcinomas often produce adrenocorticotrophic hormone (ACTH), while
1Johann Horner (1831–1886), Professor of Ophthalmology, Zurich, Switzerland.
2Henry Pancoast (1875–1939), Professor of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
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The chest and lungssquamous carcinomas may produce parathor- mone (PTH) and present with hypercalcaemia.
• General effects of neoplasm: loss of weight, anae- mia, cachexia and endocrine disturbances. Pa- tients may also present with bizarre neuropathies and myopathies.
Unfortunately, by the time carcinoma of the lung is diagnosed, most cases are incurable. About half the patients will be found to have inoperable growths when they have had no symptoms at all, with a lesion discovered on routine chest X-ray. Certainly, any middle-aged or elderly person presenting with a res- piratory infection that has continued for more than 2 weeks should have a chest X-ray, and if the symp- toms persist and nothing shows on the chest X-ray, he or she should undergo bronchoscopy.
Cancer of the lung is likely to lead to pulmonary infection and patients often develop clubbing of the fingers, which are usually nicotine stained.
On examination, special attention should be paid to evidence of stridor or hoarseness of the voice due to recurrent laryngeal nerve involvement by the cancer. The heart may be invaded, resulting in atrial fibrillation or cardiac failure. There may be enlarged lymph nodes, especially at the root of the neck, and signs in the chest of consolidation, fluid or collapse.
Special investigations
• Chest X-ray and thoracic CT scan may show an opacity in the lung and enlargement of the hilar lymph nodes. The differential diagnosis of a me- diastinal mass on radiological examination of the chest is listed in Box 10.1. There may be paralysis of one side of the diaphragm due to involvement of the phrenic nerve. In addition to imaging the chest, a CT scan should also image the liver and adrenal glands for evidence of secondary spread.
• A positron emission tomography (PET) scan is an invaluable means of both confirming likely malig- nancy in peripheral lesions and identifying medi- astinal spread. In conjunction with CT, it also per- mits resolution of, for instance, adrenal adenomas mimicking metastases.
• Bronchoscopy and biopsy. Bronchoscopy may reveal an ulcerating or exuberant growth, and involved lymph nodes may widen the carina.
Brushings and washings may be taken for cytology in addition to biopsy of a visible tumour.
• Fine-needle aspiration cytology of a peripherally placed lesion under X-ray guidance.
• Mediastinoscopy, performed through a small su- prasternal incision, may be indicated to remove
lymph nodes from the region of the carina for histological examination to aid in staging. Video- assisted thoracoscopic surgery (VATS) may also be helpful.
• Pulmonary function tests to determine lung re- serve and hence capacity to withstand surgery.
Chronic obstructive pulmonary disease is com- mon in this patient group. Patients with a forced expiratory volume in 1 second (FEV1) >2.5 litres can usually tolerate pneumonectomy; those with an FEV1 >1.1 litres can usually tolerate lobectomy.
This should be coupled with test of alveolar func- tion (gas transfer) and in surgical candidates, a prediction of remaining function with perfusion scan.
Treatment Surgery
Patients will come through thorough assessment in a multidisciplinary team (MDT) meeting. Surgery is undertaken in a subset of patients with sufficient respiratory reserve who have disease localized to one lobe or lung (T1, T2 or sometimes T3) but with only hilar (N1) lymphadenopathy. Mediastinal (N2) or more distal lymph node involvement is a strong marker of distal spread. For these patients, surgery alone has a poor outcome and must be linked with preoperative adjuvant chemotherapy.
Box 10.1 Abnormal shadow in the mediastinum
• Retrosternal thyroid
• Aneurysm of the thoracic aorta
• Thymic tumour and cysts
• Carcinoma of the lung with a mediastinal mass
• Heart enlargement: cardiac failure; valve incompetence; pericardial effusion; left–right shunts; cardiomyopathies
• Enlarged lymph nodes: sarcoid; Hodgkin’s disease;
non-Hodgkin’s lymphoma; leukaemia; secondary deposits
• Oesophageal enlargement: tumour; hiatus hernia;
mega-oesophagus in achalasia of the cardia
• Paravertebral abscess, particularly due to tuberculosis
• Scoliosis
• Dumb-bell tumour of neurofibroma
• Dermoid cyst or teratoma
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The aim of surgery is complete resection of the tumour and its related hilar nodes, together with ex- tensive sampling of all mediastinal node stations. For many patients, this will require lobectomy. Removal of the whole lung (pneumonectomy) is performed relatively rarely – it is a major physiological insult, with a mortality risk of at least 5%.
Many resections can be performed by minimally invasive VATS, as long as good oncological princi- ples of complete node clearance are adhered to. For patients with small tumours and limited reserve, segmental resections, following anatomical borders, give better long-term results than non-anatomical
‘wedge’ resections permitted by modern stapling instruments.
Radiotherapy
Radiotherapy may give useful palliation for inopera- ble cases. Although it may not prolong life, it may stop distressing haemoptysis, relieve the pain from bone secondaries and produce dramatic improvement in a patient with acute superior vena caval obstruction. It may also give some relief from the irritating cough and dyspnoea resulting from early bronchial obstruction.
Cytotoxic chemotherapy
Cyclical cytotoxic therapy combined with radio- therapy is the treatment of choice for small cell tu- mours. There is increasing evidence that regimens
combining cisplatin or carboplatin with etoposide, together with agents such as gemcitabine and pa- clitaxel for advanced disease, are also helpful in the treatment of resectable NSCLC with hilar (N1) dis- ease, given as neo-adjuvant therapy. It clearly has a role in unresectable non-small cell cancers, although the added survival is often disappointingly short.