More people die in the USA and Europe from lung cancer than from breast, prostate and colon cancer combined. Furthermore, the number of cases is likely to increase in the next 25 years due to continued use of cigarettes, particularly in women. Lung cancer has a worse prognosis than other common cancers, with an overall 5-year survival of 13%.
Cigarette smoking accounts for the vast majority of lung cancer cases. Risk is directly related to the duration and number of cigarettes smoked, age of initiation, depth of inhalation and levels of tar and nicotine. In heavy smokers (>20 packs/years) the lifetime risk of lung cancer is 10%, 10-30 times greater than for lifelong non-smokers (<0.3%). After quitting cigarettes, risk gradually declines over 15 years, but remains 2-5 times greater than in non-smokers. Passive smoking in non-smokers may increase the risk by approximately 1.5%.
Asbestos exposure is the most common occupational risk for lung cancer (Chapter 33). Tobacco smoke is synergistic with asbestosis, increasing the relative risk to 6-60 times that of a non-smoker. Radon gas, found naturally in rocks, soil and ground water, may also increase risk.
Lung cancers are divided pathologically into small cell (SC, 20-30% of total) and non-small cell (NSC, 70-80% of total) types. NSC types are grouped due to their similar biology, treatment and prognosis, and include squamous cells (30%), large cells (15%) and adenocarcinoma (33%), which are increasing in prevalence, especially in women. Adenocarcinomas typically present as a peripheral nodule (<3 cm) or mass (>3 cm); they are the most common type in non-smokers, and mainly arise in areas of pulmonary scarring. Bronchoalveolar cell carcinoma is an adenocarcinoma variant with low metastatic potential. Squamous cell carcinomas arise from the bronchial epithelium, and generally present as a central mass with tumour visible in the airway (Fig. 40a and b), often with symptoms due to local tumour invasion (cough, haemoptysis, chest pain and hoarseness). Large cell carcinoma is undifferentiated, and lacks the histological features of adenocarcinoma or squamous cell carcinoma; it generally presents as a large peripheral mass, often with metastases. SC carcinomas arise from neuroendocrine cells in the bronchial submucosa, and typically present as a central mass with lymph node enlargement. These are ag- gressive tumours that invade lymphatics and blood vessels. Nearly all have metastasized at diagnosis.
Less than 10% of lung cancers are discovered incidentally in asymp- tomatic patients. Most patients are 50-70 years of age, with non-specifi symptoms including new unresolving cough, haemoptysis, chest pain, hoarseness, dyspnoea on exertion, malaise and weight loss. Symptoms due to haematogenous extrathoracic metastasis to bone, liver, bone marrow, adrenals and brain are present in around one-third of patients at diagnosis.
Paraneoplastic syndromes - signs or symptoms associated with lung cancers that are not related directly to metastatic tumour may precede radiographical demonstration. They may be due to secretion of hormones or hormone-like substances from tumours, or serum autoantibodies (e.g. anti-Hu) related to tumour antigens. SC carcinoma is associated with most paraneoplastic syndromes including Cushing's syndrome, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), Lambert-Eaton syndrome, cerebellar ataxia or idiopathic orthostatic hypotension. Squamous cell cancer may cause hypercalcaemia from release of parathyroid hormone-related peptide.
Physical finding in the lung are related to disease extent. Small parenchymal nodules are undetectable by physical examination. Focal finding may be due to atelectasis, airway invasion, pleural ef- fusion (Chapter 32) or supraclavicular adenopathy. Invasion of adjacent structures may cause superior vena cava syndrome (obstruction), Horner's syndrome (autonomic overactivity) or brachial plexopathy. Digital clubbing or hypertrophic pulmonary osteoarthropathy may be present.
Evaluation of patients with suspected lung cancer should include demonstration of malignancy, staging and suitability for therapy. Radiographs provide information regarding the size and location of the tumour, benign calcification involvement of adjacent structures, atelectasis, pleural effusion and adenopathy (Fig. 40c). Computed tomography (CT) scans are superior to plain X-rays. If a focal lesion does not change in 2 years, it is unlikely to be malignant. Positron emission tomography (PET) scanning has a high sensitivity for distinguishing benign from malignant nodules and for detecting nodal or distant metastases.
Staging is assessment of the extent of the tumour, and largely determines treatment options and prognosis. Separate staging systems are used for SC and NSC cancers. SC cancer is staged as either limited or extensive disease. Limited disease describes tumour confine to one hemithorax, including malignant pleural effusion and supraclavicular lymph node metastasis. Extensive disease describes metastatic spread beyond the hemithorax. SC cancer is generally an incurable disease. Standard therapy for limited disease (33%) is combination of chemotherapy and radiotherapy, with response rates approaching 90%; median survival with therapy is approximately 18 months. Standard therapy for extensive disease (66%) is chemotherapy. The response rate is approximately 70%, treatment prolonging median survival from approximately 3 months to approximately 1 year.
NSC cancer staging is based on the tumour (T), node (N) and metastasis (M) classificatio system (Fig. 40d). T3 tumours invade thoracic structures that are potentially resectable, and T4 tumours in- clude malignant effusions or tumours invading non-resectable struc- tures. Summation of TNM categories determines the stage of disease and treatment, and predicts survival (Fig. 40e). In functional patients with stage I or II disease and adequate pulmonary reserve (postoperative FEV1 >800 mL), surgical resection is optimal. Some patients with stage IIIA disease are surgical candidates. Patients with stage IIIB or IV disease are not candidates for curative resection. Unresectable dis- ease is generally treated with chemotherapy and radiation therapy, or radiation alone. Stage IV disease is incurable (median survival 6-12 months). Treatment options are palliative. Painful bone metastases, brain metastasis or airway obstruction may improve with directed therapy. The benefi of aggressive chemotherapy for patients with advanced disease is modest. Platinum and taxol-based chemotherapy regimens are currently most common for NSC cancer.