Lung Cancer
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.
Classification
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.
Presentation
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
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.
