There are several types of lung cancer, distinguished by the appearance under the microscope. The two main types are non small cell lung cancer and small cell lung cancer. The sub type of small cell lung cancer is important to recognise separately as the as the management of this condition differs from its more common counterpart, non small cell lung cancer.
Non small cell lung cancer consists of different sub types including squamous cell carcinoma, adenocarcinoma, a combination of adeno and squamous carcinoma, large cell carcinoma. There are rare types of primary lung cancer including giant cell carcinoma and bronchial alveolar lung cell carcinoma.
Many cancers arising from other organs of the body can spread to the lung (lung metastases) and it is important to differentiate these from a primary lung cancer which has arisen from within the lung as the management would be dictated by organ from which they have arisen.
Causes of lung cancer
The rise in lung cancer mortality during the twentieth century was statistically linked with the increase in smoking. On cessation of smoking, the risk falls but remains above that of the background population even after 15 years.
Further factors that may increase the chance of developing lung cancer include ionizing radiation, occupational exposure to carcinogens such as asbestos, arsenic, chromium. There is renewed interest in the familiar inheritance of lung cancer.
Symptoms of lung cancer
Early lung cancer may not cause symptoms. For patients with symptoms of lung cancer may be due to the local development of the tumour in the lung or from the spread of the disease. Local symptoms include a cough that may persist, breathlessness, chest pain, coughing up blood, a hoarse voice, and recurrent infections of the chest.
General symptoms include fatigue, weight loss, burning pain from metastatic spread or symptoms from spread to other organs e.g. headaches from brain metastases
Diagnosis of lung cancer
The doctor first performs a chest x-ray and if this shows anything suspicious he will run a CT scan of the chest. The analysis of the sputum for abnormal cells is the next test (sputum cytology) and is a very accurate diagnostic tool if positive, and this is usually the case if the patient is coughing up blood; it is less often positive otherwise.
If the tumour is not diagnosed by the sputum cytology, the doctor orders a bronchoscopy (a test where a telescope is manipulated down the throat into the wind-pipe (the trachea) and into the bronchial tubes to directly see any tumour arising from the walls of these tubes.
It is worth noting here that almost all lung cancers are bronchial cancers and arise from the walls of these bronchi. When the tumour is seen or an abnormal area discovered at bronchoscopy, the doctor will take a piece of tissue (biopsy) from this area for subsequent analysis down the microscope for a certain/pathological diagnosis.
If the tumour is not easily seen down the bronchoscope and a single lung shadow on the x-ray could be a birthmark (hamartoma etc.) then a PET scan is useful. This is a functional scan which is ‘hot’ when there is tumour there in the lung but ‘cold’ when the chest x-ray abnormality is one of any of the lung benign shadows which include congenital hamartomas or scars from old injury. If the result is equivocal or PET scan positive and the lesion not able to be biopsied on bronchoscopy, then a transthoracic fine needle biopsy directed by CT is diagnostic in most cases.
The message from all the above is that the diagnosis of lung cancer has to be made from sputum cytology or biopsy (which is down the microscope). Sometimes the patient presents with spread of the cancer outside the chest and then the diagnosis can be made from biopsy of a metastasis, e.g. an abnormal lymph node in the neck.
Treatment of lung cancer
Surgery is recommended for early stage disease. This applies to stages 1-2 and may apply selectively to stage 3 of the disease. Before operating on an early stage non-small cell lung cancer, the surgeon will take matters other than the fact that the disease is early on staging into account. This will depend on the size and situation of the cancer. He will want to know that the patient's lung function, which is often impaired due to a lifetime of smoking, can withstand the loss of lung tissue that will result. This lung ‘reserve’ can now be adequately assessed before any planned operation nowadays, and must be known to the surgeon prior to the planned operation. Similarly, the patient’s heart must be in good enough shape for operation.
Thus, after the staging of the disease as outlined above and the pre-operative medical assessment, the patients who ‘qualify’ proceed to lung resection (either lobectomy - lobe removal or pneumonectomy - removal of the whole lung) at a chest splitting operation called a thoracotomy. At operation, the surgeon will re-assess the situation. If the disease is actually more extensive within the chest than the scans regarded it to be (and this happens despite the most careful pre-operative assessment, then there is no advantage in proceeding to major lung surgery without the possibility of removing all the disease and the surgeon will close the chest without having carried out a definitive operation.
Where the disease is confined to the lung or the stage 2 disease that the pre-operative imaging defined, the resection proceeds as planned. In selected patients, there is a marginal benefit in consideration of chemotherapy following surgery. This would need a detailed discussion with the oncologist as the balance of side effects against the benefits need to be carefully appraised.
There is still no consensus as to the place of radical surgical resection, as just outlined, where there is early central chest/mediastinal lymph nodal disease on the pre-operative staging, and the early stage 3 patient may additionally gain advantage from chemotherapy and mediastinal radiotherapy. There are many clinical trials currently underway trying to sort out the use of radical surgery plus chemo- and/or radiotherapy in stage 3 disease.
Radical (this term refers to therapy given with curative intent) radiotherapy is given to patients with stage 1 and 2 disease where surgery is contraindicated on medical grounds or the patient declines operation.
The radiotherapy is given via high energy linear accelerators and using conformational techniques to mould the high dose therapy around the primary tumour in the lung and its immediate draining lymph nodes at the root of the lung, whilst minimising the dose to the normal lung tissue. The patients undergoing radical radiotherapy attend a Radiotherapy Department from three to six weeks depending on the type of radiotherapy prescribed. In general, a course of radiotherapy may be given on weekdays over 6 weeks. In some centres, treatment may be given up to 3 times a day including weekends over a period of 3 weeks.
A proportion of patients will have advanced disease that is not amenable to cure. The management options in these patients include surveillance until there is symptomatic progression of disease, chemotherapy treatment to prevent progression of disease and palliative treatment with radiotherapy for local symptoms such as chest pain or a persistent cough due to tumour. Chemotherapy drugs continue to evolve and the newer combinations are generally well tolerated with improvements in symptom control and some improvement in survival. Newer agents including biological drugs that can disrupt blood vessel formation and drugs which identify certain receptors on cancer cells have also proven of benefit and can be added to chemotherapy regimens.
In spite of advance in lung cancer treatments, the outlook remains poor. Studies or clinical trials are underway to assess the benefit of chemotherapy prior to surgery, the combination of chemotherapy and biological drugs given in conjunction with radiotherapy, and the extended use of these drugs after surgery or a course of radiation.
Small cell lung cancer
Small cell lung cancer has a much higher predisposition to spread/metastasise to other organs early in its natural history and it is for this reason that it is very rare that surgery is ever thought appropriate for this disease:
Fit patients with limited stage disease should be considered for a combination of chemotherapy and radiotherapy treatment. Chemotherapy is administered at the start of radiotherapy but is some cases can precede the radiotherapy treatment. Radiotherapy may be given twice daily over a period of 3 weeks or once daily over a period of 5 weeks. A proportion of patients with small cell lung cancer relapse with brain metastases. The addition of radiotherapy to the brain during or after the course of lung radiotherapy has been shown to reduce the rate of brain metastases (prophylactic cranial irradiation).
In patients with extensive stage small cell lung cancer the treatment intent is palliative. Chemotherapy can reduce the tumour burden in fitter patients. Local palliative radiotherapy can reduce symptoms from metastatic disease e.g. bone pain, brain metastases. Surveillance with symptom control should be considered for those patients who are frail and not fit to tolerate more aggressive therapies.