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04 February 2011

Lung Cancer

Lung cancer is also known as bronchial carcinoma, because the majority of tumours originate from the bronchial walls.

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Alternative names

Bronchial carcinoma

Description

Lung cancer is also known as bronchial carcinoma, due to the tendency of the majority of tumours to originate from the bronchial walls. The bronchial walls are rare sites in the body, in direct contact with our immediate environment and inhaled carcinogens, and this can subsequently impact directly on the bronchial walls and contribute to enhancing local tumour growth.

Bronchial carcinoma is the most common solid tumour growth in men, and in women has surpassed breast cancer as the most common tumour of females in several developed countries such as the United States of America. The prevalence of the disease has plateaued in men in developed countries, but has maintained an alarming rise among women due to an increasing tendency for young girls and adult women to take up smoking.

The bad prognosis for which the disease is known relates to its silent onset and capacity to spread beyond the confines of the lungs before it becomes symptomatic and can be detected.

Types

Bronchial carcinoma is divided into two main categories based on prognosis and treatment: small cell carcinoma, which has a very bad prognosis, and non-small cell carcinoma, which has a better prognosis.

Small cell carcinoma

Small cell carcinoma is a tumour that usually originates centrally in the lung and has a clear relationship to cigarette smoking. This carcinoma has a particularly bad prognostic significance because it usually metastasises (spreads) to distant organs such as the adrenal glands, brain, bone or lymph nodes before the initial diagnosis can be established. Due to its malignant nature it is not operable, but an initial respite of several months can be gained by chemo- and radiotherapy.

Non-small cell carcinoma

There at least four subtypes of non-small cell carcinomas, including:

  • Squamous carcinoma, which accounts for 40-60% of bronchial carcinomas. Squamous carcinoma is related to cigarette smoking and can be resected surgically. The surgery involves removing the part of the lung with the tumour - if detected at an early stage of its growth.
  • Adenocarcinoma, which occurs in the periphery of the lung, tends to follow a silent course and metastasises to the brain before patients report symptoms. If detected at early stage, this tumour can be surgically resected.
  • Two other tumours known as large cell carcinoma and bronchiolo-alveolar carcinoma fortunately occur in a minority of patients as both these tumours have a particularly dismal outcome.

It should be noted that the lungs are frequently affected by metastatic tumours from other organs, which represent radiologically as round lesions and are subsequently referred to as "cannonball lesions" by radiologists.

A rational approach to the treatment of bronchial carcinoma can only be achieved by cellular or tissue classification of tumours.

Diagnostic procedures and staging

Procedures for obtaining small tissue samples on which the classification of tumours can be done include needle aspiration, sputum cytology and bronchoscopy – a procedure whereby an instrument with a lens at its tip is placed through the vocal cords into the bronchial tree. Small tissue samples can be obtained under direct vision.

Due to the severe prognostic implications of this disease, patients should not be confronted with the diagnoses before confirmation on tissue or cell samples is finalised.

Once a histological or cytological diagnosis has been made, a process called "staging" occurs, during which the location and size of the tumour in the lungs is determined. Evidence of infiltration of adjacent structures, involvement of regional lymph nodes and distant metastases are considered. This approach enables the treating physician and onchotherapist (tumour specialist) to plan the best therapeutic approach with the lowest side-effect to therapeutic ratio for patients (see management of bronchial carcinoma).

Early diagnostic procedures in symptomatic individuals, conducted by radiologists, pulmonologists and thoracic surgeons, who in turn would have been alerted by the general practitioner, is the most effective means of combating this disease. Treatment of advanced disease is frequently only palliative and not curative.

Cause

The relationship between tobacco smoking and bronchial carcinoma has been established beyond all doubt. An association between smoking of cigarettes and bronchial carcinoma has been established in up to 90% of male and 80% of female smokers. Bronchial carcinoma rarely occurs in non-smokers.

Factors that increase the prevalence of cancer in smokers include starting smoking at an early age, and a high number of cigarettes smoked per day. In these individuals the total load of carcinogens, which could include inorganic substances such as arsenic and nickel as well as other organic substances, will after years of chronic pollution of the airways eventually give rise to pre-cancerous changes in cells. These changes occur as a result of the carcinogens penetrating the DNA of bronchial wall calls. Subsequently the orderly subdivision of cells changes into an uncontrolled growth of tumour at one or more sites in the bronchial walls.

Cigarettes with filter tips, and discarding half-smoked cigarettes may prevent the early onset of bronchial carcinoma, but are by no means protective. Pipe and cigar smoking have a lower prevalence of bronchial carcinoma, but lose this halo of innocence through a higher prevalence of lip, larynx and oesophagus carcinoma.

The danger of secondary or side-stream cigarette smoke as a cause of bronchial carcinoma has been well established in studies of non-smoking spouses of heavy smokers as well as in non-smokers exposed to smoking in the workplace. Forced or passive smokers inhale particularly high concentrations of carcinogens from side- stream smoke, but the prevalence of bronchial carcinoma is still lower in these unfortunate individuals compared to smokers.

In previous light smokers who stop smoking, the tendency to bronchial carcinoma declines after 10 years to that of non-smokers, but in previous heavy smokers only to two and a half times less than that of current smokers.

Exposure to dust and gas exposure in industry is a powerful inducer of bronchial carcinoma. The list of dangerous inhaled substances includes asbestos, which, in addition to asbestosis, can cause mesothelioma (cancer of the lining of the lung, the pleura) and also a bronchial carcinoma. Whereas unfortunate non-smokers do develop mesothelioma due to exposure to asbestos, dust bronchial carcinoma hardly ever occurs in non-smoking asbestos mines. Smokers exposed to asbestos dust have nine times the risk of non-exposed smokers and 92 times the risk of non-exposed non-smokers for developing bronchial carcinoma.

Bronchial carcinoma in mining has also been related to radioactivity emanating from the underground environment and subsequently from dust in uranium, fluorspar and even in iron-ore mines. Radioactive dust contains a-particles and radon daughter substances, which have a high capacity to change DNA structure and over the years contribute to the onset of bronchial carcinoma. A strong compounding effect of cigarette smoking and the onset of bronchial carcinoma in workers in these mines has also been established.

Other industrial substances such as nickel, chromium salts and arsenic used in metal refining and the chemical industry have also been proven to be carcinogenic.

A genetic tendency to the development of bronchial carcinoma, although difficult to quantitate, will undoubtedly make a contribution to the onset of the disease in a small group of individuals who have a bad family history of all types of cancer.

Atmospheric pollution, although undoubtedly relevant to the onset of chronic obstructive pulmonary disease and the worsening of asthma, has not been shown beyond all doubt to be a factor of importance in onset of bronchial carcinoma.

Presentation

The silent onset of the disease, as well as the fact that atypical symptoms may occur, defies an early diagnosis in most patients with lung cancer. Calculated on the doubling time of tumours, patients can have squamous carcinoma for up to two to three years and adenocarcinoma in excess of 10 years before symptoms develop.

Chance detection of bronchial carcinoma through chest x-rays taken for other reasons frequently present early evidence of lung tumours. Bronchial carcinoma causes symptoms through one of three mechanisms:

  • local manifestations
  • metastatic manifestation
  • non-metastatic systemic manifestations.

Local manifestations include symptoms of cough and sputum production due to the intrabronchial protrusion of the tumour. This lesion may change the character of sound in chronic coughers to a “brassy” sound. Obstruction of normal sputum flow and subsequent recurrent chest infections may manifest as recurrent attacks of bronchitis, pneumonia or lung abscesses. These manifestations should alert patients and attending physicians to obtaining an chest x-ray, particularly in smokers older than 40 years.

The development of haemoptysis, or coughing of blood due to erosion of a vessel of the bronchial wall by a tumour, causes predictable patient concern. Tumours that haemorrhage can usually be visualised by bronchoscopy and this investigation becomes essential when an abnormal x-ray indicates a mass or collapse of a lobe due to bronchial obstruction. Large centrally located masses usually cause obstruction of major airways with subsequent collapse of one or more lobes or a whole lung. These patients will complain of increased shortness of breath or a wheeze, which does not respond to normal bronchodilatory treatment.

Patients report pain when the cancer has infiltrated chest structures such as bones of the thoracic (chest) wall, and nerves located above the apex of the lung.

Infiltration of the pleura (a thin lining of cells covering the lung surface and the inside of the chest wall) can cause pain during inspiration. When large amounts of fluid accumulate in the pleural space, the pain will be dampened, but pressure on the underlying lung causes shortness of breath. Experienced physicians will on examination of the chest be able to identify the presence of pleural effusions in the pleural cavity, lung collapse or even partial obstruction of major airways.

Evidence of metastases from lung tumours, in distant organs such as the brain, bone involvement with fractures and bone pain, and frequent silent peripheral organ involvement, may only be detected by investigative techniques.

It is of utmost importance that patients at risk, particularly those older than 40 years, should consult their general practitioner or pulmonologist whenever new symptoms arise for which no obvious explanation can be found. Subtle symptoms such as weight loss, loss of appetite, unexplained anaemia and a chronic feeling of ill-health should alert smokers to the need to obtain a professional opinion. No evidence has been found that regular annual clinical and radiological evaluation of healthy individuals can prevent the high mortality and morbidity through early diagnosis of the disease. The cost involved in this approach compared to the positive yield has also been found to be prohibitive.

Treatment

It should be evident that curative treatment of bronchial carcinoma depends on the type of cancer as well as how far the disease has spread at the time of diagnosis.

Surgery

Removal of an affected lobe (lobectomy) or a whole lung (pneumonectomy), with the corresponding lymph nodes if required, represents the only curative form of treatment for bronchial carcinoma. Due to frequent distant spread of the disease by the time of diagnosis, this option is available in less than 15% of patients, while in countries with a predominant Third World population, the figure for operability declines to as low as 5% of patients at diagnosis.

Pre-operative evaluation of patients by pulmonologists and thoracic surgeons using techniques such radiography, bronchoscopy and cytology is conducted to classify patients in a tumour/node/metastasis system. By selecting patients who have localised disease and by planning their operation to ensure that patients of all ages are generally fit enough with adequate residual lung function, post-operative survival with a good quality of life can be ensured. Lack of pre-operative evaluation, surgical and post-operative support facilities decreases the number of five-year survivors to less than 5% in developing countries.

Radiation therapy

Radiation treatment of bronchial carcinoma is an option usually reserved for patients who are inoperable. This highly sophisticated form of treatment has to be planned by a team consisting of physicians and radiotherapists. Although isolated cases of cure after radiotherapy have been recorded, the main object is that of palliation (alleviation) through shrinkage of the tumour and relief of symptoms such as pain and haemorrhage.

Certain types of tumour such as adenocarcinoma are not amenable to radiation therapy, while others such as small cell carcinoma show an immediate but not sustained response to this form of treatment. Extensive radiotherapy, which is planned and conducted to secure optimal survival for patients, can have immediate and medium-term unpleasant side-effects. Palliative irradiation of the primary tumour and its metastases in bone and the brain usually provides immediate but short-term relief of symptoms, and allows patients and their families several weeks to months to finalise essential matters.

Chemotherapy

The success of chemotherapy as a form of palliative treatment depends on the type of tumour, the funds available to afford this expensive form of treatment, and the general viability of patients. The side-effects of this type of treatment are notorious, but supportive medication and better selection of chemotherapeutic agents have improved the quality of life of patients during and after this mode of treatment. No single chemotherapeutic agent has been found effective and combination treatment with a number of drugs is usually administered.

Once again, the small cell carcinoma group responds temporarily to this form of treatment, whereas the other types of tumour generally do not respond well to chemotherapy.

Combination treatment

Pre- and post-operative irradiation and chemotherapy have been utilised in recent years in an attempt to shrink the tumour and limit local infiltration before surgery or as a “mop-up” treatment post-operatively, particular when the surgeon has found more extensive disease than predicted.

The limited survival period of patients with bronchial carcinoma should be respected. Despite good intentions, no treatment should be planned that severely reduces the quality of life, which these patients may enjoy for a limited period of time. Support of family and friends and home care by Hospice and other professional organisations should not be underrated, as their support and palliation carry patients through the final days and weeks when medical science has acknowledged defeat.

Bronchial carcinoma has stubbornly resisted every research and scientific approach to improve its dismal outcome. On the brighter side, hope lies in educating the public so that informed decisions as regards to smoking will be made in future, which will lead to a decline in the prevalence of the disease.

No stronger message can be conveyed to the youth than to abstain from smoking, as this condition represents one of a number of diseases with a fatal outcome from which long-term smokers will rarely escape.

Reviewed by Dr Greg Hart, Oncologist, GVI Oncologies at the Vincent Palotti Oncology Unit, Vincent Palotti Hospital (April 2010)

 
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