Lung Cancer

Professor Stephen Spiro, head of Respiratory Medicine at UCL, takes a close look at the different kinds of lung cancer and the latest techniques for tackling it...
"The lung is a 'silent' organ: it has no pain fibres. There may be no symptoms at all. So you may have no idea when something is wrong."
Approximately 35,000 people per year are diagnosed in the UK with lung cancer; of these 80 per cent are or were smokers. It is responsible for more deaths in the UK than any other cancer and remains one of the biggest challenges in tumour medicine worldwide, both in terms of developing better treatments as well as trying to change our social behaviour when it comes to smoking.

In the 1960s 65 per cent of men smoked; however, this has fallen dramatically to 22 per cent, which has resulted in a significant decrease in the number of lung cancers seen in men over the last 10 to 15 years. Indeed nowadays more ex-smokers are being diagnosed with lung cancer than current smokers, as it takes about 15 years from quitting for the risk to drop to that of someone who has never smoked. However, the number of women who smoke has remained constant at approximately 25 per cent of the adult population, with the greatest number of smokers aged between 15 and 25. It kills more women in this country than any other type of cancer, and of the 20 per cent of people who get lung cancer yet have never smoked, the majority are again women, although of a much younger average age than smoking-related sufferers. In the 1970s, when I first began treating lung cancer, I would see just one woman for every seven to eight men; this is now one woman for every two men, and approaching an equal-sex disease.
Signs & symptoms

Although all lung cancers begin within the substance of the lungs or in their airway tubes, the lung is a silent organ in that it has no pain fibres. If it becomes upset it may cause no symptoms at all, or just make you cough. You therefore have no idea when something is wrong. As a result tumours can grow quietly in the lungs reaching a large size, and more significantly, having time to develop metastases (secondary tumours). These can travel to the glands within the central tissues of your chest (mediastinum), as well as to sites outside the chest such as the brain, bones, liver, skin and other lymph glands. Coughing, or even a change in your cough, as many sufferers are smokers and will already have a bad cough due to co-existent chronic obstructive pulmonary disease (COPD). If this new or changed cough hasnt cleared within three weeks, your GP should arrange further investigations including a chest X-ray. Wheezing, especially if it seems to be coming from one lung, (due to an airway being narrowed by a tumour). A chest infection that fails to clear normally or returns within a couple of weeks. Coughing up blood is clearly an important symptom and should precipitate immediate investigations. However, reassuringly for most people who cough blood there is no sinister cause. Chest pain can herald lung cancer, due to the inflammation of the lining of the lung (pleurisy), or the spread of the tumour to the mediastinum, which often causes a central aching type of pain. Those who seem to fare best and can usually be treated by surgically removing the cancer are those whose tumour is often found by chance on a chest X-ray. So GPs should have a low threshold for getting this done in anyone at risk who has a new chest complaint.

Prevention

Prevention Clearly quitting smoking is extremely important and it is crucial to try to achieve this before the age of 40 years. After this age, the quantity smoked over the years adds up to a significant load, hugely increasing the risk of getting at least one, of all the smoking-related illnesses that abound. Screening for lung cancerLung cancer is the only common cancer that doesnt have a screening programme. There were efforts to see if a chest X-ray every year, or six months, in high-risk individuals would identify more lung cancers and thus save lives. Whilst this did seem to find more, often silent cancers, they were still not found early enough to affect the outcome and hence mortality rate was not improved. Current attention is now focussing on CT (computed tomography) scans, again in high-risk people – middle-aged smokers, often with COPD. The results of two large studies carried out over a three to five-year period, to see whether offering people an annual CT scan improves survival rates, are being awaited. However, current evidence shows that radiological imaging will still not detect lung cancer early enough to make a difference.

Types

There are two major types of lung cancer: Small cell which makes up between 15 and 20 per cent of all cases. This is entirely smoking related and is the most aggressive cell type. It is usually too advanced for surgical removal and best treated by chemotherapy and possibly radiotherapy as well, depending on how localised it is when treatment is planned. Non-small cell lung cancers (NSCLC). This is the largest group and comprises different cell types: About 35 to 40 per cent are squamous cell. Again, this is almost entirely caused by smoking. However, it is the cell type least able to spread, which means it can often be treated with surgery, and has the highest cure rate. Adenocarcinomas are both smoking and non-smoking related cancers. They may spread, but are best treated whenever possible by surgery. This is the commonest type of lung cancer worldwide, and accounts for approximately 30 per cent of lung cancers in the UK.

Treatment
  • Surgery: Whenever possible lung cancers should be treated surgically, either by cutting out a lung lobe (lobectomy), or by removing the whole lung (pneumonectomy). The latter however is only done occasionally, as it can only be carried out in fitter individuals, those with excellent lung function and able to cope with just one lung, without being rendered impossibly breathless for day-to-day activities. As mentioned above small cell cancers are only very occasionally suitable for surgery, because the disease has spread beyond the lung at diagnosis. With NSCLC, only about 10 to 25 per cent are operated on because when they present, they appear confined to the lung. These cases all undergo extensive staging tests, including a CT scan and also a PET scan, or a combination of PET and CT, as well as careful lung function testing to make sure surgery will be withstood. Sadly because modern staging still only identifies metastases of 7mm diameter or more, some patients thought to have had a successfully curative operation will die of their cancer within the following five years due to silent, tiny metastases continuing to grow after surgery.
  • Radiotherapy: When it comes to lung cancer the main role of radiotherapy is controlling the symptoms in people with advanced disease. For example, it can stop the coughing up of blood, shrink the tumour to improve breathlessness, relieve pain in bones, and control metastases in the brain or spinal cord. However, there are often people with technically removable tumours, but for whom surgery would be too dangerous, perhaps because their lung function is too poor, or they are too old to undergo thoracic operations. For them radiotherapy can be given with curative intent, and on the whole is 50 per cent as effective as surgery in getting a cure. The lung does not tolerate radiotherapy well above a certain level. However, because techniques are improving all the time, with equipment able to focus the treatment beam with ever-increasing precision, higher doses can now be focussed on the tumour whilst sparing the surrounding lung; this improved intensity of therapy may also improve survival following radiotherapy.
  • Chemotherapy: In the management of small cell lung cancer, chemotherapy is the mainstay. As the tumour is aggressive, many cells are in division and therefore susceptible to chemotherapy. Usually four to six courses of intravenous chemotherapy are given, one course every three weeks, so it is usually well tolerated and, in small cell, very effective. In about 50 per cent of cases the disease will disappear from X-rays and scans, but sadly after a period of good health and remission, it can come back and is then resistant to most treatments. Radiotherapy will consolidate the gains of chemotherapy and is often given on completion. All in all about five per cent of people with small cell lung cancer are cured, and still fit and well after five years. With NSCLC, 80 per cent of cases cannot be treated using surgery or radiotherapy because the disease is too far advanced. Likewise with chemotherapy, some people are just too unwell to face it, others too old or frail or both. Also NSCLC is much less aggressive than small cell and therefore the response to chemotherapy is less dramatic and very few cases see the tumour disappear from view. However, for those who are still pretty fit, chemotherapy has seen some real advances over the last 15 years. It rarely cures, but has trebled the life expectancy of many patients.
'The whole arena of systemic treatment for advanced NSCLC is a rapidly changing field and more advances are expected in the near future'
In the past, research showed no real differences between regimes of chemotherapy drugs, and hence the emphasis was on using the least upsetting combinations with the fewest side effects. However, we now have different drugs for different cell types, which means its extremely important to get a precise diagnosis so that the right choices can be made. Furthermore, immunohistochemistry, which identifies tumour antibodies within the tissue samples taken for diagnosis, has added a further measure of diagnostic certainty, and is performed as a routine. Also the genetics of lung cancer are better understood with different mutations rendering an individual tumour less, or more susceptible to specific targeted treatments. Today, the treatment for squamous cell tumours involves using different drugs to those used to treat adenocarcinomas, and these differ from the choices in small cell cancers. The correct choice makes a significant difference as to the patients outcome. Similarly looking for certain mutations allows the oncologists to decide if a targeted drug would be a better choice than chemotherapy, or often as a second line treatment instead of further types of chemotherapy. For example, women who were never smokers, with an adenocarcinoma of the lung and of Asian origin will do extraordinarily better on targeted therapy, usually a tablet treatment, than with chemotherapy. 

The whole arena of systemic treatment for advanced NSCLC is a rapidly changing field and more advances are expected in the near future. However, treatment remains difficult as patients are still facing the inevitable that, for many, the illness will be fatal. It is also harder to treat elderly patients who suffer from lung cancer, as they tolerate chemotherapy less well than their younger counterparts. The average age of lung cancer at diagnosis in the UK is nearly 70 years, and many people of this age dont want or cannot tolerate tough treatments. Also, the majority of those who get lung cancer are often not health conscious: they are smokers or ex-smokers, have already taken risks as a result, are older and usually of a lower socio-economic status. All this, plus the fact that they often have other illnesses, or are single, bereaved, or live alone, makes the facing up to their illness too difficult. Much of the treatment for lung cancer is palliative and the lung cancer nurse, the palliative care nurse, the hospice nurses and doctors, as well as the GP, will have a huge role in getting the best quality of life for each individual as the disease progresses. However, there is currently great interest in research for lung cancer – for screening and for new treatments. Bearing in mind the number of people who have or will get this dreadful illness, progress is much needed and the research community is responding well to the challenge.