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At the heart of general practice since 1960

Get set for a sharp rise in mesothelioma

One in 100 men born in the 1940s will die of

this asbestos-related disease ­ Dr Simon Swift and Professor Tom Treasure explain

diagnosis and treatment

In the 1960s mesothelioma was a rare disease with 100 or so cases a year. It is now 20

times more common. In the thoracic unit,

we are seeing new patients with this cancer every week.

In nearly all cases this cancer is a direct consequence of exposure to asbestos.

The relationship between causative agent and disease is tight, with asbestos exposure being almost an absolute requirement to develop the disease. Epidemiologists predicted the rise of this cancer nearly 10 years ago.

When the figures were re-analysed five years later the epidemic was very

much as expected ­ current estimates

suggest the annual number of UK mesothelioma deaths will peak at some

2,000 per year in about 10 years time, approximately 50 years after imports peaked (see graph on page 47)1,2.

The story in Europe is similar. The situation is better in the USA where asbestos imports were curtailed earlier. It is probably worse in Australia.

So we will be seeing steadily more of this disease, and as awareness increases we will see cases earlier and be expected to do more to help.

Objectives of care

Malignant pleural mesothelioma is a slow-growing cancer that starts in the parietal pleura, forming a thick cortex, and then encases the lung. It grows out, invading the chest wall. It often causes pleural effusion and two-three litres of fluid leaves little room to breathe. These changes cause the typical presenting features of worsening breathlessness and gnawing pain. It commonly presents late with a grim prognosis; survival from diagnosis is usually less than a year.

Even the best results with combined chemotherapy, surgery and radiotherapy are modest, and such trimodal therapy is only applicable to a few cases3. Of course, this has not stopped US surgeons advertising their wares on the web.

If a patient presents with chest wall pain and breathlessness the first objective is to make a diagnosis. If there is abnormality on the chest X-ray, fluid or pleural thickening, they should be referred to the chest clinic. Cytological examination of pleural fluid is the usual first step.

However, diagnosis of pleural disease may be elusive; a clear-cut positive gets you home in one test, but a negative result is of very low worth. A negative test in the face of symptoms and a grossly abnormal chest X-ray does not make the problem go away.

One of the worst things to do is to give false reassurance because the test is negative. We see patients who have been through months of this up and down of false hope and gloom. Where there is substantial suspicion, early referral is best: it enables a good volume of representative tissue for the pathologist and pleurodesis to keep the patient breathing as well as possible.

Investigations

The investigative algorithm starts with a CT scan followed by needle aspiration of fluid and either blind or image-guided pleural biopsy if pleural thickening is detected. Typical CT findings of mesothelioma include visceral and parietal thickening, which is commonly nodular with confluent growth into pulmonary fissures and diaphragmatic recesses, with chest wall invasion being a late sign. An effusion is often associated with reduced lung volume.

Pleural aspiration for cytology and symptom relief is a first step. Unfortunately a positive diagnosis is uncommon with diagnostic rates about 30 per cent. Blind biopsy similarly may yield a positive result, with diagnostic rates of 29-54 per cent. The biggest problem with the low diagnostic yield of these investigations is that a negative result is of no value and each puncture site may develop entry tract metastasis if the patient does have mesothelioma, causing painful lesions in 40 per cent of patients.

We recommend early referral to a thoracic surgeon for videoassisted thoracoscopic biopsy (VATS). This has a diagnostic rate of 90-100 per cent, as the surgeon can take multiple representative samples under vision. At the same time a talc pleurodesis can be performed for effusion, effectively palliating breathlessness without prejudice to further more aggressive treatment if appropriate.

Advising the worried patient

Perhaps one in 100 men born in the 1940s will die of mesothelioma3. This alarming statistic alone will bring patients to the GP's door. Patients frequently ask questions with no easy answers.

A history of asbestos exposure should be taken, but statistics don't always help in a consultation. Most deaths are in the very large number of people who had incidental exposure in ordinary building jobs or DIY. Wives and daughters who washed the overalls of asbestos workers are among those who have died. If the patient has symptoms these should be considered in the usual way by history and examination.

For a patient who wants to talk through worries, the charity Clydeside Action on Asbestos provides an excellent helpline (see box below). If the patient is very anxious and some action is warranted, a chest X-ray is the appropriate first step.

Patient's X-ray is normal The relationship between pleural plaques and disease is far from straightforward. Plaques are a sign of asbestos exposure, but they may be benign and a person can develop cancer without having them at all. So a negative X-ray does not mean there is no subclinical malignancy nor that the patient will not develop mesothelioma in the future. In most circumstances, beyond giving the good news it is best to not get into this discussion with the patient.

X-ray reveals abnormality This is now the domain of the chest physician. Either you are glad you did the X-ray because something treatable has been discovered, or you may have found benign asbestos plaques or some other abnormality which just keeps the anxiety going, but that's the way it is. This should be borne in mind before any investigation is considered.

Compensation for asbestos-related disease There are two routes to compensation: national compensation or by direct litigation against an employer. Neither is an easy path but expert help is available (see 'further information'). Histological proof and/or a post-mortem may be needed, but the best advice is to ensure the patient talks to a cancer nurse who knows the subject.

Surgical options

Definitive treatment once a diagnosis is reached depends on the cancer stage and the patient's fitness. Aggressive treatment is possible, with renewed interest in trimodal therapy combining pre-operative chemotherapy, radical surgery and post-operative radiotherapy. Case series show some long-term survivors, but we believe there is sufficient uncertainty whether this is due to surgery or nature and are running a clinical trial to find out.

Palliative treatment depends on the combination of symptoms and pathology for each individual and is a multidisciplinary task. The surgeon can control pleural effusion by talc pleurodesis. A patient is rarely too breathless for this; where the lung is 'trapped' ­ encased in inflexible tumour ­ symptomatic relief is less likely for a simple pleurodesis.

There is a local trial under way in Papworth of VATS decortication and pleurodesis for patients with trapped lung; there is little evidence available to comment on its outcome. Radiotherapy to puncture sites from aspiration, biopsy or VATS is effective in preventing port site metastasies and can be recommended on Grade A evidence4. The part chemotherapy has to play is also under trial (MSO-1) and the new drug pemetrexed (Alimta) has raised a lot of interest.

In those who are appropriate for radical treatment there is also a national trial. The Mesothelioma and Radical Surgery (MARS) trial has been funded by Cancer Research UK. It will test the trimodality package against multidisciplinary management without radical surgery. Recruitment starts in the next few months. If a patient is fit for radical surgery and initial staging indicates respectability, we are interested in hearing about them.

The procedure is similar in scope to pneumonectomy for lung cancer and carries similar risks in terms of mortality and morbidity, with a similar arduous recovery period. Postoperative radiotherapy to the empty hemithorax can be used at high dose levels.

A patient who completes all three arms of the treatment will have undergone a long and troublesome process about which specialists are either partisan or equivocal. It may, however, offer significant benefit. With an epidemic on the way only a trial can tell us.

Simon Swift is research registrar, thoracic surgery, and Tom Treasure is professor, Cardiothoracic Unit, Guy's Hospital, London

Further information

Clydeside Action on Asbestos offers free counselling and welfare rights advice, tel 0141 552 8852

UK Asbestos Action Group: www.hazardscampaign.org.uk/direct/dirp341.htm

References

1 Peto J et al. Continuing increase in mesothelioma mortality in Britain. Lancet 1995;345:535-9

2 Health and Safety Executive (2003), Mesothelioma Mortality in Great Briain: Estimating the Future Burden

www.hse.gov.uk/statistics/causdis/proj6801.pdf

3 Treasure T et al. Radical surgery for mesothelioma.

BMJ 2004;328:237-8

4 Boutin C et al. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma: a randomized trial of local radiotherapy. Chest 1995; 108:754-758

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