The epidemic is still to peak and we need more research to manage it

Editorial

http://bmj.bmjjournals.com/cgi/content/full/328/7434/237

One in every hundred men born in the 1940s will die of die of malignant pleural mesothelioma, which is almost exclusively a consequence of exposure to asbestos, with a lag time that is rarely less than 25 years and often more than 50 years from first exposure. Half of all cases are now aged over 70, with 80% in men. For a man first exposed as a teenager, who remained in a high risk occupation, such as insulation, throughout his working life, the lifetime risk of mesothelioma can be as high as one in five.^w1 There are now over 1800 deaths per year in Britain (about one in 200 of all deaths in men and one in 1500 in women), and the number is still increasing.^{1 w2} As exposure in the United Kingdom continued until 1980 the peak of the epidemic is still to come, and we need a strategy to manage these patients.

Asbestos was a valuable and versatile material and imports rose after the second world war when it was widely used as an insulator, in the manufacture of filters, cements, friction products, and as a fire retardant. It found a place in shipbuilding and industry and was used extensively in building in the form of light workable boards.² It was a convenient partitioning material that combined insulation and fire proofing. The Health and Safety Executive statistics indicate that 25% of deaths will be in men who worked in the building industry and that carpenters and joiners are most commonly afflicted.^w3 These men have often been self employed in small enterprises or engaged in do it yourself home improvements. About 90% of deaths due to mesothelioma are due to exposure to asbestos in unmonitored settings. Wives and daughters who washed the overalls of asbestos workers are among those who have died.

Imports were at their highest from about 1955 to 1980 in the UK.³ The Asbestos Licensing Regulations came into force in the United Kingdom in 1983 and Control of Asbestos at Work Regulations in 1987 (both amended in 1988). The peak of the epidemic is expected in 2015 to 2020 when the death rate is likely to be 2000 per year in the United Kingdom. The situation in Europe is similar.⁴ Australia had the highest pro rata asbestos usage,^w4 and asbestos imports continue in the developing world.^w5 The epidemic in the United States has probably peaked because of earlier awareness and action on asbestos imports.⁵ Many countries are seeing the rising tide of an epidemic, and all doctors need to know how to recognise and diagnose this disease and what treatments are available.⁶

Mesothelioma is a relatively slow growing tumour that most commonly originates in the parietal pleura but can also arise in the abdomen and the tunica vaginalis. It presents with pain in the chest wall or breathlessness due to increased pleural fluid, but symptoms may be absent or develop insidiously. Not infrequently, at the time of first awareness, a thick rim (1 cm or more) of hard dense tumour encasing and restricting the lung may already be present. The diagnosis can be difficult to prove. When pleural disease is found it has to be distinguished from pleural plaques and malignant effusion from adenocarcinoma.⁶ Cytological examination of pleural fluid and small needle biopsies are often inconclusive because adequate tissue is required and it may take several attempts, culminating in surgical biopsy—each time with a risk of infection and needle or drain track seeding to which mesothelioma is particularly prone. Biopsy and drain tract radiotherapy is recommended.⁶

Once made there is tendency for the diagnosis to be met with a sense of hopelessness—not without good reason for it is a horrible disease, often with months of unremitting pain, progressively diminishing pulmonary performance, cachexia, and the inevitability of death. Median survival from diagnosis is usually under a year, but individual series vary markedly^{7 8} as is not surprising in a cancer with such a long lead time and in which the known phase of the disease is a small proportion of its natural history.

How can we think about it positively? The best we can offer at present is stage specific treatments, which should whenever possible be within clinical trials.

As with most solid tumours the first consideration is surgery—can we cut it out and get rid of it? The operation, extrapleural pneumonectomy, entails removal of all the parietal pleura, the pericardium, and the diaphragm in addition to the whole lung on that side.⁹ It is usually considered as part of trimodality treatment with various combinations of preoperative and postoperative chemotherapy and radiotherapy to the empty hemithorax after surgery.¹⁰ This is associated with survival figures of up to 48% at five years in highly selected subsets of patients with the more favourable epithelioid (as opposed to sarcomatoid) histology and no lymph node metastases.^w6-w9 Radical surgery has been performed infrequently in the United Kingdom, with an average of only 20 patients per year in the past five years. Some patients and their doctors desperately seek radical surgery as their only hope, but others have doubts about the evidence.¹¹ A trial is needed, and a pilot feasibility study (the mesothelioma and radical surgery "MARS" trial, funded by Cancer Research UK) is now under way. To answer the question 670 patients will be required over three years with five years' follow up. If achieved this would give an answer by about 2012 in time for the peak of the epidemic.

Irrespective of whether radical surgery will be considered much needs to be done in the care of these patients. The diagnosis should be made early and efficiently. Without it we cannot have meaningful discussions with the patient or plan treatment, and the patient's legal position in terms of compensation remains unclear. At the same time we try to control any pleural effusion to maintain breathing as long as possible.⁶ This is best done by thoracoscopic talc pleurodesis, which can usefully be combined with surgical biopsy. Then with the diagnosis made the disease can be staged. If the pathological stage is early extrapleural pneumonectomy should be considered, and we would recommend that this is done in the context of multimodality treatment and within a study.¹¹ If the tumour is inoperable management can be with chemotherapy, and again it would be preferable that this is within a study.¹²

This disease is increasing in frequency. There is nothing we can do now to prevent it in workers exposed to asbestos throughout the 1950s, 1960s, and 1970s. What we can do is recognise it early, treat it actively, and learn about best treatment with carefully thought out studies because we will be seeing many more mesotheliomas in the next 25 years. In the developed world alone 100 000 people alive now will die from it.

Tom Treasure, professor
Cardiothoracic Unit, Guy's Hospital, London SE1 9RT

David Waller, consultant thoracic surgeon
Glenfield Hospital, Leicester LE3 9QP

Simon Swift, research registrar
Thoracic Surgery, Guy's Hospital, London SE1 9RT

Julian Peto, professor of epidemiology
Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG

References

1. White C. Annual deaths from mesothelioma in Britain to reach 2000 by 2010. BMJ 2003;326: 1417

2. Johnson R, McIvor A. Lethal work: a history of the asbestos tragedy in Scotland. East Linton: Tuckwell, 2000.

3. Peto J, Hodgson JT, Matthews FE, Jones JR. Continuing increase in mesothelioma mortality in Britain. Lancet 1995;345: 535-9.

4. Peto J, Decarli A, La Vecchia C, Levi F, Negri E. The European mesothelioma epidemic. Br J Cancer 1999;79: 666-72.

5. Price B. Analysis of current trends in United States mesothelioma incidence. Am J Epidemiol 1997;145: 211-8.

6. British Thoracic Society. BTS statement on malignant mesothelioma in the United Kingdom, 2001. Thorax 2001;56: 250-65.

7. Tan C, Swift S, Gilham C, Shaefi S, Fountain SW, Peto J, et al. Survival in surgically diagnosed patients with malignant mesothelioma in current practice. Thorax 2002;57iii: iii36.

8. Edwards JG, Abrams KR, Leverment JN, Spyt TJ, Waller DA, O'Byrne KJ. Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems. Thorax 2000;55: 731-5.

9. Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 1976;31: 15-24.

10. Butchart EG. Contemporary management of malignant pleural mesothelioma. Oncologist 1999;4: 488-500

11. Treasure T, Swift S, Tan C. Radical surgery for mesothelioma: how can we obtain evidence? World J Surg 2003;27: 891-4.

12. Girling DJ, Muers MF, Qian W, Lobban D. Multicenter randomized controlled trial of the management of unresectable malignant mesothelioma proposed by the British Thoracic Society and the British Medical Research Council. Semin Oncol 2002;29: 97-101

*** POSTED FEBRUARY 2, 2004 ***