Invited Commentary (DOI: 10.1007/s00268-004-1046-6)

Published Online: August 3, 2004

Carol Tan, M.B.Ch.B.,1 Artyom Sedrakyan, M.D., Ph.D.,2

Tom Treasure, M.D., M.S.1

1Thoracic Unit, Guy’s Hospital, London, UK2Health Services Research Unit, London School of Hygiene and TropicalMedicine and Clinical Effectiveness Unit, Royal College of Surgeons ofEngland, London, UK

The paper by Haddad et al. is important and a good example ofclinical research: (1) it addresses a common and disabling clinicalproblem; (2) they have performed a scientifically correct random-ized controlled trial (RCT); and (3) the results can be directly ap-plied to guide best practice.

Malignant pleural effusion is a frequent manifestation of all thecommon cancers. If the pleura is drained to dryness and fusion ofthe visceral and parietal pleura is achieved, the patient can bespared recurring breathlessness and the need for repeated inter-ventions and hospital visits. Effective, efficiently achievedpleurodesis is an important contribution to the care of patients withcancer.

There have been many publications on the management of ma-lignant pleural effusion. The practices and techniques employedvary widely and have been reviewed elsewhere [1]. The CochraneCollaboration (based in Oxford, UK) provides an up-to-date re-view of the evidence [2]. Both reviews concluded that talc is thesclerosing agent of choice. A search of the literature (PubMed)showed talc to be by far the commonest agent studied, althoughbleomycin is still widely used. This is probably because in a vagueway it seems like a good idea to use a chemotherapeutic agent todeal with cancer-related fluid; this has no logical basis because inmany cases the pleura itself is free of cancer. Involvement of medi-astinal lymphatics causes the fluid.

There are six RCTs in the literature comparing talc and bleomy-cin [3–8], one of which compares surgical VATS (Video AssistedThoracoscopic Surgery) talc insufflation with bleomycin deliveredthrough a thoracostomy tube [7]. The other five are more directlycomparable to the methods used by Haddad and colleagues. Thestudy populations are all small, including only 25 to 38 patients,about one-third to one-half the number of patients in the Haddadet al. study; similarly, most failed to reach significance. This is a

common problem in surgical studies; it is difficult to recruit suffi-cient numbers to have statistical power. This is the point at whichmeta-analysis is of value. If we combine the data of Haddad et al.with those of the other six studies (Fig. 1), we can see that thepooled result is significant and that there is consistency in the re-sults. The study of Haddad’s group is the largest and, taken with theothers, shows that talc is superior to bleomycin, consistently so.Modern health care is effective but expensive. As well as adoptingtreatments that are effective, we must stop spending money ontreatments that do not work or are less effective cost for cost. It istime to stop using bleomycin.

Studies are always selective; can the results be generalized? Aswith most studies, Haddad et al. used technical success as the mea-sure of outcome. We should not forget that the clinically importantobjective is palliation of symptoms, which is most reliably achievedwhen there is functioning underlying lung that is free to expand in apatient with a prognosis sufficiently long for the patient to benefit.When symptoms are severe, patients might want to undergo an in-tervention even if it has a low probability of complete technical suc-cess. This is reasonable, but such a decision should be an informedone. In our view, a modest but sustained symptomatic benefit isworth achieving for a patient with a long likelihood of survival; fora patient with only a few weeks to live, the benefit would have to begreater to justify the time in hospital for the procedure.

Fig. 1. Talc slurry compared to bleomycin for recurrence of malignantpleural effusion. The risk ratio (RR) or relative risk is the ratio of the failurerates. Where the ratios of the failure rates are less than 1.00, talc has thebetter results. This applies in six of seven studies (including that of Haddadet al.), although most are not individually significant.

References

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2. Shaw P, Agarwal R, Pleurodesis for Malignant Pleural Effusions(Cochrane Review). Cochrane Library, Issue 2 Chichester, Wiley, 2004;

3. Hamed H, Fentiman IS, Chaudary MA, et al. Comparison of intracavi-tary bleomycin and talc for control of pleural effusions secondary tocarcinoma of the breast. Br. J. Surg. 1989;76:1266–1267

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study comparing the efficacy of talc slurry and bleomycin in the treat-ment of malignant pleural effusions. Acta Clin. Belg. 1997;52:258–262

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7. Diacon AH, Wyser C, Bolliger CT, et al. Prospective randomized com-parison of thoracoscopic talc poudrage under local anesthesia versusbleomycin instillation for pleurodesis in malignant pleural effusions.Am. J. Respir. Crit. Care Med. 2000;162:1445–1449

8. Ong KC, Indumathi V, Raghuram J, et al. A comparative study ofpleurodesis using talc slurry and bleomycin in the management of ma-lignant pleural effusions. Respirology 2000;5:99–103

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