Mesothelioma Information - Mesothelioma Asbestos
Surgical Treatment
Surgery in mesothelioma can be radical, debulking or palliative. Radical surgery (pleuropneumonectomy) aims to eradicate all macroscopic disease and is therefore feasible only in stage I or early stage II disease (involved nodes or early localized chest wall invasion). All of the ipsilateral pleura, lung and pericardium are removed and, because diaphragmatic pleura cannot be separated from the diaphragmatic muscle for embryological reasons, it is necessary to remove the hemidiaphragm also as part of the procedure. Visualization of the diaphragm is facilitated by two levels of access to the chest through the same skin incision (Fig. 1) [7], although some surgeons use a single thoracotomy incision [17].
Debulking surgery involves parietal pleurectomy (leaving diaphragmatic pleura in place) and decortication of the lung (inevitably leaving some tumor on or in the lung in most cases) and is usually combined with other treatment modalities. Pleuropneumonectomy is a very major operation and in the author's view has no place as a debulking procedure, for example leaving the diaphragm in place with tumor covering it in the so-called "modified" pleuropneumonectomy procedure. Palliative surgery ranges from thoracoscopy and talc pleurodesis to more limited pleurectomy to achieve pleural symphysis [7].
The diagram on the left shows the division of the diaphragm outside the pleural reflection, preserving the peritoneum. The middle diagram represents the division of the pericardium outside the pleural reflection. The diagram on the right shows the completion of the pneumonectomy intrapericardially and en bloc excision of mediastinal lymph nodes. ICS = intercostal space. The firm attachment of the parietal pleura to the diaphragm and pericardium is shown by the hatched lines.
Margin of clearance is an issue which continues to cause controversy. If pleuropneumonectomy has been used as a debulking procedure only, margins will clearly be positive. Even if it is used radically with "curative intent" in early disease, performing an "extracapsular" excision by staying outside the parietal pleura and resecting the diaphragm (Fig. 1), margins of clearance will be very small. The definition of "negative resection margins" depends on the criteria used by each pathologist and on the number and location of sites sampled on each specimen.
Radical surgery is a major operation, suitable only for fit patients with normal cardiopulmonary function. In the past, pleuropneumonectomy has been condemned on the grounds of high mortality and morbidity and failure to achieve more than short to medium-term palliation. However, the results of pleuropneumonectomy in the literature need to be interpreted with caution. Many of the early reports in the literature were anecdotal accounts of two or three cases.
Some authors summated the anecdotal reports of others and attempted to draw conclusions about the efficacy of the operation. In addition, interpretation of almost all series is hindered by one or more of the following factors:
- Lack of information on preoperative performance status.
- Lack of staging information, making it likely that some unsuitable tumors of advanced stage were submitted to surgery.
- Selection bias, with only more advanced disease being submitted to pleuropneumonectomy, early disease being treated with pleurectomy/decortication.
- Lack of precise histological typing and even confusion with secondary adenocarcinoma.
- Lack of detail about preoperative interventions such as tube drainage of effusion, thoracoscopy or open pleural biopsy, which could have seeded tumor into the chest wall.
- Varied surgical technique, with some techniques certain to leave residual tumor, e.g. failure to resect the affected hemidiaphragm.
- Lack of information about adjuvant therapy or varied adjuvant therapy.
In recent years surgical mortality has fallen to a level similar to that of pneumonectomy for lung cancer in centers with a large experience of pleuropneumonectomy, and it has become apparent that pleuropneumonectomy combined with chemotherapy and radiotherapy extends survival in some categories of patients, particularly those with pure epithelial histological type and no lymph node involvement [17].
Sugarbaker and colleagues in Boston have done much to revive interest in radical surgery for mesothelioma in recent years [17]. For many years it has been apparent that pleuropneumonectomy alone could not eradicate the tumor, even in stage I, because of small margins of clearance and the risk of tumor seeding, and that it would be necessary to combine the operation with other treatment modalities [6]. The Boston group has used both chemotherapy and radiotherapy after pleuropneumonectomy.
Unfortunately, because their protocol has changed at various times over the years and they have not disaggregated the data, it is impossible to determine which combination, if any, has been most successful. Prior to 1985, a combination of doxorubicin and cyclophosphamide was used; between 1985 and 1994 cisplatin was added to this regime; between 1995 and 1997 the regime was changed to carboplatin and paclitaxel.
Throughout the period of analysis external radiation therapy was used in all patients to treat the hemithorax, mediastinum and areas of residual tumor or localized positive resection margins, but the radiation dose to the mediastinum in particular appears to have been higher in recent years [17]. A further change in protocol has now been made with the use of hyperthermic intrapleural cisplatin postoperatively [25].
In recent years the results achieved by Sugarbaker and colleagues have been better than those previously reported for any treatment combination in mesothelioma (particularly in certain subsets of patients) [17]. Despite their rather surprising previous finding that positive resection margins or residual local disease did not influence survival [26], in their most recently published results on a larger series of patients, they draw attention to positive resection margins, lymph node (N2) involvement and nonepithelial histology as adverse predictors of survival [17]. Patients with epithelial histology, negative resection margins and negative lymph nodes achieved 68% two-year and 46% five-year survival [17]. These results are extremely encouraging and, if confirmed by other investigators in well-designed trials, offer considerable promise for younger, fitter patients presenting with stage I epithelial histology. They also provide scope to combine trimodality therapy with other innovative forms of treatment in the hope of improving results still further. Intrapleural interleukin 2 (IL-2) for example is reported to have a 55% response rate in early disease [27].
Pretreatment with IL-2 would thus be an approach worth evaluating. Gene therapy, which is also discussed below, may similarly have a role either pre- or postoperatively.
Based on currently available evidence, fit patients with stage I epithelial mesothelioma should be offered pleuropneumonectomy followed by chemotherapy and radiotherapy. But at present, it would appear that patients with sarcomatous histology or involved intrathoracic nodes will derive little benefit from trimodality therapy according to the protocols used by Sugarbaker and colleagues [17]. However until further trials have explored other chemotherapy regimes more targeted to sarcomatous tumors rather than epithelial tumors, it is probably too early to rule out this approach altogether in these patients.
Debulking surgery (pleurectomy and decortication) in combination with radiation therapy, using intraoperative brachytherapy and postoperative external beam radiation, has been reported to extend survival [28]. The place of pleurectomy/decortication has been reviewed by Rusch [16, 29] contrasting the results to pleuropneumonectomy in a personal series [16]. Median survival was greater in the pleurectomy/decortication group, but patients undergoing pleuropneumonectomy had more advanced disease and in many cases did not receive any adjuvant therapy, unlike the pleurectomy/decortication group, rendering the comparison invalid. The pattern of recurrent disease differed between the two groups of patients, with local recurrence tending to occur after pleurectomy/decortication and distant metastases after pleuropneumonectomy [16]. The risk of local recurrence after debulking surgery was not diminished by adjuvant therapy [29]. Nevertheless it was concluded that this combination of therapy remained a useful form of treatment for patients whose medical condition precluded pleuropneumonectomy [29].
Although unlikely to eradicate the disease, debulking surgery has a place in abolishing pleural effusion, controlling symptoms such as chest wall pain and extending survival when combined with other treatment modalities. It can also be used as a surgical alternative in the patient who is found at operation for planned pleuropneumonectomy to be unsuitable for this procedure because of unexpected local invasion. Thus, in otherwise fit patients, a thoracotomy is rarely a "wasted" or "unnecessary" operation in early mesothelioma, at least in cases of epithelial type. Although the data in favor of pleuropneumonectomy are persuasive, at least for epithelial mesothelioma, the choice between pleuropneumonectomy and pleurectomy/decortication in stage I disease in patients fit enough for either procedure will only be put on a scientific basis by randomized trials of one surgical procedure or the other in combination with the same adjuvant therapy. Such trials have never been performed.
Limited palliative surgery in the form of thoracoscopy and talc pleurodesis to eradicate effusion is useful in patients who cannot tolerate more extensive surgery. However, adhesion between visceral and parietal pleura can only be achieved if the underlying lung will expand sufficiently to meet the chest wall. Often a rind of tumor on the lung surface will prevent this from occurring. If this is the case, a limited thoracotomy and decortication of the affected area of lung may be successful [7]. An alternative approach would be the use of intrapleural chemotherapy or immunotherapy in an attempt to reduce the bulk of tumor on the lung surface.
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