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Eur J Cardiothorac Surg 2007;31:770-771. doi:10.1016/j.ejcts.2007.03.004
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Editorial comment

Chief, Division of Thoracic Surgery, Brigham & Women's Hospital, Professor of Surgery, Harvard Medical School Boston, MA 02115-6195, USA

^_* Corresponding author. Tel.: +1 617 7325004; fax: +1 617 5666434. (Email: dsugarbaker{at}partners.org).

At this time, the rationale for aggressive surgical resection in malignant pleural mesothelioma (MPM) is established. The role of extrapleural pneumonectomy in resecting patients with tumors confined to the hemithorax appears to be established, at least as an initial consideration in patients presenting with MPM. A controversy arises over which is the best to perform operation—extrapleural pneumonectomy (EPP) or pleurectomy and decortication (P/D). Suffice it to say the expectation for both procedures is limited to the removal of gross disease. The goal of achieving a macroscopic complete resection, in my view, has become the central focus of surgeons in assessing the role of surgery in mesothelioma [1]. The impact of node status is no longer open to question. In 1993, we identified lymph node involvement as a clear prognostic marker in MPM [2]. Furthering this analysis, we subsequently reported involvement of N2 or extrapleural nodes to be an independent negative prognostic factor [3].

It is important, however, when assessing the role of surgery, as the group in Leicester has done, to be cognizant of other significant prognostic factors that impact survival. The principal factor affecting survival in mesothelioma is cell type. Indeed, in the palliative setting, alone, patients with epithelial tumors do much better than those with the sarcomatoid or mixed histologic subtypes [4]. Many publications report better outcome with the epithelial subtype in the setting of multimodality treatment [5,6]. Moreover, the combination of N2 disease and mixed or sarcomatoid cell type demonstrates extremely poor prognosis [3]. It is therefore important to examine the number of patients with pure epithelial versus biphasic tumors in the present group. The absolute bulk of disease is another important prognostic factor in MPM [7]. Many patients are candidates for EPP only because of the sheer bulk of their disease.

The authors state that survival is equivalent between the P/D and EPP groups, but the follow-up data are not mature or balanced enough to support this conclusion. The survival estimate for P/D is based on four events among 12 patients, with many observations censored after limited follow-up. In Figure 3, only 2 P/D patients surviving beyond 12 months can be discerned. In addition, Table 2 indicates an imbalance in the proportion of patients with biphasic tumors between the two segments of this cohort. Specifically, 29% of patients in the EPP group (13 of 45) had mixed histology, compared to only 17% of patients in the P/D group (2 of 12). This imbalance, favoring a higher percentage of biphasic disease in the EPP N2 group, while not statistically significant in this small cohort, would make meaningful survival comparison difficult. Likewise the Kaplan–Meier survival curve in Figure 3 makes no distinction between histologic subtypes.

It appears that this retrospective analysis by Martin-Uncar et al. [8] has raised a significant question as to whether N2 disease should be the subject of MPM protocol therapy in mesothelioma. The choice of surgical procedure, and indeed, the role of surgical resection remain poorly defined in patients with extrapleural or N2 nodes pending prospective study. Whether patients should undergo induction chemotherapy in this setting to be followed by complete surgical resection and hemithoracic radiation remains the subject of future trials.

Going forward, I would propose a new standard for reporting outcome that recognizes epithelial cell malignant pleural mesothelioma as a cancer separate and distinct from the biphasic/sarcomatoid variety, in much the same way that we currently report outcome for non-small cell lung cancer independent of small cell lung cancer. Precise information that correlates distinct clinical subtypes with survival and other prognostic factors will be important for future comparative analysis, particularly as we become more knowledgeable about the molecular basis for each of these entities and more adept at developing new biomarkers and tailoring individualized treatments.

	References

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1. Sugarbaker DJ. Macroscopic complete resection: the goal of primary surgery in multimodality therapy for pleural mesothelioma. J Thorac Oncol 2006;1(2).
2. Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, Corson JM, Antman KH. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelima. J Clin Oncol 1993;11:1172-1178.[Abstract/Free Full Text]
3. Sugarbaker DJ, Flores RM, Jaklisch MT, Richards WG, Strauss GM, Corson JM, decamp MM, Swanson SJ, Bueno R, Lukanich JM, Healey-Baldini E, Mentzer SI. Resection margins, extrapleural nodal status and cell type determine survival in trimodality therapy of malignant pleural mesothelioma. Results I 183 patients. J Thorac Cardiovasc Surg 1999;117:54-65.[Abstract/Free Full Text]
4. Van Gelder T, Damhuis RA, Hoogsteden HC. Prognostic factors and survival in malignant pleural mesothelioma. Eur Respir J 1994;7:1035-1038.[Abstract]
5. Takahashi K, Yoshida J, Nishimura M, Nagai K. Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma. A treatment option in selected cases?. Jpn J Thorac Cardiovasc Surg 2001;49:89-93.[CrossRef][Medline]
6. Ceresoli GL, Locati LD, Ferreri AJ, Cozzarini C, Passoni P, Melloni G, Zannini P, Bolognesi A, Villa E. Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma. Lung Cancer 2001;34:279-287.[CrossRef][Medline]
7. Pass HI, Temeck BK, Kranda K, Steinberg SM, Feuerstein IR. Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma. J Thorac Cardiovasc Surg 1998;115:310-317.[Abstract/Free Full Text]
8. Martin-Ucar, Nakas A, Edwards JG, Waller DA. Case-control study between extrapleural pneumonectomy and radical pleurectomy/decortication for pathological N2 malignant pleural mesothelioma. Eur J Cardiothorac Surg 2007;31:765-770.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David J. Sugarbaker Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sugarbaker, D. J. Search for Related Content PubMed Articles by Sugarbaker, D. J.