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Ann Thorac Surg 2006;82:2337-2338
© 2006 The Society of Thoracic Surgeons
University of Texas M.D. Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery, 1515 Holcombe Blvd, Box 445, Houston, TX 77030-4009
(Email: drice{at}mdanderson.org).
Doctor Aelony [1] raises several important points in his letter regarding our article [2]. Probably the most salient is that despite advances in chemotherapy, radiotherapy, and surgery for mesothelioma, current therapeutic regimens are rarely curative. Nonetheless in highly selected patients treated with aggressive multimodality regimens, several authors have documented survival that exceeds that associated with the natural course of the disease in untreated patients [3, 4]. Prospective, randomized comparative data are currently lacking; however the Mesothelioma and Radical Surgery (MARS) trial, now in pilot phase in Europe, will attempt to answer the question of whether survival is improved by chemotherapy, surgery, and radiation therapy compared with chemotherapy and supportive care alone. Until the results of this important phase III trial are available (expected to be complete in the year 2012), we will continue to have to make treatment decisions based on imperfect and largely retrospective data.
Regarding involvement of extrapleural (N2) nodes, as Dr Aelony [1] rightly points out, these portend poor prognosis. Nevertheless there are occasional patients with N2 metastases who can achieve prolonged survival. In our series of 100 consecutive patients who underwent extrapleural pneumonectomy (EPP), but without chemotherapy, node negative patients with epithelioid tumors had median and 3-year survival rates of 26 months and 41%, respectively, compared with 11 months and 17% for node-positive patients. Of 40 patients with N2 disease, 6 (15%) survived more than 26 months, and 4 (10%) remain alive at 33, 37, 43, and 47 months, respectively. Two of these are without evidence of disease recurrence. We have not attempted to compare survival of this cohort of carefully staged patients with that of historical series of untreated, nonsurgical (and therefore inaccurately staged) patients, because potential stage imbalances would make such comparisons meaningless. Just as in lung cancer, nodal metastasis is most likely a marker for micrometastatic disease. Therefore it is not surprising that local therapy alone may be insufficient treatment for patients with stage III disease, and we now routinely incorporate systemic chemotherapy into the therapeutic regimens of patients with nodal metastases.
Although control of distant metastatic disease remains a challenge, significant progress in the local control of mesothelioma has been made by combining aggressive cytoreductive surgery with postoperative hemithoracic radiation [3]. In our initial experience, which included 32 patients who underwent EPP followed by intensity modulated radiation therapy, local control was achieved in 94%; however 50% of patients failed distantly [5]. Of the 32 patients, 91% were International Mesothelioma Interest Group stage III or higher.
Doctor Aelony [1] has reported good results with thoracoscopic talc pleurodesis (TTP) in a group of 26 patients treated during a 15-year period [6]. However, it must be noted that this symptom-relieving technique is appropriate only in patients who present with free-flowing effusions and in whom there is little encasement of the lung by tumor. Certainly in patients with low-volume disease, TTP will usually provide effective symptom control; however it is precisely this same group of patients that usually benefits the most from aggressive multimodality regimens. In addition, it is important to keep two facts in mind when comparing results of nonsurgical and surgical series. First, survival in a nonsurgical series is generally measured from the date of cancer diagnosis. Survival in nearly all surgical series is measured from the date of surgery, which generally occurs about 3 months after the date of diagnosis. Second, nonsurgical staging is notoriously inaccurate, so stage for stage comparisons between surgical and nonsurgical series are problematic.
With the recent emergence of more efficacious chemotherapy, improvements in hemithoracic radiation techniques, and continued refinements in staging and operative strategies, there is reason to hope that combined modality regimens for mesothelioma may soon begin to more positively impact the survival of patients with mesothelioma. Significant progress has been made in the local control of this once inexorably progressive disease. Our challenge for the future is to develop more effective adjunctive approaches to combat distant metastases. To this end, a variety of cytotoxic, immunotherapeutic, and biolocically targeted agents are currently under investigation. Therapy for this disease must continue to be forward looking and innovative. The nihilistic assumption that mesothelioma will forever be incurable, and should therefore be treated with only palliative intent, does little to advance the treatment of this disease. With the worldwide incidence of mesothelioma expected to continue well into the first half of this century, progressive and novel therapies are needed now more than ever.
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