Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma

Abstract

One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM) seen between 1986 and 1999 at the authors’ Institution were reviewed. Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%) and mixed in 12 (10%). Ninety-one patients received a treatment (38 palliative pleurectomy and no further therapy, 16 palliative pleurectomy followed by chemotherapy, 37 chemotherapy alone), while 30 were referred to supportive care only. Median survival of the whole population was 10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%, respectively. Univariate analysis of subgroups showed that poor performance status (PS), non-epithelial histotype, Butchart stage>I and International Mesothelioma Interest Group (IMIG) stage>I were individually associated with lower survival. Patients receiving any therapy survived longer than patients treated with supportive care only (P=0.0004). Treatment modality had an independent prognostic value (P=0.00005), with a survival advantage for patients receiving surgery and adjuvant chemotherapy. Multivariate analysis confirmed the independent prognostic value of PS (P=0.001; HR=2.48) and treatment modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and treatment modality (P=0.01) was confirmed in the subset of patients with epithelial histology. On the contrary, therapy had no impact on survival in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of a retrospective non-randomized evaluation of treatment-related factors, patients with good PS and epithelial histology seemed to have a survival benefit from surgery or multimodality therapy, as opposite to patients with poor PS or non-epithelial histotype. However, these results must be confirmed in a larger prospective trial with uniform treatment.

Introduction

In spite of several therapeutic efforts and some encouraging results in selected series [1], the prognosis of malignant pleural mesothelioma (MPM) remains dismal [2], [3], [4], [5], and no clear consensus on the therapeutic approach exists. Furthermore, no randomized studies showing a clear survival benefit for aggressive treatment in comparison with supportive care alone have been performed [5]. Therapeutic improvements are limited by the lack of a definitive staging system and well defined prognostic factors. Several staging systems have been used, making different studies difficult to compare. The system proposed by Butchart et al. [6] was the most commonly used in older studies; more recently, a new classification has been proposed by the International Mesothelioma Interest Group (IMIG) [7]. A number of studies on large series have addressed the issue of prognostic indicators [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. Performance status, stage of disease and histology were found the most important ones, although significance for these variables was not always observed.

There is evidence that the incidence of MPM is rapidly increasing in the Western Countries [27], [28], with an expected peak around the year 2020. Further efforts are therefore needed to assess new experimental therapies. On the other hand, outside of clinical trials it is important to distinguish patients most likely to benefit from current surgical or multimodal approaches from those patients with a very poor prognosis who are better candidates for supportive care alone.

The present paper reports treatment outcome and prognostic factors of a retrospective series of 121 patients with MPM, mainly focusing on the relevance of histologic categorization in therapeutic decisions.