Perioperative discordance in mesothelioma cell type after pleurectomy/decortication-a possible detrimental effect of neoadjuvant chemotherapy due to epithelial to mesenchymal transition?

Abstract

To evaluate the accuracy of preoperative histological assessment, factors affecting the accuracy and the subsequent effect on postoperative survival after surgical treatment for malignant pleural mesothelioma(MPM). We analysed the perioperative course of patients who underwent surgery for MPM in a single institution over a 5-year period. The primary endopoint was to evaluate the proportion of histological discordance between preoperative assessment and postoperative histology, while the secondary end-point was to evaluate its prognostic effect on postoperative survival after surgical treatment. One-hundred and twenty-nine patients were included in this study. Histological discordance between preoperative assessment and postoperative histology was found in 27 of 129 patients(20.9%):epithelial to biphasic/sarcomatoid(negative discordance) in 24, and biphasic to epithelial(positive discordance) in 3(p-value < 0,001).All 24 patients exhibiting epithelial-to-mesenchymal transition(EMT) had received neoadjuvant chemotherapy(p-value : 0,006).In the 34 patients who underwent upfront surgery, only one case(2.9%) of EMT was identified(p-value : 0,127).EMT was not associated with a less invasive method of biopsy(p-value : 0.058) nor with the volume or maximum diameter of the biopsy(p-value : 0,358 and 0,518, respectively) but it was significantly associated with the receipt of neoadjuvant chemotherapy(p-value : 0,006).At median follow-up of 17 months(IQR : 11.0-28.0),50(39%) patients are still alive. Overall survival was significantly reduced in those patients who received neoadjuvant chemotherapy and exhibited discordance(EMT) compared to those who did not : 11(95% CI : 6.2-15.8)months vs 19(95% CI : 14.2 -23.8) months(p-value < 0,001). In addition, there was no difference in overall survival between those who received neoadjuvant chemotherapy and those who had upfront surgery : 16(95% CI : 2.5-19.5)months vs 30(95% CI : 11.6-48.4)months(p-value : 0,203). The association of neoadjuvant chemotherapy with perioperative histological discordance can be explained by EMT, which lead to worse survival. Therefore, there is an argument for the preferential use of upfront surgery in the treatment of otherwise resectable MPM.