Differential Survival characteristics of sarcomatoid subtype biphasic pleural mesothelioma

Background: Biphasic mesothelioma (BPM) accounts for approximately 10% of all pleural mesothelioma. Our aim was to assess the clinical, radiological and pathological factors impacting survival in BPM and to better identify patients most likely to benefit from active treatment. Methods: Ten-year retrospective review of 214 biopsy-proven BPM cases with minimum 2-year follow-up. Patients with insufficient tissue for analysis were excluded (n=96). Clinical and pathological factors were evaluated along with radiological assessment of pleural thickness. Survival was measured from time of diagnosis. Uni- and multi-variable predictors of survival were evaluated. Results: 118 patients were included. 28 underwent pleurectomy/decortication (P/D), with 27 receiving additional modalities. 90 underwent chemotherapy (n=18) or radiotherapy alone (n=9), 63 received combination therapy, and 27 received best supportive care (BSC). Median overall survival was 11.2 months (0.3–36.2). At univariable analysis, P/D (p=0.0061), radiotherapy (RT; p<0.0001) and chemotherapy (p<0.0001) were associated with superior survival when compared to BSC alone. Pleurectomy-Decortication demonstrated 40% survival improvement compared with no surgery (p=0.122). In a multivariable model, the presence of necrosis was negatively prognostic (HR 2.1, SE 0.76). Furthermore, increased sarcomatoid component was associated with worse survival without radiotherapy. Conclusions: BPM prognosis remains poor despite multimodality treatment. Anti-cancer treatment is associated with superior outcome in this non-randomised retrospective series. Our findings suggest superior survival for those with a lower proportion of sarcomatoid disease, with selective benefit of RT in higher proportions of sarcomatoid disease. When planning active treatment, the potential survival benefits require balancing against associated morbidity and recovery period. The aim of this study was to determine significant prognostic factors in a specific cohort of patients with biphasic mesothelioma (BPM), in particular whether the proportion of sarcomatoid to epitheioid histology significantly affects survival outcomes. Furthermore, we aimed to determine whether there was any patient subgroup in which significant survival benefit may be gained from an aggressive multimodality approach. Some data addressing this question has previously been reported in previous studies. For patients undergoing surgery, superior survival has been reported for those with increased epithelioid component(12). Similarly, Alchami et al. showed a better overall survival in patients with epithelioid dominance, although this finding was not statistically significant(19). Our results demonstrate that chemotherapy, radiotherapy and pleurectomy/decortication are all associated with longer survival in biphasic mesothelioma, which may argue for using more aggressive trimodality therapy even in these patients. We also explored whether the extent of sarcomatoid component might be important. Although we demonstrate inferior survival in patients with ≥ 50% compared to <50% sarcomatoid component (4% vs. 12% at 2 years) this did not reach statistical significance. However, at a multivariable level ≥ 50% sarcomatoid component was associated with a 1.42 times greater death rate in patients not receiving radiotherapy. Furthermore, those patients with ≥ 50% sarcomatoid component who did receive radiotherapy had an 81% improved survival when compared to those with <50%. As such, these results suggest that patients with higher proportions of sarcomatoid disease have worse survival outcomes without radiotherapy, but radiotherapy may be less effective at prolonging survival in epithelioid predominance. This study is one of largest series of patients with exclusive biphasic mesothelioma (BPM) and includes patients at all stages undergoing surgical and non-surgical treatment. However, our results should be considered in the context of a number of limitations. Firstly, this is a retrospective single centre study performed over a 10-year period during which treatment approaches have been modified in accordance with clinical and technological developments. Second, in the majority of patients, diagnosis was made by pleural biopsy only, and as such the assessment of percentage sarcomatoid/epithelioid components is subject to the pleural sampling performed. Third, although 118 patients were included in this study, the number of surgical and non-surgical treatment modalities utilised results in a relatively small number of patients included in individual subgroups analysed. As such, the study may be underpowered to detect significant predictors of survival, particularly at the multivariable level given the interaction between multi-modal treatments and also the impact of extended surgery. Finally, it is important to note that treatment allocation in this retrospective series was not randomised, so interpretation of the efficacy of these therapies cannot be made with any certainty given the likelihood of selection bias.