Systematic Review and Meta-Analysis of Pleurectomy/Decortication versus Extrapleural Pneumonectomy in the Treatment of Malignant Pleural Mesothelioma

Abstract

Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant cancer for which there are poor treatment options. Extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) are the two most used surgical procedures in patients with resectable disease. We reviewed the available literature in order to compare the overall survival and postoperative complications of EPP and P/D and to provide evidence for the best procedure in the treatment of MPM. Methods: We performed a systematic review of the literature, including studies from August 2018 to May 2022. The primary outcome was 5-year overall survival (OS) and the secondary outcomes were 30-day mortality, 90-day mortality and peri-operative complications. Results: Thirteen studies were considered, including a total of 1624 patients treated with EPP and 2147 treated with P/D. The estimated pooled HR showed a significant lower hazard for P/D compared to EPP in terms of OS (HR = 0.76; 95% CI from 0.62 to 0.94; p < 0.001). In 12 studies, the risk for 30-day mortality was lower for patients treated with P/D (RR = 0.49; 95% CI from 0.31 to 0.76; p = <0.01), whereas only five studies reported 90-day mortality, and no statistically significant difference between EPP and P/D was found (RR = 0.71; 95% CI from 0.47 to 1.07; p = 0.10). The OS restricted mean survival time difference meta-analysis (RMSDT) confirms the superior survival of P/D on the EPP, a superiority that increases from 0.54 months at one year to 4.23 at five years. The incidence of postoperative empyema, atrial fibrillation, bleeding and bronchopleural fistula was significantly increased in the EPP group except for prolonged air leakage, which is only characteristic of P/D. Conclusions: Using two different statistical methods, this meta-analysis suggests that long-term survival after surgical treatment for resectable MPM is greater for patients undergoing P/D. Long-term survival had never been previously analyzed with appropriate tests; on the contrary, our result is consistent with the previous meta-analyses and reinforces the evidence of lower 30-day mortality and the prevalence of postoperative complications in P/D versus EPP patients. The recent introduction of innovative therapeutic schemes, both adjuvant and neoadjuvant therapy, keeps the discussion on surgical strategy open and will require new studies.

Keywords: EPP; malignant pleural mesothelioma; mesothelioma; mpm; pleurectomy; pleurectomy/decortication (P/D); pneumonectomy.

Figure 1

PRISMA flow diagram for study review and inclusion.

Figure 2

Forest plot of the hazard ratio (HR) for overall survival of all-cause mortality after pleurectomy/decortication (P/D) versus extrapleural pneumonectomy (EPP) in the treatment of malignant pleural mesothelioma [16,17,18,19,20,21,22,23,24,25,26,27,28]. The pooled HR with 95% confidence interval (CI) using a random effects model is 0.76, in favor of P/D. The test of heterogeneity between the studies within a subgroup is shown below in the summary statistics.

Figure 3

Funnel plot for overall survival. The dots asymmetric distribution indicates possible publication bias.

Figure 4

Restricted mean survival time difference (RMSTD) for all selected studies. Each color represents a single study. For every color there are dashed (PD) and continued (EPP) tracts. The pooled RMSTD with relative 95% confidence interval using different statistical estimations is represented by black points (triangle, circle, square and rhombus).

Figure 5

Forest plot of the relative risk (RR) for 30-day mortality after pleurectomy/decortication (P/D) versus extrapleural pneumonectomy (EPP) [16,17,18,20,21,22,23,24,25,26,27,28]. The pooled RR with 95% confidence interval (CI) using a random effects model is 0.49, in favor of P/D. The I² index shows low heterogeneity.

Figure 6

Funnel plot for 30-day mortality. The dots symmetric distribution indicates low publication bias.

Figure 7

Forest plot of the relative risk (RR) for 90-day mortality after pleurectomy/decortication (P/D) versus extrapleural pneumonectomy (EPP) [16,19,20,26,28]. The pooled RR using a random effects model does not differ between the two treatments. The test of heterogeneity between the five studies within a subgroup is shown below in the summary statistics.

Figure 8

Forest plot of the relative risk (RR) for total postoperative complications after pleurectomy/decortication (P/D) versus extrapleural pneumonectomy (EPP) [16,17,18,20,21,22,23,24,25,26]. The pooled RR using a random effects model shows a significative lower risk of complication for P/D. The test of heterogeneity between the 10 studies within a subgroup returns a high value.

Figure 9

Forest plots of the relative risk (RR) for major perioperative complications. (A) Empyema [16,17,18,20,21,22,24,25,26,28]. (B) Atrial fibrillation. (C) Hemorrhage. (D) Prolonged air leakage. (E) Myocardial infarction. (F) Pulmonary embolism.