Extrapleural Pneumonectomy Group Research Articles

Surgery for pleural mesothelioma in multimodality setting: comparison between surgical techniques in a high-volume center.

Pleural mesothelioma (PM) is an aggressive disease linked to asbestos exposure, presenting significant treatment challenges. The recommended approach is multimodal treatment, even if the concept of resectable PM and the superiority of one surgical technique over the other [(extended) pleurectomy decortication [(E)PD] vs extra-pleural pneumonectomy (EPP)] are matter of debates. The aim of this study is to compare the two techniques in terms of short- and long-term outcomes at a high-volume center. Clinical data from PM patients who underwent radical surgery [(E)PD and EPP] between 1994 and 2022 were collected. A propensity score weighting approach was used for non-random intervention allocation. Survival distribution was estimated using Kaplan-Meier method and the association with outcomes was evaluated using a weighted Cox Proportional Hazard Models. Among 254 patients, 125 (49%) underwent EPP and 129 (51%) (E)PD. The 90-day mortality was higher in the EPP group (7.2% vs 0%; p = 0.01). No difference in 1-,3- and 5-year survival was found: 65.8%, 26%, 17% for EPP and 75.5%, 39.7% and 21.3% for (E)PD; p = 0.39). The multivariable weighted Cox model identified no increased risk of death (HR 1.25; p = 0.49) or recurrence (HR 1.05; p = 0.858) in the EPP group. Pre-operative total lung capacity (TLC) was significantly associated with a reduced risk of death (HR 0.96; p = 0.023) and recurrence (HR 0.97; p = 0.019) at follow-up while preoperative disease burden to a higher risk of recurrence (HR 1.01; p = 0.02). Our experience showed acceptable short- and long-term outcomes in both procedures, making EPP still an option only for carefully selected patients at high volume center. Surgery, although recently debated, should be performed exclusively in expert centers to minimize post-operative risks. The identification of new prognostic factors is crucial for better selecting patients who may benefit from surgery within the context of multimodal treatment.

Multifactorial Evaluation following Cytoreductive Surgery for Malignant Pleural Mesothelioma in Patients with High Symptom-Burden.

Mesothelioma has a scant prognosis and a great impact on symptoms and the quality of life. Pleurectomy/decortication and extrapleural pneumonectomy are the two cytoreductive surgical strategies, with different invasiveness, but achieving similar oncological results. Hereafter, the two surgical procedures effects on symptoms and the quality of life are compared in a high symptom-burden population. Between 2003 and 2017, 55 consecutive patients underwent pleurectomy/decortication (n = 26) or extrapleural pneumonectomy (n = 29), both followed by adjuvant chemo-radiotherapy. Cardio-pulmonary function, symptoms and the quality of life (Short-Form-36 and St.George's questionnaires) were evaluated pre- and 3-, 6-, 12- and 24-months postoperatively. Extrapleural pneumonectomy demonstrated lower pain at 12 months but a higher decrement of forced vital capacity at 24 months than pleurectomy/decortication. Both procedures revealed a 3-months improvement of many symptoms and the quality of life determinants. Improvement in physical, social and pain-related measured parameters lasted for a longer time-spawn in the extrapleural pneumonectomy group. No differences were found in chemotherapy compliance and survival between groups. Age-at-presentation (p = 0.02) and non-epitheliod histology (p = 0.10) were the only significant prognosticators. Surgery, despite poor survival results, improved symptoms and the quality of life in patients with mesothelioma with high symptom-burden at diagnosis. Therefore, extrapleural pneumonectomy demonstrated the most durable effects.

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

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.

Single-Center 20-Year Experience in Surgical Treatment of Malignant Pleural Mesothelioma.

Objectives: We examined a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent surgery in our institution during the last 20 years. Across this period, we changed our surgical approach to MPM, adopting extended pleurectomy and decortication (eP/D) instead of extrapleural pneumonectomy (EPP). In this study, we compare the perioperative outcomes and long-term survival of patients who underwent EPP vs. eP/D. Methods: A retrospective analysis was carried out of all the MPM patients identified from our departmental database who underwent EPP or P/D from 2000 to 2021. Clavien–Dindo criteria was adopted to score postoperative complications, while Kaplan–Meier methods and a Cox multivariable analysis were used to perform the survival analysis. Results: Of 163 patients, 78 (48%) underwent EPP and 85 (52%) eP/D. Induction chemotherapy was significantly administrated more often in the eP/D group (88% vs. 51%). Complete trimodality treatment including induction chemotherapy, radical surgery, and adjuvant radiotherapy was administered in 74% of the eP/D group versus 32% of the EPP group (p < 0.001). The postoperative morbidity rate was higher in the eP/D group (54%) compared to the EPP group (36%) (p = 0.02); no statistically significant differences were identified concerning major complications (EPP 43% vs. eP/D 24%, p = 0.08). No statistical differences were identified in 30-day mortality, 90-day mortality, median disease-free, and overall survival statistics between the two groups. The Cox multivariable analysis confirmed no induction chemotherapy (HR, 0.5; p = 0.002), RDW (HR, 1.08; p = 0.02), and the presence of pathological nodal disease (HR, 1.99; p = 0.001) as factors associated with worse survival in the entire series. Conclusions: Our data support that eP/D is a well-tolerated procedure allowing the implementation of a trimodality strategy (induction chemotherapy, surgery, and radiotherapy) in most MPM patients. When eP/D is offered in this setting, the oncological results are comparable to EPP. To obtain the best oncological results, the goal of surgical resection should be macroscopic complete resection (R0) in carefully selected patients (clinical N0).

Does mediastinal lymph node involvement influence the surgical outcome in malign pleural mesothelioma?

Background This study examined the effect of metastatic mediastinal lymph node involvement on the prognosis of patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP) or extended pleurectomy (E/P) and also to assess the effect of metastatic mediastinal lymph node involvement on the prognosis of patients with MPM in these group of patients. Methods This retrospective study included 84 patients with MPM (66 men [78.6%] and 18 women [21.4%]) who underwent EPP (n = 44) or E/P (n = 40) at our institution between January 2001 and July 2019. Survival analyses were performed according to histopathology, nodal status, and surgical approach. Results In the EPP group, patients with T2-N2 status had a significantly better mean survival (17 ± 2.1 months) than patients with T3-N2 (7.3 ± 1.6 months) or T4-N2 (3.2 ± 1.1 months) status (p = .001). In the E/P group, patients with T2-N2 status had a mean survival of 18 ± 1.1 months, while patients with T3-N2 and T4-N2 status had mean survival durations of 6.6 ± 1.6 and 4.8 ± 1.2 months, respectively (p = .159). In both treatment groups, the survival rates of patients with epithelial tumors were better than those of patients with non-epithelial tumors, independent of N status. None of the patients with N2 disease survived until 5 years postoperatively. Conclusion In summary, our results suggested that mediastinal lymph node metastasis negatively influenced the prognosis of patients with T3 MPM, regardless of treatment by EPP or E/P. Under these circumstances, preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration may be considered for patients with high-stage MPM who are scheduled for surgery with curative intent. In our study, N2 status was spotted as a significant factor affecting survival, nevertheless its significance in survival of pleural mesothelioma patients should be analyzed in multi-centered studies.

Quality of Life Is Not Deteriorated After Extrapleural Pneumonectomy vs. (Extended) Pleurectomy/Decortication in Patients With Malignant Pleural Mesothelioma.

Background: Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is highly abandoned due to high morbidity and mortality rates and impaired quality of life (QoL). However, there are still rare indications for this intervention. The aim of this longitudinal prospective study was to monitor QoL and lung function in patients undergoing EPP and compare the outcomes with extended pleurectomy/decortication [(E)PD].Methods: Between June 2013 and June 2017, 42 patients underwent induction chemotherapy followed by either EPP (n = 7) or (E)PD (n = 35). All patients filled out the EORTC QLC-C15-PAL, –LC13, and SF-36 self-rating questionnaires pre-operatively, 6 weeks and 4 months after the operation. Additionally, lung function was measured pre-operatively and 4 months post-operatively.Results: We observed no significant differences in all QoL categories (general global health, pain, and dyspnea) between both surgical procedures, over the whole observation period. Moreover, a general tendency toward restoration of the pre-operative QoL status was documented at 4 months after the both operations. Forced expiratory volume in 1 s (FEV1) showed a significant decrease after surgery in both the groups [EPP group p = 0.06 and (E)PD group p < 0.001]; also, the forced volume vital capacity (FVC) significantly decreased (EPP group p = 0.046 P/D group <0.001). Diffusion capacity did not show significant changes.Conclusion: According to these results, QoL is no longer severely impaired after EPP compared with EPD, and therefore should not be used as an argument against EPP in principle. However, indication has to be carefully evaluated for each patient.

Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy.

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263–0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521–0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137–0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897–0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.

Outcomes of Conversion to Extrapleural Pneumonectomy From Pleurectomy/Decortication for Malignant Pleural Mesothelioma

In recent years, there has been a shift from extrapleural pneumonectomy (EPP) toward pleurectomy/decortication (P/D) as the preferred surgical technique. However, we occasionally encounter difficult cases wherein visceral pleurectomy requires conversion to EPP from P/D. We sought to clarify the preoperative risk factors and clinical outcomes associated with conversion to EPP. We compared and analyzed conversion to EPP and P/D between September 2012 and December 2019. Conversion to EPP was decided in case of diffuse tumor invasion to the pulmonary parenchyma or due to failure of decortication. Univariable regression analysis was performed to determine the association of preoperative variables with conversion to EPP. Survival was analyzed by the Kaplan-Meier method and log-rank test. Of the 181 patients who underwent intended P/D, 145 (80.1%) patients underwent P/D and 18 (9.9%) patients underwent conversion to EPP. The sum of 3-level pleural thickness (P < 0.001), maximum of 3-level pleural thickness (P = 0.006), and clinical T stage (P < 0.001) demonstrated association with conversion to EPP. Overall survival and progression-free survival were significantly worse in the conversion to EPP group (median overall survival, 29.2 months vs 57.0 months [P = 0.008]; median progression-free survival, 15.3 months vs 23.2 months [P = 0.005]. Our data show that approximately 1 of every 10 patients with P/D intention converted to EPP. Preoperative pleural thickness and clinical T stage may be risk factors associated with conversion to EPP. The survival rate of conversion to EPP was worse than that of P/D.

Multimodality therapy for thymoma patients with pleural dissemination.

Although multidisciplinary treatment is recommended for patients with advanced stage and recurrent thymoma, a detailed treatment strategy remains controversial. We have performed a multimodality therapy of induction chemotherapy (CAMP therapy: cisplatin, doxorubicin, and methylprednisolone) combined with surgery for those patients. We now conducted a retrospective study for investigating the results of this multimodality therapy for thymoma patients with pleural dissemination. Between 2003 and 2017, 201 patients underwent surgical resection for thymomas. Twenty-six of them received induction CAMP therapy followed by surgery, and 19 of them with pleural dissemination were enrolled in this study. Those cohort were divided into 2 groups by employing surgical procedures: extrapleural pneumonectomy (EPP) group (n = 10) and resection of plural dissemination (RPD) group (n = 9). The median age of all patients was 49years. Based on the WHO classification, the histological diagnoses of those thymomas were as follows: Type B1 (n = 1), Type B2 (n = 13), and Type B3 (n = 5). Seven patients were complicated with myasthenia gravis (MG). Clinical stage of the 13 primary cases based on the Masaoka classification were stage IV, and the remaining six cases had recurrent pleural dissemination after surgery. Partial response in induction CAMP therapy was obtained in 78.9% (n = 15) of the patients. Adverse events (Grade 4) occurred in 2 patients (10.5%). Postoperative complications (Grade 4) were observed in 2 patients (10.5%). In all of the enrolled patients, the five-year overall survival rate (5Y-OS) and 5-year progression-free survival rate (5Y-PFS) were 76.7% and 55.1%, respectively. In the EPP group, 5Y-OS and 5Y-PFS were 83.3% and 83.3%, respectively, and in the RPD group, 70.0% and 29.6%, respectively. Multidisciplinary treatment using induction CAMP therapy and surgical resection for thymoma patients with pleural dissemination was effective and feasible. Because of the low recurrent rate of disease, young patients with good cardiopulmonary function and well-controlled MG might be good candidates for EPP.

Erratum: Outcomes of the Multimodal Treatment of Malignant Pleural Mesiothelioma: The Role of Surgery

[This corrects the article on p. 35 in vol. 51, PMID: 29430427.].

Outcomes of the Multimodal Treatment of Malignant Pleural Mesiothelioma: The Role of Surgery

BackgroundThe treatment of malignant pleural mesothelioma (MPM) is challenging, and multimodal treatment including surgery is recommended; however, the role of surgery is debated. The treatment outcomes of MPM in Korea have not been reported. We analyzed the outcomes of MPM in the context of multimodal treatment, including surgery.MethodsThe records of 29 patients with pathologically proven MPM from April 1998 to July 2015 were retrospectively reviewed. The treatment outcomes of the surgery and non-surgery groups were compared.ResultsThe overall median survival time was 10.6 months, and the overall 3-year survival rate was 25%. No postoperative 30-day or in-hospital mortality occurred in the surgery group. Postoperative complications included tachyarrhythmia (n=4), pulmonary thromboembolism (n=1), pneumonia (n=1), chylothorax (n=1), and wound complications (n=3). The treatment outcomes between the surgery and non-surgery groups were not significantly different (3-year survival rate: 31.3% vs. 16.7%, respectively; p=0.47). In a subgroup analysis, there was no significant difference in the treatment outcomes between the extrapleural pneumonectomy group and the non-surgery group (3-year survival rate: 45.5% vs. 16.7%, respectively; p=0.23).ConclusionMultimodal treatment incorporating surgery did not show better outcomes than non-surgical treatment. A nationwide multicenter data registry and prospective randomized controlled studies are necessary to optimize the treatment of MPM.

Radical multimodality therapy for malignant pleural mesothelioma.

Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness. To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma. We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017. We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status. Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE. We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated the evidence as moderate quality for overall survival and low quality for all other outcomes. One trial compared combined extrapleural pneumonectomy (EPP) plus neoadjuvant platinum-based chemotherapy plus postoperative high-dose hemithoracic radiotherapy with combined EPP plus platinum-based chemotherapy. The other trial compared EPP plus postoperative hemithoracic radiotherapy with standard (non-radical) therapy alone following platinum-based chemotherapy (patients in the standard therapy arm received continued oncological management according to local policy, which could include further chemotherapy or palliative radiotherapy).For the first trial, median overall survival calculated from registration was 20.8 months (95% confidence interval (CI) 14.4 to 27.8) in the no-radiotherapy group and 19.3 months (95% CI 11.5 to 21.8) in the radiotherapy group. For the second trial, median overall survival was 14.4 months (95% CI 5.3 to 18.7) for patients allocated to EPP and 19.5 months (95% CI 13.4 to time not yet reached) for patients randomised to standard non-radical therapy. In the second trial, 12 serious adverse events were reported during the study period: ten in the EPP group and two in the non-radical therapy group. Overall health-related quality of life scores were not different between the two arms in either study. We could not perform a meta-analysis of the two included trials due to clinical heterogeneity. We also identified three ongoing trials evaluating the topic of our review. The overall strength of the evidence gathered in this review is low and there is a lack of available evidence to support the use of radical multimodality therapy in routine clinical practice (particularly as one trial suggests greater harm). Given the added cost of multimodality treatment and the possible increase in risk of adverse effects, the lack of evidence of their effectiveness probably means that these interventions should currently be limited to clinical trials alone.

The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication

For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome. Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD. The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001). The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without detriment to overall survival.

Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy.

Surgical procedure for malignant pleural mesothelioma (MPM) remains controversial. We reviewed our protocol including pleurectomy/decortication (P/D) for patients with malignant pleural mesothelioma who were intolerable to extrapleural pneumonectomy (EPP). From June 2010 to April 2014, 14 patients with MPM were intended to treat with multimodality therapy including surgery. Four patients who were intolerable to EPP received a protocol consisting of P/D and intraoperative intrapleural hyperthermic cisplatin perfusion, followed by systemic chemotherapy. Ten patients received trimodality treatment of EPP, systemic chemotherapy, and intensity modulated radiation therapy for hemithorax. Surgical outcomes of acute operative results and interim survivals were examined and compared between the groups. All patients obtained macroscopic complete resection and received multimodality treatment in P/D and EPP groups. Operation time was longer in P/D group; however, there were no differences in ICU stays or hospitalizations. Four patients in P/D group and seven patients in EPP group experienced postoperative complications; however, there was no operative morality. EPP group suffered from cardiac complications and P/D group had prolonged airleak. Full walk recovery was obtained earlier in P/D group. One patient in P/D group had a local recurrence 11months after surgery, while the other three patients survived 23-41months with no evidence of diseases. P/D and intraoperative intrapleural cisplatin perfusion achieved a favorable macroscopic resection in patients with MPM who were intolerable to EPP. Postoperative complications were manageable and survival could be promising. Further study warrants with a larger number of patients.

Meta-Analysis of Survival After Pleurectomy Decortication Versus Extrapleural Pneumonectomy in Mesothelioma

This comprehensive meta-analysis was conducted to answer the question as to which procedure, pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) is more beneficial to malignant pleural mesothelioma patients' outcome. Original research studies that evaluated long-term outcomes of P/D versus EPP were identified, from January 1990 to January 2014. The combined percent perioperative and 2-year mortality, and median survival were calculated according to both a fixed and a random effect model. The Q statistics and I(2) statistic were used to test for heterogeneity between the studies. There were 24 distinct data sets, for a total of 1,512 patients treated with P/D, and 1,391 treated with EPP. There was a significantly higher proportion of short-term deaths in the EPP group versus the P/D group (percent mortality meta estimate; 4.5% vs 1.7%; p < 0.05). There was no statistically significant difference in 2-year mortality between the 2 groups, but there was significant heterogeneity. The reanalysis of the large number of studies comparing P/D to EPP suggests that P/D is associated with a 2 ½-fold lower short-term mortality (perioperatively and within 30 days) than EPP. Pleurectomy decortication should therefore be preferred when technically feasible.

Which type of surgery should become the preferred procedure for malignant pleural mesothelioma: extrapleural pneumonectomy or extended pleurectomy?

Since radiation and chemotherapy have limitations as therapies for malignant pleural mesothelioma (MPM). The type of surgery [extrapleural pneumonectomy (EPP), extended pleurectomy (E/P), and pleurectomy/decortication (P/D)] remains controversial. This study involves 76 consecutive patients. 58 of the cases were males (76%) with a median age of 53.17±10.93 years. EPP, E/P, and P/D were performed in 31, 20, and 25 cases, respectively. The median survival time was 20 months in all patients. Overall, five-year survival rate was 14.3%. The survival rate was significantly better in epithelioid mesothelioma (P=0.049). For EPP cases, the median survival rate was 17 months, and the three-to-five year survival rates were 21% and 17%, respectively. For E/P cases, the median survival rate was 27 months and the three-year and four-year survival rates were 34% and 30%, respectively. For P/D cases, the median survival rate was 15 months and the three-to-five year survival rate was 13% and 0%. There were no statistically significant differences between the three surgical techniques (P=0.088). A comparative analysis indicates only a statistically significant difference in the E/P and P/D comparison (P=0.032). Hospital mortality showed a higher trend in EPP group (EPP: 12.9%, E/P: 0% and P/D: 4%, P=0.145). N2 cases, there were no cases of two-year survival. The survival rate in N2 was comparatively much lower, which was statistically significant (P=0.005). In multivariate analysis, only P/D (OR 0.3, 95% CI: 0.1-0.9, P=0.049) and N2 (OR 1.6, 95% CI: 0.9-2.6, P=0.090) were found to be poor prognostic factors. E/P could be encouraged to EPP with lower mortality rate and better survival trend in MPM. N2 diseases were negative prognostic factors in MPM.

Pleurectomy/Decortication is Superior to Extrapleural Pneumonectomy in the Multimodality Management of Patients with Malignant Pleural Mesothelioma

To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant radiotherapy versus pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Nonrandomized prospective study of patients treated by multimodality therapy and operated on between January 2004 and June 2011. Second-line treatments were administered when appropriate. Survival and prognostic factors were analyzed by the Kaplan Meier method, log rank test, and Cox regression analysis. Twenty-five consecutive patients received neoadjuvant chemotherapy, 22 underwent EPP, and 17 received adjuvant radiotherapy. Over the same period, 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy. The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group. Fifteen patients (68%) in the EPP group and 15 (27.7%) in the P/D group experienced complications. There were no differences between the EPP and P/D groups for age, sex, histology, pathologic stage, and nodal status. Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group. Survival was significantly better in the P/D group: median survival was 23 months versus 12.8 months, 2-year survival was 49%versus 18.2 %, and 5-year survival was 30.1%versus 9%, respectively (p = 0.004). At multivariate analysis, epithelioid histology, P/D, and completeness of resection were independent prognostic factors. In our experience, P/D, hyperthermic pleural lavage with povidone-iodine, and adjuvant chemotherapy were superior to neoadjuvant chemotherapy, EPP, and adjuvant radiotherapy.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

SummaryBackgroundThe effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.MethodsMARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524.FindingsBetween Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92–3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21–6·26; p=0·016). Median survival was 14·4 months (5·3–18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group.InterpretationIn view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients.FundingCancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Outcome for Patients with Malignant Pleural Mesothelioma Referred for Trimodality Therapy in Western Australia

Trimodality therapy (TMT), consisting of extrapleural pneumonectomy (EPP), preoperative or postoperative combination chemotherapy, and high-dose hemithoracic radiotherapy, is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma (MPM). Thus, TMT was introduced as an option for such patients in Western Australia in 2004. However, TMT has never been compared with non-TMT therapy in the same patient population, thereby introducing a potential for selection bias. We performed a retrospective review of all patients referred for TMT consisting of EPP, adjuvant chemotherapy, and hemithoracic radiotherapy at a quaternary referral institution. Patient eligibility for referral for TMT was based on patients' tolerability for pneumonectomy, epithelioid subtype, and computed tomography and positron emission tomography scanning indicating operable disease, with the exclusion of extrapleural lymphadenopathy and metastatic disease (clinical stage T1-3N0-1M0). Eligible patients consenting to TMT also underwent a surgical staging procedure (bilateral thoracoscopy, mediastinoscopy, and laparoscopy) to confirm eligibility before EPP. Thirty-six patients have been referred for TMT since 2004, and there has been a median of 27 months follow-up; of 31 patients having surgical staging, eight were ineligible for EPP and one declined EPP. Of the 22 planned for EPP, 18 underwent EPP and four had unresectable disease at surgery. There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP (30-day mortality 11%); 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy. Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients (39%) and nonepithelioid subtype in six patients (33%). Local recurrence did not occur among EPP survivors; however, 56% (9 of 16 patients) developed distant recurrence. Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients (20.4 versus 20.7 months and 76 versus 78%, respectively; p = NS). In this case series, we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group. After surgical staging, 26% of patients were ineligible for TMT. Thus, surgical staging is essential before proceeding with EPP. Despite aggressive imaging and surgical staging, 39% of patients will have N2 disease and 18% will have unresectable disease at operation. Although complete locoregional control was achieved with TMT, distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy. We conclude that TMT for operable epithelioid MPM requires further assessment in randomized controlled trials.

Case-control study between extrapleural pneumonectomy and radical pleurectomy/decortication for pathological N2 malignant pleural mesothelioma☆

To compare the outcomes of extrapleural pneumonectomy (EPP) and radical pleurectomy/decortication (P/D) for N2 malignant pleural mesothelioma (MM). In a retrospective case-control study we analysed the results of the 57 patients [49 male and 8 female, median age 59 (range 14-70) years] who underwent radical surgery for MM found to have pathological N2 disease over a 7-year-period. EPP was performed on 45 and P/D on 12 patients. Prognostic factors, postoperative course, pathological data and postoperative survival were analysed. Those in the P/D group were significantly older (median age 62 vs 58 years, p=0.03) than in the EPP group. There was no difference in postoperative hospital stay (p=0.1) nor T stage (p=0.7) between the groups. There were no significant differences in the proportion of patients undergoing some adjuvant therapy in each group (p=0.2). Mean survival from diagnosis was 15 months in the EPP group and 16 months for those who underwent P/D (p=0.4). Preservation of the lung during radical surgery for N2 MM does not compromise survival even in an older group population. We therefore now have ceased to perform EPP in cases of N2 disease and we make every effort to accurately stage patients with mediastinoscopy to identify them.