New Era for Malignant Pleural Mesothelioma

Updates on Therapeutic Options

Anne S. Tsao, MD, MBA; Harvey I. Pass, MD; Andreas Rimner, MD; Aaron S. Mansfield, MD


J Clin Oncol. 2022;40(6):681-692. 

In This Article


The surgical management of pleural mesothelioma demands compulsive preoperative staging with imaging and ideally with mediastinoscopy or endobronchial ultrasound, as well as proper selection of patients with a performance status and cardiopulmonary reserve who could tolerate possible extrapleural pneumonectomy (EPP).[35] The goal of the surgery remains macroscopic complete resection, which, in reality, is an R1 resection in the majority of cases.[36] Whether patients should have attempted macroscopic complete resection with or without induction therapies including chemotherapy or radiation, or whether postoperative adjuvant therapy without induction is preferable remain unanswered questions.[37,38] The extent of the resection for pleural mesothelioma has also evolved from being based chiefly on retrospective case series from large volume centers over the past 30 years.[39,40]

EPP, except in a specific protocol, ie, Surgery for Mesothelioma after Radiation Therapy, has largely been replaced by the use of either pleurectomy decortication or extended pleurectomy decortication, but remains as an option for good-risk patients for whom a satisfactory lung-sparing procedure cannot be performed. Although the mortality for EPP has decreased to as low as 1%-4% in high-volume centers, the pleurectomy options are associated with consistently lower mortality and morbidity. This is especially demonstrated in centers in which the same mesothelioma surgeon performed both procedures.[41–43] Recent data suggest that tumor T status may discriminate which patients are the best candidates for lung-sparing procedures.[44] T1 and T2 tumors have been associated with median survivals approaching 69.8 months in patients with epithelial tumors, whereas results of pleurectomy/decortication for T3 and T4 tumors have not had the same long-term survival outcomes except in selected series.

Despite these long-term survivals, there is still significant attrition of presumed surgical candidates, with the best series demonstrating that only 60%-80% of patients planned for surgery will go on to complete a resection. Moreover, a significant portion of these patients are found to have unresectable disease. Upstaging at the time of surgical resection is unfortunately a common occurrence in up to 70%-80% of patients with clinical stage I or II and 23% with clinical stage III malignant pleural mesothelioma.[45] Lymph node disease and biphasic/sarcomatoid histology have classically been associated with poorer survival in the majority of surgical series with recurrences occurring chiefly locally after pleurectomy decortication procedures and systemic recurrences after EPP.[46] The role of surgery for diagnostic biopsies confirming sarcomatoid disease is controversial. The 2018 ASCO Guidelines do not recommend maximal surgical cytoreduction for known sarcomatoid histology based on intermediate-quality evidence,[47] whereas the 2019 National Comprehensive Cancer Network guidelines state that surgery in patients with sarcomatoid or mixed histology should only be reserved for those with early-stage, minimally bulky disease without lymph node involvement.[48] Perhaps, the best compromise is that recommended by the International Association for the Study of Lung Cancer Mesothelioma Committee, which advises that patients with sarcomatoid histology should be offered clinical trials considering their poor outcome.[39]

Novel research approaches include the use of preoperative radiation therapy before EPP have had encouraging results in a subgroup of patients with epithelioid histology and no involved lymph nodes at resection with a median overall survival of 66 months; however, the overall median survival of 24 months remains soberingly similar to results from other trials in the literature.[49] Additional novel approaches that are just beginning to be reported include the use of dual checkpoint induction therapy followed by resection, include intriguing data regarding the tumor microenvironment and response to therapy (NCT02592551). Finally, standardization of reporting of procedures in the future will hopefully help define which procedure provides the maximum of benefit and minimum of morbidity for each individual patient.[50]