Version May 2024
INTRODUCTION — Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from the mesothelial surfaces of the pleural cavity. Mesotheliomas may also arise from the peritoneal surface, the tunica vaginalis, or pericardium.
MPM has a poor prognosis. The median survival of patients is between 6 and 18 months, and the outlook has not been substantially improved by newer therapeutic interventions. However, carefully selected patients with localized disease who receive aggressive multimodality therapy have experienced relatively prolonged survival.
Data supporting treatment recommendations are largely derived from observational studies. The benefits of incorporating surgery and radiation therapy into the initial treatment of MPM have not been demonstrated in randomized trials.
The initial management of patients with MPM is reviewed here. Other related topics include:
●(See "Systemic treatment for unresectable malignant pleural mesothelioma".)
●(See "Epidemiology of malignant pleural mesothelioma".)
●(See "Pathology of malignant pleural mesothelioma".)
●(See "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma".)
CLINICAL MANIFESTATIONS, DIAGNOSIS, AND STAGING — Most patients with MPM present with the gradual onset of pulmonary symptoms (dyspnea, cough, chest pain). Symptoms generally are present only once extensive intrathoracic disease has developed. (See "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma", section on 'Clinical manifestations'.)
Clinical suspicion for MPM may arise in the setting of respiratory symptoms in the context of pleural thickening or an effusion on chest imaging and a history of asbestos exposure.
Although clinical features may raise the suspicion of MPM, a biopsy is necessary to confirm the diagnosis. The initial evaluation, diagnosis, and staging of MPM are discussed elsewhere. (See "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma", section on 'Diagnosis' and "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma", section on 'Staging and pretreatment evaluation'.)
GENERAL PRINCIPLES OF MANAGEMENT
Establishing histology — The histologic subtype should be established with a biopsy, not cytology, since cells from sarcomatoid mesotheliomas are not typically shed into the pleural fluid.
The histologic subtype is often considered to be the important oncologic selection criterion for surgery. Across nearly all surgical series, the benefit of surgery appears to be limited to patients with pure epithelial subtype. (See 'Epithelioid cancers' below.)
Surgery in patients with nonepithelioid cancers (eg, mixed or pure sarcomatous variants) has failed to demonstrate overall survival benefits relative to nonoperative therapy. (See 'Nonepithelioid cancers' below.)
Management of pleural effusions — Many patients with pleural mesothelioma will present with a pleural effusion. Large pleural effusions can cause persistent dyspnea, which, along with pain, is the most common symptom in patients with MPM. Although dyspnea can be relieved by thoracentesis, most effusions recur relatively rapidly, and a more definitive procedure may be required. Multiple approaches have been used to manage such effusions, including pleurodesis, tunneled catheters, or video assisted thoracoscopic subtotal (VATS) pleurectomy.
●Pleurodesis – Pleurodesis can often control symptoms from pleural effusions by obliterating the pleural space and causing adhesions between the visceral and parietal pleura. However, pleurodesis may not be the optimal approach to a pleural effusion in patients who present with MPM that is mainly effusive and do not have much bulky disease. If such patients are candidates for nonsurgical catheter-based intrapleural therapies, those may be preferable.
In patients in whom pleurodesis is chosen, complete drainage of the pleural effusion by tube thoracostomy or video thoracoscopy followed by introduction of an irritative agent into the pleural space produces pleural symphysis or obliteration of the pleural space. This often provides palliation in this setting. Whether pleurodesis makes subsequent surgery (if indicated) more difficult or whether it may actually facilitate resection is controversial. (See 'Surgical candidates' below.)
The most widely used compound for pleurodesis is sterile, asbestos-free talc, either insufflated as a powder or instilled via chest tube as a slurry [1]. However, the presence of bulky tumor in the pleural space or a thick visceral pleural peel of tumor can preclude successful pleurodesis because the lung may not completely expand to allow for visceral and parietal pleural contact. Talc should not be used as a sclerosant unless the lung fully expands; talc is a permanent foreign body, which can serve as a nidus for an intractable empyema if the residual pleural space (due to the lung entrapment) gets infected. (See "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)'.)
●Tunneled catheters – Some patients with entrapped lungs and sizable effusions can get relief from a tunneled catheter even though the lung does not expand. The mechanism of this may be relieving pressure on the diaphragm. Patients may report an improvement in their breathing, decreased pain, and/or an improvement in early satiety. Unfortunately, the use of these catheters has been associated with local subcutaneous or muscular disease invasion at the entry sites. (See "Management of malignant pleural effusions", section on 'Indwelling pleural catheter (IPC)'.)
●VATS pleurectomy – Video assisted thoracoscopic subtotal (VATS) pleurectomy may also have a role in the palliative management of pleural effusions in patients with MPM. However, VATS pleurectomy does not improve overall survival in patients with MPM. In the randomized MesoVATS trial, VATS pleurectomy provided better control of pleural effusion at one and six months, but not at 3 and 12 months compared with pleurodesis [2]. VATS pleurectomy has not been directly compared with the use of indwelling valved catheters. (See "Management of malignant pleural effusions", section on 'Pleurectomy'.)
Treatment of the malignancy — A multidisciplinary treatment plan is based upon the assessment of the extent of disease and histology, the patient's overall condition including cardiopulmonary function and other comorbidities, and their desire for aggressive treatment. A general framework is presented below.
●Stage I to IIIA epithelioid cancers – For patients with stage I to IIIA epithelioid histology cancers who have no medical contraindication to surgery, we use a combined-modality approach that incorporates surgery aimed at macroscopic complete resection (MCR), with systemic therapy and/or radiation therapy; however, systemic therapy alone is a reasonable alternative. Approximately 20 percent of patients with MPM may be candidates for surgery with an MCR (ie, an R0 or R1 resection) [3]. These patients should be managed at a center with adequate expertise in all aspects of the management of MPM. (See 'Epithelioid cancers' below.)
Whether resection as part of a combined-modality approach actually improves survival is uncertain. The controversial MARS2 randomized trial did not demonstrate a benefit with preoperative chemotherapy, surgery, and postoperative chemotherapy versus chemotherapy alone; these data have been reported in a conference abstract, but full publication of the data is awaited. (See 'Surgical candidates' below.)
If surgery is to be used as part of the initial treatment, the goal is an MCR, regardless of the specific surgical approach (lung sparing versus lung sacrificing). (See 'Patient selection and rationale for surgery' below.)
●Other cancers – The majority of patients will be treated with systemic therapy. This includes patients with sarcomatoid or biphasic histology (of any stage) and clinical stage IIIB to IV epithelioid cancers. Additionally, for patients who have disease in which an MCR is not feasible and for those who are not candidates for definitive surgery because of age, inadequate cardiopulmonary reserve, or other comorbidities, systemic therapy is used, and/or symptom-directed treatment. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'First-line treatment'.)
NONEPITHELIOID CANCERS
Systemic therapy preferred over other modalities — For patients with nonepithelioid cancers, surgery has not shown clinically significant benefit in studies to date [4], and as such, systemic therapy with a goal to extend survival and improve symptoms is a key aspect of treatment. Palliative radiation may also be used to alleviate pain or other symptoms.
The combination of nivolumab plus ipilimumab has also been shown to improve survival in those with unresectable disease, particularly for those with nonepithelioid histology [5], as discussed elsewhere. (See "Systemic treatment for unresectable malignant pleural mesothelioma".)
Trials are underway to evaluate the role of surgery with immunotherapies with and without radiation and with and without chemotherapy.
There are only limited data available on the role of radiation therapy (RT) in combination with systemic therapy in patients with two intact lungs who are not candidates for extrapleural pneumonectomy or pleurectomy/decortication. At least one report has reported that this approach is feasible using intensity modulated RT [6,7], but additional study is required prior to routine clinical use.
EPITHELIOID CANCERS
Approach — Although surgery is not appropriate for many patients with MPM, a subset of patients with epithelioid cancers may derive benefit from surgery. Data addressing this question are evolving. These aggressive procedures should be limited to surgeons and centers with appropriate expertise in these procedures and in the management of MPM, and systemic therapy alone should be considered a reasonable alternative.
Patient selection and rationale for surgery — Assessment of operability begins with drainage of a pleural effusion, if present, in order to improve dyspnea or cough and to assess the extent of disease. (See 'Management of pleural effusions' above.)
For patients with epithelioid histology cancers who have surgically resectable disease limited to one hemithorax (stage I to IIIA) and have no medical contraindications to surgery, we use a combined-modality approach that incorporates surgery aimed at macroscopic complete resection (MCR). Given the morbidity and potential mortality associated with surgery, it should be limited to situations in which surgery will result in a complete resection of all gross tumor; even in such situations, patients should be advised that systemic therapy without surgery is a reasonable alternative, given the lack of a clearly demonstrated improvement in survival. We do not pursue surgical exploration for palliation; in practice, most so-called palliative mesothelioma resections are the result of a failed attempt at an MCR.
Patient-specific factors that need to be considered in determining candidacy for surgery include the following:
●There should be no imaging evidence of disseminated disease outside the involved hemithorax (clinical stage I to IIIA) (table 1). Options for imaging include positron emission tomography with computed tomography (PET-CT) or CT.
•PET-CT has high accuracy when performed prior to pleurodesis and can detect occult distant metastases missed on CT scans. Moreover, nodal category has been found to be concordant to surgical histopathology in 63 percent of patients having surgery [8]. However, CT scanning can also estimate volume of disease for prognosis [9-12]. Pleural thickness measurements, best taken at three points on the CT scan, contribute to staging and prognostic accuracy [13-16].
●The patient should have adequate cardiopulmonary function such that they will be able to tolerate the procedure. Assessments should include electrocardiogram, echocardiogram, and pulmonary function tests prior to any surgery.
●The patient should have no serious comorbidity, and patients with an Eastern Cooperative Oncology Group performance status 2 or worse are generally excluded.
●Patients need to be fully informed that there is no uniformly accepted standard of care for MPM and that a surgery-based approach is only one option; expert consultation should be obtained if available.
Although the following are not contraindications to surgery, factors associated with a worse prognosis include:
●Age >50 years.
●Male sex.
●Platelet count >400,000/microL, or white blood cell count >15,000/microL [4,17].
●Persistent chest wall pain requiring narcotics for relief, which is a concerning feature for chest wall invasion. Further imaging may be used to exclude this prior to surgery.
●Tumor volume, as measured by CT, is also associated with a worse prognosis [18]. Although increased tumor bulk may have a negative impact on survival, it does not preclude a successful MCR with reasonable overall survival (OS) in the context of a multimodality approach.
Although an OS advantage has not been demonstrated with surgery in randomized trials, this multidisciplinary approach has been associated with relatively prolonged survival compared with chemotherapy alone for patients in contemporary surgery-based series (table 2).
Trials evaluating the role of surgery have not demonstrated a survival benefit with surgery but have significant limitations.
●In the Mesothelioma and Radical Surgery trial, 50 patients who completed neoadjuvant chemotherapy were randomly assigned to extrapleural pneumonectomy (EPP) or no EPP, followed by radiation therapy (RT) [19]. Although there were no statistically significant differences in survival (median survivals for EPP and no EPP were 14.4 and 19.5 months, respectively), the study was severely underpowered to detect any differences, with an original power calculation indicating that 670 patients would be required. Furthermore, the operative mortality was 18 percent, compared with 3 percent in contemporary studies (table 2).
●In the MARS 2 trial, presented as an abstract only, among 335 patients with resectable mesothelioma, OS was better with chemotherapy alone compared with an approach including both chemotherapy and surgery. All patients in this trial received two cycles of chemotherapy with a platinum agent and pemetrexed. After a CT scan to assess resectability, patients were randomly assigned to receive up to four cycles of the same chemotherapy alone or after surgery. At 42 months after randomization, chemotherapy alone improved OS relative to preoperative chemotherapy, surgery, and postoperative chemotherapy (hazard ratio [HR] 1.28, 95% CI 1.02-1.60). The surgery arm experienced a 4 percent 30-day and 9 percent 90-day mortality rate and 3.6 times higher chance of grade ≥3 adverse events.
Limitations of the trial, however, include questions regarding choice of patients as "surgical candidates," the preoperative metastatic workup, and randomization. As an example, in the surgery arm, there were more patients with sarcomatoid tumors and patients with tumor extension to the pulmonary parenchyma, but fewer patients with diaphragmatic muscle involvement. We await full reporting of this trial prior to refining our approach.
Surgical candidates
Types of surgical procedures — Once the decision has been made to proceed with surgery, assessment of patient-specific factors by an experienced surgeon will be required to determine the appropriate procedure for each individual patient. Although there is variability in the nomenclature used to describe MCR procedures, an expert group provided the following the following uniform definitions for MPM resections [20]:
●EPP – En bloc resection of the parietal and visceral pleura with the ipsilateral lung, pericardium, and diaphragm. In cases where the pericardium and/or diaphragm are not involved by tumor, these structures may be left intact.
The following are considered lung sparing approaches:
●P/D – Parietal and visceral pleurectomy to remove all gross tumor without diaphragm or pericardial resection.
●Extended P/D – Parietal and visceral pleurectomy to remove all gross tumor with resection of the diaphragm and/or pericardium.
●Partial pleurectomy – Partial removal of parietal and/or visceral pleura for diagnostic or palliative purposes but leaving gross tumor behind when an R0 or R1 resection does not prove to be feasible.
Outcomes with EPP and P/D — Outcomes with the most common surgical procedures are described below.
●With EPP – With increasing experience and better patient selection, the morbidity and mortality associated with EPP decreased, and survival results improved at centers with adequate expertise. Whether these improved results reflect a patient selection bias, decreased mortality from the procedure, or a benefit of surgery is not clear.
Large retrospective series have reported median survivals of approximately 18 months for patients whose treatment included EPP as part of a combined-modality approach [21-23]. Long-term results are significantly worse, with 5- and 10-year survival rates of 14 and 4 percent, respectively, in one series of 529 patients [21]. In an older systematic review of the use of EPP for MPM, overall perioperative mortality rates ranged from 0 to 12 percent, and the perioperative morbidity rates ranged from 22 to 82 percent. Key factors contributing to the improved results include improvements in preoperative staging, anesthesia, resection, reconstruction, and perioperative management of procedure-related complications [24].
The morbidity associated with EPP is illustrated by a large single institution experience that included over 300 cases, in which the mortality rate was 3.4 percent [25]. The most frequent complication was reversible atrial fibrillation, which occurred in 44 percent of patients. Other causes of serious morbidity included myocardial infarction, epicarditis, pulmonary complications, thrombosis, empyema, and technical and gastrointestinal complications (2, 3, 8, 6, 2, 6, and 1 percent, respectively). Observed technical issues included herniation of the heart due to failure of the pericardial patch, herniation of abdominal contents into the pleural space secondary to dehiscence of the diaphragmatic repair, vocal cord dysfunction secondary to recurrent laryngeal nerve injury, bronchopleural fistula, empyema, and prolonged respiratory failure.
●With P/D — The morbidity and mortality with EPP led to the development of P/D as an alternative MCR procedure for carefully selected patients. In addition, P/D offers the potential to preserve lung parenchyma.
Studies presenting outcomes in patients managed with P/D are summarized in the table (table 3). In these studies, the achievement of MCR using P/D was associated with a significantly better OS compared with historical studies of palliative P/D.
Choosing between options — The choice of a specific procedure, EPP versus lung sparing procedures including P/D, is a function of the surgeon's expertise and judgment on the ability to achieve an MCR. The goal is to render the patient with no evidence of visible, palpable, or viable tumor, without resection of the lung [26].
There are no randomized trials that compare EPP versus P/D, but retrospective analyses suggest that survival outcomes are similar. A retrospective review evaluated EPP versus P/D in 663 consecutive patients who underwent surgery at three mesothelioma centers in the United States [27]. EPP was associated with a higher operative mortality than P/D (7 versus 4 percent) and a worse OS (median 12 versus 16 months), although there was no statistically significant difference when these data were analyzed by stage. This study was the first to suggest that P/D could result in similar survival as EPP.
Additional observational data from series at four other centers comparing EPP versus P/D are presented in the table (table 4). In all studies, P/D seems to have less mortality, less morbidity, and a comparable OS with EPP. Contemporary studies, however, have shown that satisfactory morbidity and mortality can be achieved after induction therapy with EPP (table 4) [28].
Rationale for and timing of systemic therapy — Even if disease can be controlled locally with surgery and/or RT, patients are at risk for systemic metastases, so a multimodality approach including systemic therapy is utilized. Combinations of a platinum agent plus pemetrexed (table 5 and table 6), have improved OS in patients with unresectable disease and therefore have also been integrated with surgery and/or RT for those with resectable epithelioid cancers. In addition, the role of neoadjuvant immunotherapy with or without chemotherapy is under evaluation in clinical trials. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Pemetrexed plus cisplatin'.)
The optimal timing of systemic therapy is controversial. We offer three to four cycles of platinum-pemetrexed and consider it appropriate to administer either before or after surgery.
In a conference presentation of a randomized phase II study (EORTC 1205) including 69 patients with resectable MPM, the two-year OS rate with surgery followed by chemotherapy was 57 percent versus 63 percent for the opposite sequence, a difference that was not statistically significant [29]. Surgical mortality for immediate surgery was 2.9 percent (1 patient) compared with 0 percent for surgery after chemotherapy. We await full reporting of this trial to further inform our approach.
In observational studies, chemotherapy has been given both prior to surgery and as an adjuvant therapy following EPP and P/D [30-32], without clear benefit for induction chemotherapy compared with immediate resection [33]. Median survivals in these reports are on the order of 16 to 20 months, but not all patients can complete all aspects of the therapy. After induction chemotherapy, EPP has been feasible in approximately 70 to 90 percent of cases in most series, and the operative mortality rates have ranged from 0 to 7 percent (table 2). The full results of the EORTC 1205 phase II, trial should give further insight regarding the timing of neoadjuvant versus adjuvant therapy [34].
Adjuvant radiation therapy — Since MPM most often is confined to the ipsilateral pleura, local control is an important concern. However, treating the entire pleura requires a large radiation field, which increases the risk of toxicity. The choice of surgical intervention (EPP versus P/D) and the clinical setting will dictate how RT is delivered.
●For patients with good performance status who undergo EPP, we suggest hemithoracic adjuvant RT to improve local control, while acknowledging that the available data from retrospective series do not suggest an improvement in OS. (See 'In patients who have undergone EPP' below.)
●For patients with good performance status who undergo P/D, we suggest hemithoracic pleural intensity modulated RT (IMRT), provided that appropriate expertise is available . If the expertise is not available, we would not advise adjuvant treatment due to the ineffectiveness of conventional techniques. (See 'In patients who have undergone P/D' below.)
In patients who have undergone EPP — For patients with good performance status who undergo EPP, we suggest hemithoracic adjuvant RT to improve local control, while acknowledging that the available data from retrospective series do not suggest an improvement in OS. The dose of radiation for adjuvant therapy following EPP should be 45 to 60 Gy in 1.8 to 2.0 Gy based on the margin status.
Historically, adjuvant RT after EPP was given through anterior and posterior fields (two-dimensional radiation) that encompassed the entire involved hemithorax. This technique led to dose uncertainties along the edges of blocked areas as well as under- and overdosing of the pleural space and chest wall which could increase the risk of local failure [35,36]. Multiple subsequent studies incorporated this technique into a multimodality approach combining chemotherapy, EPP, and hemithoracic radiation [30,37-39].
A novel treatment technique of delivering accelerated hemithoracic radiation prior to EPP has been investigated [40]. Patients receive 25 to 30 Gy of IMRT to the entire hemithorax one week prior to EPP. Early reports demonstrated that this technique was safe. A long-term report of 102 patients treated on a phase II trial showed a 50 percent risk of grade 3 or worse perioperative toxicity, although there was only one death [41]. Median OS was 24.4 months. The five-year risks of local recurrence and distant recurrence were 20 and 63 percent, respectively, with most distant recurrences taking place in the contralateral chest or peritoneal cavity. Although promising, this approach is not yet standard treatment.
IMRT has been evaluated in patients who have undergone EPP. Although early efforts reported significantly increased toxicity and even deaths from radiation pneumonitis in patients treated with IMRT after EPP [42-44], subsequent studies have demonstrated acceptable toxicity [45]. Additionally, proton radiation, a radiation technique that may allow for superior sparing of critical normal structures such as the heart, lungs, or esophagus can be an option for certain situations [46]. Further explanation of IMRT, and its use in patients who have undergone P/D, are found below. (See 'In patients who have undergone P/D' below and "Radiation therapy techniques in cancer treatment", section on 'Proton beam'.)
In patients who have undergone P/D — For patients with good performance status who undergo P/D, we suggest hemithoracic pleural intensity IMRT, provided that appropriate expertise is available. If the expertise is not available, we would not advise adjuvant treatment due to the ineffectiveness of conventional techniques.
IMRT is a highly conformal radiation technique that allows more effective sparing of normal tissues, providing an opportunity for safer, less toxic treatments and increased efficacy by enabling higher radiation doses to the tumor target. It comes with a much higher level of dosimetric control leading to better target coverage than conventional techniques [47]. Areas of potential under- or overdosing are readily recognizable in the planning phase and thus can be corrected.
A potential disadvantage of IMRT, however, is the dose of radiation delivered to the contralateral lung, which increases the risk of pneumonitis. A higher mean lung dose and the volume of lung receiving 5, 10, or 20 Gy have been associated with a greater risk for lung toxicity [43,44,48]. Strict dosimetric guidelines, particularly on the contralateral lung, are therefore critical. A study of radiation-related toxicity suggested that heart dose may be an important factor in whether a patient develops symptoms of pneumonitis [49]. In general, a mean lung dose of less than 20 Gy is preferred. The amount of heart that receives 40 Gy should ideally be below 25 percent for right-sided tumors and 35 percent for left-sided disease.
Increasing experience with IMRT has led to improved target coverage and has decreased rates of toxicity [45,48,50,51]. The use of IMRT and related contemporary three-dimensional conformal RT techniques in conjunction with P/D is expanding in an effort to improve local control while minimizing toxicity [6,7,52,53]. The results using IMRT are illustrated in a randomized trial in 180 patients, in which IMRT with 50 Gy to the surgical scar and gross residual disease improved the two-year OS rate relative to palliative RT (58 versus 28 percent; HR 0.54, 95% CI 0.31-0.95) [54]. Other retrospective data demonstrate similar survival rates with IMRT, ranging between approximately 40 and 60 percent at two years [6,53,55], also supporting improved outcomes with IMRT compared with conventional techniques [55,56].
The NRG-LU006 trial is a potential practice-changing phase III trial that randomly assigns patients with MPM who received a P/D and standard chemotherapy to adjuvant pleural IMRT versus observation. The primary endpoint is OS, and the trial is open for enrollment.
Nonsurgical candidates — Many patients with localized epithelioid MPM are not candidates for a surgically-based approach due to the extent of their disease, age, underlying comorbidities, or other factors. In these situations, systemic chemotherapy and the management of the malignant pleural effusion may prolong life or provide significant symptom palliation. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'First-line treatment' and "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Pemetrexed plus cisplatin'.)
SPECIAL CONSIDERATIONS
Role for prophylactic radiation prior to procedures? — Although some have advocated for prophylactic radiation therapy (RT) as a way to prevent tumor seeding at the site of a diagnostic or therapeutic intervention, this strategy remains controversial [57]. Given the sum of the data, we suggest not using prophylactic RT for those undergoing procedures (ie, open surgical biopsies, video-assisted thoracoscopic surgery biopsies, thoracoscopy, or chest drains) for MPM.
In a randomized trial of 375 patients with MPM in the United Kingdom, those randomly assigned to receive prophylactic RT at a dose of 21 Gy in 3 fractions within 42 days of a procedure experienced similar incidence of chest wall metastases at six months as those who did not receive postprocedure RT (3.2 versus 5.3 percent; odds ratio 0.6, 95% CI 0.17-1.86) [58]. Procedures were defined as an open surgical biopsy, video-assisted thorascopic surgery biopsy, thoracoscopy, or a chest drain. Skin toxicity was the most common adverse event with RT, occurring in over one-half of patients (although only 1 patient experienced severe dermatitis). This trial excluded patients who had an open thoracotomy (given that the resulting large scar would not be able to be covered by RT fields) or those who had undergone a needle biopsy only (as the resulting scar would not be visible at the time of randomization).
Similarly, two other randomized trials did not show a statistically significant difference in recurrence between the two arms, and the risk of chest wall recurrence without treatment ranged from 10 to 13 percent [59,60]. However, in an earlier small trial, RT appeared to reduce recurrences [61]. Since the majority of studies found no advantage of RT to decrease seeding at surgical sites, we suggest not using it for this indication.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of lung cancer" and "Society guideline links: Pleural mesothelioma".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Pleural mesothelioma (The Basics)").
SUMMARY AND RECOMMENDATIONS
●Introduction – Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from the mesothelial surfaces of the pleural cavity. The median survival is between 6 and 18 months. However, carefully selected patients with localized disease who receive aggressive multimodality therapy have relatively prolonged survival. (See 'Introduction' above.)
●General principles of management – The histologic subtype should be established with a biopsy, not cytology. The histologic subtype is often considered to be the important oncologic selection criterion for surgery. Across nearly all surgical series, the benefit of surgery appears to be limited to patients with pure epithelial subtype. (See 'Establishing histology' above.)
Options to manage pleural effusions include pleurodesis, tunneled catheters, or video assisted thoracoscopic subtotal pleurectomy. (See 'Management of pleural effusions' above.)
●Nonepithelioid histology – For patients with nonepithelioid cancers, palliative systemic therapy and radiation, and symptom management are the key aspects of treatment. The combination of nivolumab plus ipilimumab is used in those with nonepithelioid histology. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Nonepithelioid histology'.)
●Epithelioid histology – For patients with epithelioid MPM limited to one hemithorax, a detailed evaluation is indicated to assess whether disease is amenable to a macroscopic complete resection (MCR), whether there is adequate cardiopulmonary function to tolerate such a procedure, and whether there are any medical contraindications. (See 'Epithelioid cancers' above.)
For patients with epithelioid histology cancers who have surgically resectable disease limited to one hemithorax (stage I to IIIA), we suggest a combined-modality approach including surgery, chemotherapy, and adjuvant radiation rather than systemic therapy alone (Grade 2C). The goal of surgery in this setting is MCR. Systemic therapy alone is a reasonable alternative. (See 'Surgical candidates' above.)
•Choice of surgery – The choice of a specific surgical procedure, extrapleural pneumonectomy (EPP) versus pleurectomy/decortication (P/D), is a function of the surgeon's expertise and judgment on the ability to achieve an MCR with the respective approaches and multimodal treatment protocols within that institution. (See 'Types of surgical procedures' above.)
•Choice of chemotherapy – For chemotherapy choice, we suggest the combination of a platinum plus pemetrexed (table 5 and table 6) (Grade 2C). Chemotherapy may be administered in the neoadjuvant setting or adjuvant setting, as multimodality therapy. (See 'Rationale for and timing of systemic therapy' above.)
•Administration of radiation
-For patients with good performance status who undergo EPP, we suggest hemithoracic adjuvant radiation therapy (RT) to improve local control (Grade 2C), while acknowledging that the available data from retrospective series do not suggest an improvement in overall survival. (See 'In patients who have undergone EPP' above.)
-For patients with good performance status who undergo P/D, we suggest hemithoracic pleural intensity modulated RT (Grade 2C), provided that appropriate expertise is available. (See 'In patients who have undergone P/D' above.)
•Approach for patients who are not candidates for surgery – Many patients are not candidates for a surgically-based approach due to the extent of their disease, age, underlying comorbidities, or other factors. In these situations, systemic chemotherapy, palliative radiation for pain or other symptoms, and the management of the malignant pleural effusion may prolong life and/or provide significant symptom palliation. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Epithelioid histology'.)
●Special considerations – We do not use prophylactic RT for those undergoing procedures (ie, open surgical biopsies, video-assisted thoracoscopic surgery biopsies, thoracoscopy, or chest drains) for MPM, given lack of clear benefit at reducing tumor seeding.
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