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 relatively prolonged survival.
Data supporting treatment recommendations are derived from observational studies. The benefits of incorporating surgery and radiation therapy into the initial treatment 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".)
INITIAL EVALUATION AND CLINICAL APPROACH — 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'.)
Diagnosis and staging — 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 these 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'.)
Clinical approach — A multidisciplinary treatment plan is based upon the assessment of the extent of disease, the patient's overall condition including cardiopulmonary function and other comorbidities, and their desire for aggressive treatment. Chemotherapy with pemetrexed plus a platinum compound (cisplatin or carboplatin) is the standard approach for MPM, but approximately 20 percent of patients with MPM may be candidates for surgery with a macroscopic complete resection (MCR; ie, an R0 or R1 resection) as part of a combined-modality approach [1]. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'First-line treatment'.)
Whether resection as part of a combined-modality approach actually improves survival is uncertain and has not been established in a prospective randomized trial. 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' below.)
●Surgical candidates – For patients who have surgically resectable disease limited to one hemithorax and have no medical contraindication to surgery, we use a combined-modality approach that incorporates surgery aimed at MCR with chemotherapy and/or radiation therapy. (See 'Surgery-based therapy' below.)
●Nonsurgical candidates – 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 chemotherapy and/or symptom-directed treatment may be beneficial. (See 'Nonsurgical approaches' below.)
SURGERY-BASED THERAPY — A combined-modality approach is often used in patients with a surgically resectable tumor when there is access to a center with adequate expertise in all aspects of the management of MPM. Therapy in this setting includes a definitive surgical procedure (extrapleural pneumonectomy [EPP] or pleurectomy/decortication [P/D]), combined with radiation therapy (RT) to enhance local disease control and chemotherapy (systemic, either preoperative or postoperative, or intraoperative) to reduce the risk of local recurrence and systemic metastases. (See 'Patient selection' below.)
Although an overall survival (OS) advantage has not been demonstrated with these approaches in randomized trials, this approach has been associated with relatively prolonged survival compared with chemotherapy alone for patients in contemporary surgery-based series. (See 'Surgery' below and 'Radiation therapy' below.)
Patient selection — Although surgery is not considered the standard-of-care treatment for MPM, there seem to be patients who benefit from a surgery-based approach beyond what would otherwise be expected. These aggressive procedures should be limited to surgeons and centers with appropriate expertise in these procedures and in the management of MPM. Identifying the subset of patients who might be good surgical candidates is an area of active research.
Many surgeons consider histologic subtype the single most important oncologic selection criterion, although it is not part of the staging system, and thus they only offer surgery-based treatment to patients with epithelial subtype. The histologic subtype should be established with a biopsy, not cytology, since other cell types are not typically shed into the pleural fluid. Across nearly all surgical series, the benefit of surgery appears to be limited to patients with pure epithelial subtype. Patients with mixed or pure sarcomatous variants often have OS that are the same or shorter than what would be expected with nonoperative therapy [2].
Other factors associated with a worse prognosis for surgery include age >50 years, male gender, platelet count >400,000/microL, or white blood cell count >15,000/microL [2,3]. Chest wall pain at presentation is a worrisome feature that prevents many experienced surgeons from attempting surgery. Tumor volume, as measured by computed tomography, is also associated with a worse prognosis [4]. The common variable here seems to be the bulk of solid tumor on presentation; although increased tumor bulk may have a negative impact on survival, it does not preclude a successful macroscopic complete resection (MCR) with reasonable OS in the context of a multimodality approach.
Given the morbidity and potential mortality associated with surgery, the use of EPP or a lung-sparing P/D procedure should be limited to situations in which surgery will result in a complete resection of all gross tumor. 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. Whether pleurodesis prior to surgery makes subsequent surgery more difficult or whether it may actually facilitate resection is controversial. (See 'Pleural effusions' below.)
Assessment of patient-specific factors by an experienced surgeon will be required to determine the appropriate procedure for each individual patient. An experienced surgeon generally will not knowingly explore a patient for "palliation," and most so-called palliative mesothelioma resections are the result of a failed attempt at an MCR.
Patient-specific factors that need to be considered include the following:
●There should be no imaging evidence of disseminated disease outside the involved hemithorax (clinical stage I to III) (table 1).
●The patient should have adequate cardiopulmonary function such that he/she will be able to tolerate the procedure.
●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.
Surgical procedure nomenclature — There has been considerable variability in the nomenclature used to describe MCR procedures. Based upon a survey of surgeons experienced with surgical management of MPM, the Mesothelioma Domain of the International Association for the Study of Lung Cancer recommended the following uniform definitions for MPM resections [5]:
●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.
●Extended P/D – Parietal and visceral pleurectomy to remove all gross tumor with resection of the diaphragm and/or pericardium.
●P/D – Parietal and visceral pleurectomy to remove all gross tumor without diaphragm or pericardial resection.
●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.
Surgery — The role of definitive surgery (MCR; ie, an R0 or R1 resection) for MPM is controversial. Whether resection actually is responsible for an improvement in survival in some patients is uncertain and has not been established in a prospective randomized trial. When surgery is undertaken, the goal should be the removal of all visible or palpable tumor, regardless of whether that involves EPP or a lung-preserving operation (P/D).
MCR procedures are associated with substantial morbidity and potential mortality. Early reports using EPP reported mortality rates as high as 31 percent [6]. However, subsequent studies, which relied upon improved strict functional criteria for patient selection, as well as improvement in techniques, have resulted in mortality rates less than 5 percent. Despite careful selection of the patients who are to undergo MCR, there are no prognostic predictors that accurately determine which patients will recur rapidly after surgery and therefore derive no benefit.
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). In combining these three modalities, chemotherapy has been given both prior to surgery [7,8] and as an adjuvant following surgery [9]. Lung-sparing procedures (P/D) have also been combined with chemotherapy and RT. (See 'Chemotherapy' below.)
For patients who are candidates for MCR, the optimal procedure to be performed (ie, EPP versus P/D) is uncertain, and there are no data from randomized trials comparing different approaches. In addition, there are no randomized trials that define the optimal approach for the integration of other modalities (chemotherapy, RT) before and/or after surgery.
Extrapleural pneumonectomy (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.
Contemporary, large, retrospective series from high-volume centers have reported median survivals of approximately 18 months for patients whose treatment included EPP as part of a combined-modality approach [10-12]. 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 [10]. 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 [13].
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 [14]. 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.
Pleurectomy/decortication (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.
EPP versus P/D — The choice of a specific 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. There are no randomized trials that compare EPP versus P/D, but retrospective analyses suggest that survival outcomes are similar.
The most extensive data comparing EPP versus P/D come from a retrospective review of 663 consecutive patients who underwent surgery at three mesothelioma centers in the United States [15]. The operative mortality was greater for EPP than for P/D (27 of 385 [7 percent] versus 13 of 278 [4 percent]). EPP was associated with a worse OS (median 12 versus 16 months); this difference was statistically significant on multivariate analysis controlling for histology, stage, gender, and use of multimodality therapy. When the data were analyzed based upon clinical stage, there was no statistically significant difference for any stage. This study was the first to postulate that patients who underwent P/D could have comparable survival with those who underwent EPP; however, the reasons for such a conclusion were multifactorial and subject to selection bias. The morbidity and mortality conclusions from this study have been validated by a study from the Society of Thoracic Surgeons Database [16].
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 to EPP. Contemporary studies, however, have shown that satisfactory morbidity and mortality can be achieved after induction therapy with EPP [17].
Radiation therapy — The pattern of spread of MPM poses unique challenges to a radiation oncologist. Since the disease most often is confined to the ipsilateral pleura, local control is the primary 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. RT may also be used prophylactically to chest wall intervention sites. (See 'Tumor seeding at the instrumented site' below.)
Although the data using RT following surgery with either EPP or P/D suggest that RT improves local control, the available data from retrospective series do not suggest that there is a significant improvement in OS (table 4).
RT after EPP — Advances in radiation therapy (RT) techniques have led to the widespread application of highly conformal, three-dimensional techniques, such as intensity-modulated RT (IMRT), in patients with MPM having extrapleural pneumonectomy (EPP). (See "Radiation therapy techniques in cancer treatment".)
Historically, adjuvant RT after EPP was given through anterior and posterior fields that encompassed the entire involved hemithorax. This simple approach has the advantage of avoiding oblique angles that could expose the contralateral lung to low doses of radiation. Sparing of organs in the RT field (eg, heart, liver, kidneys, or stomach) is achieved by blocking those areas and adding an electron boost to the anterior and posterior chest wall to compensate for the missing dose. This invariably leads to dose uncertainties along the edges of blocked areas as well as under- and overdosing of the pleural space and chest wall. Also, tolerance limits require blocking the spine after 4140 cGy, often leading to underdosing of the medial pleura and mediastinum/hilum [18].
A phase II trial exploring high-dose hemithoracic RT to 54 Gy following EPP demonstrated high rates of local control, with only two isolated locoregional failures in 54 patients and a median survival of 17 months [19] (stage I and II tumors, 33.8 months; stage III or IV, 10 months). Multiple subsequent studies incorporated this technique into a multimodality approach combining chemotherapy, EPP, and hemithoracic radiation [7,20-22].
However, with conventional RT there may be radiation underdosing near regions that are blocked. This has the potential to lead to increased risk of local failure in approximately 10 to 15 percent of patients [23].
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 [24]. Areas of potential under- or overdosing are readily recognizable in the planning phase and thus can be corrected.
A potential disadvantage of IMRT is the dose of radiation delivered to the contralateral lung, which increases the risk of pneumonitis. Several groups reported significantly increased toxicity and even deaths from radiation pneumonitis in patients treated with IMRT after EPP [25-27]. 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 [26-28]. Strict dosimetric guidelines, particularly on the contralateral lung, are therefore critical. Increasing experience with IMRT has led to improved target coverage and has decreased rates of toxicity [28-31].
RT after P/D — The use of IMRT and related contemporary three-dimensional conformal radiation therapy (RT) techniques in conjunction with pleurectomy/decortication (P/D) is expanding in an effort to improve local control while minimizing toxicity [32-35].
Older approaches using two-dimensional (anterior-posterior) techniques were limited since the ipsilateral lung remained in situ after P/D. Even though blocks were used to protect the heart and central part of the lungs and an electron field was added to boost the dose, this technique resulted in a disappointing one-year local control rate of 42 percent and a median survival of 13.5 months [23].
The results using IMRT are illustrated by the single-institution experience in 67 patients with two intact lungs treated at the Memorial Sloan Kettering Cancer Center between 2004 and 2013 [32,35]. In this cohort, 42 patients (63 percent) underwent P/D prior to RT, while 25 (37 percent) were unresectable and underwent definitive hemithoracic pleural IMRT. Median follow-up was 24 months. Treatment was delivered in 1.8 Gy fractions to a total dose of 50.4 Gy [32]. The one- and two-year OS rates were 85 and 50 percent, respectively.
A pattern of failure analysis in patients who had undergone P/D found that the majority of local failures occurred in sites of gross disease, supporting the role of a macroscopically complete surgical resection when feasible [35]. Local (in field) failure occurred in 43 cases (64 percent), and 32 of these (74 percent) occurred at sites of previous gross disease. Furthermore, when patients who had been treated with P/D followed by IMRT were compared with those treated with IMRT alone, there was a significantly prolonged time to in-field recurrence (14 versus 6 months).
In a two-center phase II study evaluating pleural IMRT with chemotherapy after 27 patients received radiation after chemotherapy and P/D (median dose, 46.8 Gy) [36]. Eight patients had grade 2 or 3 pneumonitis. The median progression-free survival and OS were 12.4 and 23.7 months, respectively. The two-year OS was 59 percent in patients with resectable tumors and 25 percent in patients with unresectable tumors. A follow-up retrospective study suggested that outcome was better with pleural IMRT as compared with conventional techniques [37]. Based on the prior studies, the NRG-LU006 trial is a potential practice-changing phase III trial that randomizes 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.
A study of radiation-related toxicity suggested that heart dose may be an important factor in whether a patient develops symptoms of pneumonitis [38]. 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.
RT before EPP — A novel treatment technique of delivering accelerated hemithoracic radiation followed by extrapleural pneumonectomy (EPP) has been investigated [39]. Patients receive 25 to 30 Gy of IMRT to the entire hemithorax one week prior to EPP. Treatment has been well tolerated with only one treatment-related death amongst 62 patients, and there was a median survival of 36 months.
Chemotherapy — Even if disease can be controlled locally with surgery and/or RT, most patients develop systemic metastases. Combinations of active agents, such as cisplatin plus pemetrexed, have been shown to prolong OS in patients with unresectable disease and have therefore also been integrated into combined-modality approaches with surgery and/or RT for those with resectable disease. In these regimens, chemotherapy has been given both prior to surgery [7,8] and as an adjuvant following surgery [9]. Choice of chemotherapy is usually pemetrexed and a platinum agent (table 5 and table 6), as is commonly administered for those with unresectable disease. (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'.)
The feasibility of integrating neoadjuvant chemotherapy with surgery and RT was illustrated by a multicenter phase II study [7]. In this trial, 77 patients were treated with neoadjuvant pemetrexed plus cisplatin, which was to be followed by EPP and then adjuvant RT. Overall, EPP was attempted in 57 patients and completed in 54, while radiation was initiated in 44 cases and was able to be completed in 40 patients. The median OS for the entire cohort was 17 months. For those who were able to complete chemotherapy, surgery, and RT, median survival was 29 months, with a 61 percent two-year survival rate.
In addition, intraoperative intracavitary chemotherapy has been studied in an effort to improve local disease control. In a series of 92 patients, hyperthermic intracavitary perfusion with cisplatin (225 mg/m2) was performed following EPP [40]. Recurrence of pleural mesothelioma was seen in 47 patients (51 percent) and was ipsilateral in 16 cases (17 percent). Intracavitary chemotherapy remains experimental and should be limited to formal clinical studies.
Randomized trials — There are no adequately powered randomized trials that have defined the benefit of combining surgery using an MCR with chemotherapy and RT in patients with localized MPM.
Although the Mesothelioma and Radical Surgery trial was originally designed with adequate statistical power to assess the role of EPP, accrual difficulties led to its transformation into a feasibility study. In the feasibility trial, 112 patients were treated with induction chemotherapy. Subsequently, 50 patients were randomly assigned to EPP or no EPP, which was to be followed by RT [41]. There were no statistically significant differences in survival at 6, 12, or 18 months, and median survivals for EPP and no EPP were 14.4 and 19.5 months, respectively.
The authors concluded that combined-modality therapy did not offer any benefit. However, the study was severely underpowered to detect any difference between the two treatment approaches, 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 single-institution phase II studies, and there were several other issues in the conduct of the trial that compromise any conclusions.
As a result of this trial and the interest in lung preservation in mesothelioma, a randomized trial comparing radical pleurectomy with photodynamic therapy and postoperative chemotherapy to radical pleurectomy with postoperative chemotherapy will be initiated at University of Pennsylvania (NCT02153229). In Europe, plans for a comparison of preoperative versus postoperative chemotherapy with lung-sparing surgery for mesothelioma are being formulated.
NONSURGICAL APPROACHES — Many patients with localized 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.
Pleural effusions — 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 such effusions recur relatively rapidly, and a more definitive procedure may be required.
Multiple approaches have been used to manage such effusions. (See "Management of malignant pleural effusions", section on 'Initial treatment'.):
●Pleurodesis – Pleurodesis can often control symptoms from pleural effusions by obliterating the pleural space and causing adhesions between the visceral and parietal pleura. Complete drainage of the pleural effusion by tube thoracostomy or video thoracoscopy followed by introduction of an irritative agent into the pleural space to produce pleural symphysis or obliteration of the pleural space often provides palliation in this setting.
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 [42]. 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)'.)
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. The patient's options must be considered, and if the patient is a candidate for nonsurgical catheter-based intrapleural therapies, symphysis of the pleura may not be desired.
●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. (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 OS 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 [43]. VATS pleurectomy has not been directly compared with the use of indwelling valved catheters. (See "Management of malignant pleural effusions", section on 'Pleurectomy'.)
Tumor seeding at the instrumented site — 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 [44]. Given the sum of the data, prophylactic RT is not standard of care for those undergoing limited 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 6 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) [45]. 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 [46,47].
However, in an earlier small trial, RT appeared to reduce recurrences [48]. In this trial, 40 patients who had had invasive diagnostic procedures (cytology, needle biopsy, thoracoscopy, or chest tube placement) were randomly assigned to either 21 Gy in three fractions or no treatment. There were no chest wall recurrences in the RT patients but a 40 percent incidence in the patients who did not receive treatment, a difference that was statistically significant.
Since the majority of studies found no advantage of RT to decrease seeding at surgical sites, we do not suggest it for this indication.
Systemic therapy — For patients who cannot tolerate aggressive trimodality therapy, combination chemotherapy with a platinum-based doublet such as cisplatin plus pemetrexed, with or without bevacizumab, has been shown to prolong survival in patients with unresectable MPM. The combination of nivolumab plus ipilimumab has also been shown to improve survival in those with unresectable disease, particularly for those with nonepithelioid histology. (See "Systemic treatment for unresectable malignant pleural mesothelioma".)
Radiation therapy — There are only limited data available on the role of RT in combination with systemic therapy in patients with two intact lungs who are not candidates for extrapleural pneumonectomy or P/D. At least one report has reported that this approach is feasible using IMRT [32,34], but additional study is required.
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The COVID-19 pandemic has increased the complexity of cancer care. Important issues include balancing the risk from treatment delay versus harm from COVID-19, ways to minimize negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited health care resources. These and recommendations for cancer care during active phases of the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)
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
●Patients with malignant pleural mesothelioma (MPM) generally present with locally extensive disease. Surgery, radiation therapy (RT), and systemic chemotherapy each may be beneficial as single modalities in selected situations, but the prognosis for prolonged survival is poor. (See "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma", section on 'Prognosis'.)
●For patients with 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 'Patient selection' above.)
●For surgical candidates, we suggest a combined-modality approach that includes chemotherapy (generally a platinum plus pemetrexed (table 5 and table 6)), surgery (MCR) with either pleurectomy/decortication or radical extrapleural pneumonectomy, and RT. (Grade 2C). Although this approach has not been demonstrated to improve overall survival in randomized trials, carefully selected patients may have relatively prolonged survival. (See 'Surgery-based therapy' above.)
●For patients who are not surgical candidates, management of symptoms from any pleural effusion, systemic chemotherapy, and palliative RT may all have a role. (See 'Nonsurgical approaches' above and "Management of malignant pleural effusions" and "Systemic treatment for unresectable malignant pleural mesothelioma".)
