Malignant pleural mesothelioma (MPM) is one of the most lethal cancers known to man. It is currently incurable and, therefore, all treatments, including surgery, are palliative. The cancer is typically caused by exposure to asbestos, with a lag time of 10-50 years between exposure and development of the cancer. Life expectancy is usually in the one to two year range from the time of diagnosis. Pemetrexed-platin doublet palliative chemotherapy is the current standard of care in the United States.[1] Recently there have been several advances in our knowledge of mesothelioma leading to novel systemic therapies including the addition of antiangiogenic agents such as bevacizumab and nintedamib with promising results. [2],[3],[4] There are several ongoing trials investigating immunotherapies, and other targeted therapies that may provide future benefit. Although there is currently no Level I evidence to support surgery as a treatment for MPM, there does appear to be a subset of patients who appear to benefit from an aggressive multimodal surgery-based approach than with systemic therapy alone.[5]

Selecting the patients most likely to benefit from surgery remains more art than science. Beyond the prognosticators from the staging system, which accounts for hematogenous and lymphatic metastases, some of the generally accepted factors that seem to correlate with a higher likelihood of benefit from surgery-based treatment include: epithelioid histology, less tumor bulk, no thrombocytosis, and lack of symptoms, in particular pain attributable to the cancer. Of course, any patient considered for surgery must meet all the criteria to be a safe candidate for the operation being proposed. Patients who meet this profile do appear to benefit more from a surgery-based approach than would be otherwise anticipated.[5] Additionally, the American Society of Clinical Oncology recently recommended that surgical resection be considered in select MPM patients.[6] Given that these cancers typically present with a volume of at least several hundred milliliters, often exceeding a liter, surgery is the only modality currently available that that has potential to render these patients with no evidence of disease.

Whereas it is relatively easy to make a case for surgery as a reasonable component of the treatment strategy in select patients, it is difficult to interpret the literature in a way that supports any single surgery-based treatment regimen as the optimal approach. The reasons for this are multifactorial. First, MPM is a rare cancer; there are perhaps 3000-4000 cases per year in the United States and only a small fraction of those patients undergo surgery. [7] Thus, most reports contain a relatively small numbers of patients incorporating a large number of variables. Even in the setting of statistical significance, it may be difficult to draw a convincing conclusion about the superiority of a particular approach. As opposed to lung cancer, or even the much rarer esophageal cancer, the individuals or centers with true expertise in treating MPM are by comparison, very few. Consequently, much of the available data on surgery-based treatment tends to be institution-specific techniques and protocols. Individual strategies and their outcomes may not be translatable or comparable from one surgeon to another. This is particularly true for lung-sparing surgical series, where the operative techniques and postoperative management may vary drastically from one institution to another. Interpreting results from surgery-based treatment of MPM is further confounded by a staging system that does not include some features that may be significant prognosticators of the disease when treated surgically. Great caution must be applied when trying to compare different surgery-based treatments.

Any operation for MPM, where achieving a macroscopic complete resection (MCR) and without evidence of disease is the goal, is going to be a major operation. The diffuse and infiltrative nature of MPM mandates a generous incision for exposure and meticulous attention to every square inch of the affected hemithorax. Three criteria must be met for a patient to undergo this operation – it must be safe, it must offer an oncologic benefit and the patient must understand that at this time there limited evidence supporting the use of surgery in the treatment of this cancer. It is important that the patient gives informed consent within the context of acknowledging that surgery-based treatment for mesothelioma is considered investigational and is not the standard of care.

Safety

Surgeries for MPM are major operations, regardless of the technique or approach. The patients must be of sufficiently robust health to tolerate substantial chest surgery. If pneumonectomy with or without application of an intraoperative adjuvant treatment is planned, there are additional safety criteria that will need to be met.

Oncologic Criteria

Most MPM surgeons would likely agree that exclusion criteria for surgery include: evidence of hematogenous metastases, metastatic lymph nodes outside of the ipsilateral pleural space, invasion of mediastinal structures, peritoneal dissemination, pericardial invasion, or transgression through the diaphragm into abdominal or retroperitoneal structures. Controversial, but other commonly used exclusion criteria include: bilateral disease, chest wall invasion, unusually bulky tumors, and primarily sarcomatous subtype. As there is almost certainly going to be microscopic disease remaining after even the most aggressive resections, surgery for mesothelioma should be part of a multimodal treatment plan. There is essentially no role for surgery alone for this cancer.[8],[9] Consequently, it is recommended that all MPM patients be reviewed at a multidisciplinary tumor board-type conference with the team of treating physicians prior to undergoing surgery.

Informed Consent

Despite general agreement of most MPM specialists that surgery is likely to benefit select patients, there is no Level 1 evidence supporting the role of surgery. Currently Mesothelioma and Radical Surgery 2 (MARS 2), a feasibility study, is enrolling patients. The endpoints of the study are to compare survival and quality of life in patients with malignant mesothelioma undergoing surgery versus those without surgical intervention.[10] This study may provide additional insight to the role of surgery. Thus, patients must ultimately consent for surgery in the face of known risks, but unclear benefits as the time and pattern of recurrence of MPM after surgery is unpredictable. Consequently, it is incumbent of the MPM surgeon to make this clear to patients and, in an effort to advance our understanding of this rare cancer, perform surgery in the setting of a clinical trial whenever possible.