Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that arises from the lining mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. Morbidity and mortality are almost entirely due to disease progression within the peritoneum and not distant metastatic spread.
General treatment principles and historic evolution
There is no consensus as to the optimal treatment for MPM. Due to the rarity of this entity, most of the available clinical information about treatment has been derived from retrospective single-center series, which have inherent selection biases. Prospective clinical trials are few and small, and there are currently no randomized studies that compare one treatment with another.
MPM is quite heterogeneous in clinical behavior (particularly between men and women). There are many prognostic variables, some of which are only assessable at surgical evaluation. The different histologic types have different natural histories; the sarcomatoid or biphasic subtype has a worse prognosis than the more common epithelial subtype, and there are two variants, both of which arise predominantly in women, that are associated with indolent clinical behavior.
Candidates for cytoreductive surgery
For selected patients with diffuse MPM, no extraperitoneal disease spread, a good performance status, and who can be predicted to achieve complete surgical cytoreduction based on initial radiographic imaging we recommend regional therapy using cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal perfusion with chemotherapy (HIPEC) rather than systemic or intraperitoneal chemotherapy or debulking surgery alone.
Potential candidates for CRS/HIPEC should be referred to and treated in a center with expertise in the management of peritoneal surface malignancies.
The role of adjuvant or neoadjuvant systemic chemotherapy in conjunction with CRS plus HIPEC is uncertain, and there is no consensus as to the best approach. For patients in whom the timing of operative CRS and HIPEC must be delayed, we suggest a course of systemic chemotherapy until the definitive operation can be performed.
Following CRS/HIPEC, for those patients whose tumors display high-risk features (eg, the presence of deep tissue invasion, biphasic histology, baseline thrombocytosis), we suggest a course of systemic chemotherapy as consolidation. For patients with optimal cytoreduction and no histopathologic features that would suggest increased risk of early recurrence, we would not pursue systemic therapy.
Not candidates for cytoreductive surgery
For patients who are not candidates for CRS/HIPEC, we suggest systemic chemotherapy rather than debulking surgery with or without chemotherapy. When the chemotherapy regimen includes pemetrexed, concurrent supplementation with vitamin B12 and folic acid is needed to reduce toxicity.
The role of immunotherapy is evolving. In our view, the available data are insufficient to conclude that immunotherapy using a checkpoint inhibitor alone or in combination (ie, ipilimumab plus nivolumab) should be considered as a first-line treatment option for MPM. However, checkpoint inhibitor immunotherapy may be a reasonable option for second-line therapy and beyond.
All patients with peritoneal mesothelioma should be referred for germline testing given the high frequency of mutations in inherited cancer susceptibility genes in this disease; testing may reveal deficiency in mismatch repair (dMMR), which might predict benefit from pembrolizumab
References
• Sugarbaker PH, Welch LS, Mohamed F, Glehen O. A review of peritoneal mesothelioma at the Washington Cancer Institute. Surg Oncol Clin N Am 2003; 12:605.
• Panou V, Gadiraju M, Wolin A, et al. Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma. J Clin Oncol 2018; 36:2863.
• White MG, Schulte JJ, Xue L, et al. Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy. Br J Cancer 2021; 124:564.
• https://www.uptodate.com/contents/malignant-peritoneal-mesothelioma-treatment?