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Page 2 of 12 Housman et al. J Cancer Metastasis Treat 2021;7:69 https://dx.doi.org/10.20517/2394-4722.2021.159

Despite advances in chemotherapy, radiation, and immunotherapeutic agents, MPM remains challenging to
[5]
treat with a post-treatment survival of only 15% at 5-year . When possible, surgery remains a cornerstone
[1,3]
of multimodal therapy and may improve survival . The two most common techniques are extra-pleural
pneumonectomy (EPP) and pleurectomy/decortication (P/D). In this review, we will discuss both
procedures, their outcomes, and their roles in the future treatment of this disease.

DEFINITIONS OF TERMS
Due to variations in terminology, the International Association for the Study of Lung Cancer (IASLC)
[3,6]
established a uniform set of definitions for each surgical procedure for MPM . EPP refers to an en bloc
resection of the parietal and visceral pleura with the ipsilateral lung, pericardium, and diaphragm. Extended
P/D is a parietal and visceral pleurectomy to remove all gross tumors with resection of the diaphragm
and/or pericardium. P/D is defined as a parietal and visceral pleurectomy to remove all gross tumors but
without diaphragm or pericardial resection. Finally, partial pleurectomy is a partial removal of parietal
and/or visceral pleura for diagnostic or palliative purposes but leaving gross tumor behind . While these
[6]
definitions are useful guidelines, many authors still refer to procedures differently without a universally
accepted benchmark . For example, the “radical P/D” remains a widely used term to describe full parietal
[6]
and visceral pleurectomy with or without diaphragmatic and pericardial resection . For this review, unless
[6]
otherwise specified, P/D will refer to extended pleurectomy/decortication or the equivalent radical
procedure.

SURGERY FOR MPM
Multiple studies have shown that cancer-directed procedures can contribute to longer survival [1,3,7,8] .
[9]
Unfortunately, the majority of patients with MPM do not undergo surgical resection . According to a study
of 5937 patients in the Surveillance, Epidemiology, and End Results database from 1990 to 2004, only 22% of
patients with MPM undergo cancer-directed surgery, and only 40% of patients are offered surgery at tertiary
referral centers . While a variety of factors, including fitness for surgery, likely contribute to this finding, it
[9]
underscores the reality that most patients with MPM are not receiving all available therapy.

Additionally, both EPP and P/D are often described as being performed with “curative-intent”. This term
can be misleading and should only be used to differentiate therapeutic surgery from procedures that are
purely diagnostic or palliative (e.g., exploration, pleural biopsy, or partial P/D). The goal of cancer-directed
intervention should be the removal of all gross disease, which is referred to as an R1 or macroscopic
[10]
complete resection (MCR) . True R0 resection is theoretically impossible with either procedure due to the
inability to achieve surgical margins or eliminate microscopic disease [3,10-14] . One study reported that
following “macroscopic complete resection” with EPP, 70% of specimens were found to have positive
[15]
margins on final pathlogy . As a result, any cytoreductive procedure for MPM must be supplemented with
chemotherapy and/or radiation to attempt to control residual microscopic disease [1,13,16] .

EXTRA-PLEURAL PNEUMONECTOMY
The EPP was first described by Sarot in 1949 as a treatment for collapse-therapy and thoracoplasty-resistant
tuberculosis . It was first reported as a treatment for MPM in 1976 when Butchart et al. described their
[18]
[17]
experience in 29 patients with diffuse disease. Ultimately, they recommended it be used only in early-stage
disease with epithelioid histology as the “…pleuropneumonectomy does not appear materially to affect the
course of the disease in cases of mixed epithelial and mesenchymal histologic type ”.
[18]