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Page 10 of 12 Yonemura et al. J Cancer Metastasis Treat 2022;8:43 https://dx.doi.org/10.20517/2394-4722.2022.49

In our seven DMPM patients, NIPS reduced PCI from 28.1 ± 9.8 to 18.1 ± 7.4 (P = 0.008). EPIC has been
used in DMPM patients to eliminate residual micrometastasis after CRS. Recently, Sugarbaker et al. studied
the benefit of EPIC (NIPEC) on survival in 129 epithelioid DMPM patients after CRS, and the EPIC group
[12]
showed significantly better survival than the other groups .

Locoregional adjuvant NIPEC could be proposed in DMPM patients submitted to CRS + HIPEC . In our
[10]
experiences, CCR-0 resection was performed in 31% (25/81) , and CCR-0 resection rates after no
[33]
chemotherapy, NASC, and NIPS were 24% (5/21), 32% (9/28) and 34% (11/32), respectively.

The main reason for incomplete cytoreduction is diffuse involvement of the small bowel mesentery and
serosal surface. Le Roy et al. reported that bidirectional chemotherapy using IP pemetrexed and IV cisplatin
or carboplatin reduced PCI from 27 (range, 15-39) before bidirectional chemotherapy to 14 (range,
[40]
15-30) . NASC usually does not achieve sufficient downstaging to convert patients to resectability, but
bidirectional chemotherapy and NIPS + neoadjuvant LHIPEC could significantly reduce PCI on the small
bowel mesentery, resulting in an increased rate of CCR-0 rate.

CRS + HIPEC has emerged as the preferred initial treatment in selected DMPM patients, but CRS + HIPEC
carries a significant rate of grade 3/4 morbidity and mortality that range from 8% to 90% and from 1.9% to
8%, respectively [Table 2]. Accordingly, CRS + HIPEC should be performed with a strict selection of
patients by performance status, PCI levels, histologic subtype, and age [Table 2] and be confined to
specialized PSM centers.

FUTURE PERSPECTIVES
The data and results described above are from retrospective analyses. However, the efficacies of NASC,
NIPS, and postoperative chemotherapy on safety and survival after CRS + HIPEC have not been clarified.
The roles of these options should be verified by randomized clinical trials. Recent innovative treatment
modalities such as immunotherapy may constitute a breakthrough in improving the survival of DMPM
patients.

Additionally, we await the development of new molecular targeted drugs that focus on the target gene
products specific for DMPM.

CONCLUSION
Based on articles on more than 50 DMPM patients, this review analyzed the efficiencies of treatment
modalities on response rates, post-treatment side effects, morbidity and mortality, and survival. MST with
SC using pemetrexed and cisplatin/gemcitabine ranged from 8.7% to 26.8%. However, no long-term
survivors were reported after SC alone.

In contrast, comprehensive treatment combined with CRS + POC showed significantly longer MST than SC
alone. In addition, CRS + POC demonstrated 10-year survivals of 12%-35%. Accordingly, CRS + POC is an
innovative treatment that can cure selected DMPM patients. Selection criteria include performance status
(ECOG PS ≤ 1), no extraperitoneal metastasis, PCI below cutoff levels, and histologic type (epithelioid type).
However, after CRS, postoperative morbidity and mortality rates were significantly higher than with the
more usual operations. Therefore, CRS and POC should be performed in specialized PSM centers.