Management of Patients with Malignant Peritoneal Mesothelioma: The Evolving Role of Surgery and Immunotherapy

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Yelizaveta V Gribkova Henry Richard Alexander


Malignant peritoneal mesothelioma, a neoplastic process that arises from the peritoneal membranes and presents as a diffuse malignant process, has an incidence of approximately 400-600 new cases annually in the United States. Systemic chemotherapy regimens, like the combination of cisplatin and pemetrexed, have response rates of approximately 25% in peritoneal mesothelioma. Due to chemotherapy’s poor response rates, the first line approach to treating malignant peritoneal mesothelioma over the last 30 years has been surgical resection with regional intra-peritoneal chemotherapy in appropriately selected patients. Hyperthermic intraoperative intraperitoneal perfusion with chemotherapy with cisplatin or mitomycin c for 90 to 120 minutes is the most commonly reported type of regional chemotherapy that is administered during surgical cytoreduction. Favorable prognostic factors for patient outcomes after cytoreduction and hyperthermic intraperitoneal perfusion with chemotherapy tend to be favorable operative characteristics (lower peritoneal cancer index, better complete cytoreduction score), less aggressive tumor characteristics (epithelioid histology, low Ki-67, well-differentiated), and other patient characteristics (young, female, fewer comorbidities). Recently, there has been considerable interest in the utility of immune checkpoint inhibitors either alone or in combination with chemotherapy for patients with mesothelioma. Data demonstrate that programmed death-ligand 1 may be highly expressed in a large proportion of malignant peritoneal mesothelioma tumors and therefore the evaluation of checkpoint blockade in this patient population is a high clinical priority.

Keywords: Malignant Peritoneal Mesothelioma, Peritoneal Mesothelioma, Management of Patients with Malignant Peritoneal Mesothelioma

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GRIBKOVA, Yelizaveta V; ALEXANDER, Henry Richard. Management of Patients with Malignant Peritoneal Mesothelioma: The Evolving Role of Surgery and Immunotherapy. Medical Research Archives, [S.l.], v. 10, n. 11, nov. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 17 june 2024. doi:
Review Articles


1. Carbone M, Adusumilli PS, Alexander HR, Jr., et al. Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69(5):402-429.
2. Testa JR, Cheung M, Pei J, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022-1025.
3. Miller J, Wynn, W.H.;. Malignant tumor arising from endothelium of peritoneum, and producing mucoid ascitic fluid. . JPath& Bact. 1908;12:267-278.
4. Winslow DJ, Taylor HB. Malignant peritoneal mesotheliomas: a clinicopathological analysis of 12 fatal cases. Cancer. 1960;13:127-136.
5. Selikoff IJ, Churg J, Hammond EC. RELATION BETWEEN EXPOSURE TO ASBESTOS AND MESOTHELIOMA. N Engl J Med. 1965;272:560-565.
6. Moertel CG. Peritoneal mesothelioma. Gastroenterology. 1972;63(2):346-350.
7. Antman KH. Current concepts: malignant mesothelioma. N Engl J Med. 1980;303(4):200-202.
8. Alexander HR, Hanna N, Pingpank JF. Clinical results of cytoreduction and HIPEC for malignant peritoneal mesothelioma. Cancer Treat Res. 2007;134:343-355.
9. Baratti D, Kusamura S, Sironi A, et al. Multicystic peritoneal mesothelioma treated by surgical cytoreduction and hyperthermic intra-peritoneal chemotherapy (HIPEC). In Vivo. 2008;22(1):153-157.
10. Husain AN, Colby TV, Ordonez NG, et al. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2017.
11. Offin M, Yang SR, Egger J, et al. Molecular Characterization of Peritoneal Mesotheliomas. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2021.
12. Jänne PA, Wozniak AJ, Belani CP, et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer. 2005;7(1):40-46.
13. Simon GR, Verschraegen CF, Jänne PA, et al. Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial. J Clin Oncol. 2008;26(21):3567-3572.
14. Miura JT, Johnston FM, Gamblin TC, Turaga KK. Current trends in the management of malignant peritoneal mesothelioma. Ann Surg Oncol. 2014;21(12):3947-3953.
15. Ullah A, Waheed A, Khan J, et al. Incidence, Survival Analysis and Future Perspective of Primary Peritoneal Mesothelioma (PPM): A Population-Based Study from SEER Database. Cancers (Basel). 2022;14(4).
16. Pan D, Wang M, Liu W, Li Y, Sang L, Chang B. Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly. BMC Gastroenterol. 2022;22(1):292.
17. Bijelic L, Darcy K, Stodghill J, Tian C, Cannon T. Predictors and Outcomes of Surgery in Peritoneal Mesothelioma: an Analysis of 2000 Patients from the National Cancer Database. Ann Surg Oncol. 2020;27(8):2974-2982.
18. Verma V, Sleightholm RL, Rusthoven CG, et al. Malignant Peritoneal Mesothelioma: National Practice Patterns, Outcomes, and Predictors of Survival. Ann Surg Oncol. 2018;25(7):2018-2026.
19. Naffouje SA, Tulla KA, Salti GI. The impact of chemotherapy and its timing on survival in malignant peritoneal mesothelioma treated with complete debulking. Med Oncol. 2018;35(5):69.
20. Shavelle R, Vavra-Musser K, Lee J, Brooks J. Life Expectancy in Pleural and Peritoneal Mesothelioma. Lung Cancer Int. 2017;2017:2782590.
21. Roife D, Powers BD, Zaidi MY, et al. CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative. Ann Surg Oncol. 2020;27(13):4996-5004.
22. Malgras B, Gayat E, Aoun O, et al. Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study. Ann Surg Oncol. 2018;25(11):3271-3279.
23. Kepenekian V, Elias D, Passot G, et al. Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study. Eur J Cancer. 2016;65:69-79.
24. Deraco M, Nizri E, Glehen O, et al. Well differentiated papillary peritoneal mesothelioma treated by cytoreduction and hyperthermic intraperitoneal chemotherapy-the experience of the PSOGI registry. Eur J Surg Oncol. 2019;45(3):371-375.
25. Sugarbaker PH, Chang D. Long-term regional chemotherapy for patients with epithelial malignant peritoneal mesothelioma results in improved survival. Eur J Surg Oncol. 2017;43(7):1228-1235.
26. Li YC, Khashab T, Terhune J, et al. Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2017;24(8):2259-2265.
27. Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(4):1093-1100.
28. Schaub NP, Alimchandani M, Quezado M, et al. A novel nomogram for peritoneal mesothelioma predicts survival. Ann Surg Oncol. 2013;20(2):555-561.
29. Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer. 2013;49(15):3140-3148.
30. Alexander HR, Jr., Bartlett DL, Pingpank JF, et al. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery. 2013;153(6):779-786.
31. Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237-6242.
32. Kyziridis D, Hristakis C, Kalakonas A, et al. Ten-year experience with peritoneal mesothelioma. J buon. 2019;24(1):391-396.
33. Chapel DB, Schulte JJ, Absenger G, et al. Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases. Mod Pathol. 2021;34(2):380-395.
34. Hassan R, Thomas A, Nemunaitis JJ, et al. Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA oncology. 2019;5(3):351-357.
35. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386.
36. Hotta K, Fujimoto N, Kozuki T, Aoe K, Kiura K. Nivolumab for the treatment of unresectable pleural mesothelioma. Expert Opin Biol Ther. 2020;20(2):109-114.
37. Calabrò L, Rossi G, Morra A, et al. Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study. Lancet Respir Med. 2021;9(9):969-976.
38. Fennell DA, Ewings S, Ottensmeier C, et al. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2021;22(11):1530-1540.
39. Chapel DB, Stewart R, Furtado LV, Husain AN, Krausz T, Deftereos G. Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays. Hum Pathol. 2019;87:11-17.
40. Raghav K, Liu S, Overman M, et al. Clinical Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Malignant Peritoneal Mesothelioma. JAMA Netw Open. 2021;4(8):e2119934.
41. Gazivoda VP, Kangas-Dick AW, Greenbaum AA, et al. Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study. J Surg Res. 2022;277:131-137.
42. 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(3):564-566.
43. Raghav K, Liu S, Overman MJ, et al. Efficacy, Safety, and Biomarker Analysis of Combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal Mesothelioma. Cancer discovery. 2021;11(11):2738-2747.
44. The University of Chicago C, Illinois, United States. A Study of Immunotherapy Drugs Nivolumab and Ipilimumab in Patients w/Resectable Malignant Peritoneal Mesothelioma. https://ClinicalTrialsgov/show/NCT05041062. 2022.
45. Erasmus Medical Center R, Zuid-Holland, Netherlands. Intraperitoneal Paclitaxel for Patients With Primary Malignant Peritoneal Mesothelioma. In.
46. Institut réginal du Cancer de Montpellier M, France. Treatment of Malignant Peritoneal Mesothelioma (MESOTIP). https://ClinicalTrialsgov/show/NCT03875144. 2022.
47. de Boer NL, van Kooten JP, Burger JWA, Verhoef C, Aerts J, Madsen EVE. Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial. BMJ Open. 2019;9(5):e026779.
48. Trempolec N, Doix B, Degavre C, et al. Photodynamic Therapy-Based Dendritic Cell Vaccination Suited to Treat Peritoneal Mesothelioma. Cancers (Basel). 2020;12(3).