Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma

Our plain-English summary of Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma, by H.R. Alexander, D.L. Bartlett, J.F. Pingpank, et al (Surgery, 2013).

The study

• Authors: H.R. Alexander, D.L. Bartlett, J.F. Pingpank, S.K. Libutti, R. Royal, M.S. Hughes, M. Holtzman, N. Hanna, K. Turner, T. Beresneva, Y. Zhu
• Journal: Surgery
• Published: 2013;153(6):779-86
• Cited by: 107 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome.

Methods: Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed.

Results: The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were younger age <60 years (P < .01), complete or near complete (R0-1) versus incomplete (R2-3) resection (P < .02), low versus high histologic grade (P < .01), and the use of cisplatin versus mitomycin-C during HIPEC (P < .01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89-2.41; P = .13).

Conclusion: Operative CRS with HIPEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM.

Copyright © 2013 Mosby, Inc. All rights reserved.

In plain English

This study looked back at 211 patients with malignant peritoneal mesothelioma, a cancer of the abdominal lining, treated at three U.S. centers between 1992 and 2011. All had surgery to remove visible tumor plus heated chemotherapy circulated through the abdomen during the operation (HIPEC), with cisplatin (105 patients) or mitomycin-C (106). Asbestos exposure was not studied. Median overall survival was 38.4 months. Estimated survival was 41% at 5 years and 26% at 10 years. In the combined analysis, shorter survival was linked to age over 60 (hazard ratio 2.05, 95% confidence interval 1.24 to 3.39), high-grade tumors (2.14, 1.17 to 3.91), incomplete tumor removal (1.81, 1.11 to 2.95) and mitomycin-C instead of cisplatin (2.58, 1.49 to 4.47). The higher hazard for men (1.46, 0.89 to 2.41) was not statistically significant. The cisplatin advantage was seen only in patients whose tumor was completely or nearly completely removed. The authors concluded that this treatment is associated with long-term survival in selected patients. They also concluded that their data do not support HIPEC when removal was suboptimal, meaning less than complete or near-complete, or when extensive visible tumor remained.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of treatment outcomes at 3 referral centers (Kaplan-Meier survival analysis and Cox multivariate analysis)
• Who was studied: 211 patients with malignant peritoneal mesothelioma treated 1992 to 2011 at the National Cancer Institute (97), University of Pittsburgh (72) and University of Maryland (42). 129 (61.1%) were female and 82 (38.9%) male. Median age was 52 years, range 15.6 to 84.6.
• Exposure: No asbestos or other environmental exposure was studied. The exposure compared was treatment: cytoreductive surgery followed by 90 minutes of HIPEC with cisplatin (median dose 250 mg/m2, 105 patients) or mitomycin-C (40 mg, 106 patients). Thirty-five National Cancer Institute patients also received intraperitoneal paclitaxel and 5-fluorouracil after surgery.
• Main results:
  • All 211 patients: median actuarial overall survival 38.4 months. Actuarial 5-year survival 41% and 10-year survival 26%.
  • Multivariate analysis, age over 60 vs under 60: hazard ratio 2.05 (95% CI 1.24 to 3.39), P less than .01
  • Multivariate analysis, high vs low histologic grade: hazard ratio 2.14 (95% CI 1.17 to 3.91), P = .01. Low grade was adenomatoid and tubulopapillary tumors; high grade was solid epithelioid and sarcomatoid tumors.
  • Multivariate analysis, incomplete (R2+R3) vs complete or near complete (R0+R1) tumor removal: hazard ratio 1.81 (95% CI 1.11 to 2.95), P = .02
  • Multivariate analysis, mitomycin-C vs cisplatin: hazard ratio 2.58 (95% CI 1.49 to 4.47), P less than .01
  • Multivariate analysis, male vs female sex: hazard ratio 1.46 (95% CI 0.89 to 2.41), P = .13, described as a trend. In the univariate analysis the male hazard ratio was 1.64 (1.08 to 2.49), P = .02.
  • The survival benefit of cisplatin over mitomycin-C was seen only in patients with optimal cytoreduction. In patients with suboptimal cytoreduction, outcome was poor whichever drug was used.
  • Complications: 63 of 211 patients (30%) had complications, 20 of 211 (9.4%) had an unplanned return to the operating room, operative mortality was 5 of 211 (2.3%), and median hospital stay was 11 days.
• The authors' conclusion: The authors concluded that surgery plus HIPEC is associated with long-term survival in selected patients with malignant peritoneal mesothelioma. They also stated that their data do not support HIPEC in patients with suboptimal cytoreduction (less than complete or near-complete removal) or extensive gross residual disease.
• Limitations the authors state:
  • Types of complications could be reported for only 135 patients at 2 sites, because 1 institution recorded only the severity of complications.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, Chemotherapy, Peritoneal Mesothelioma, Mesothelial Cells, Peritoneum, HIPEC, Overall Survival, Multivariate Analysis.

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• Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases — L.S. Kyang, N.A. Alzahrani, et al. (2019)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia — N. Alzahrani, J.S. Ferguson, et al. (2016)
• Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy — K.I. Votanopoulos, C. Ihemelandu, et al. (2012)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)

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