The Role of Hyperthermic Intraperitoneal Chemotherapy for Non-colorectal Peritoneal Surface Malignancies

Our plain-English summary of The Role of Hyperthermic Intraperitoneal Chemotherapy for Non-colorectal Peritoneal Surface Malignancies, by M.C. Morris, J.M. Cloyd, J. Hays, et al (Journal of Gastrointestinal Surgery, 2021).

The study

• Authors: M.C. Morris, J.M. Cloyd, J. Hays, S.H. Patel
• Journal: Journal of Gastrointestinal Surgery
• Published: 2021;25(1):303-318
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Peritoneal carcinomatosis, from a variety of gastrointestinal and gynecological malignancies, has been historically challenging to treat and there remains a wide range of biologic aggressiveness in these patients. Malignancies commonly associated with PC include those of colorectal, appendiceal, gastric, ovarian, sarcoma, small intestinal, and primary peritoneal origin among others. Advances in our understanding of this unique disease process have led to significant interest in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as an emerging treatment option. The goal of CRS-HIPEC is to remove all visible macroscopic disease while preserving organ function, and then treat microscopic disease through perfusion of the peritoneal cavity with heated chemotherapy.

Purpose: Although recent reviews have focused on the management of peritoneal carcinomatosis secondary to colorectal cancer given the publication of several recent randomized controlled trials, the purpose of the current review is to summarize the evidence on CRS-HIPEC for non-colorectal peritoneal surface malignancies, including appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer, and ovarian cancer.

Results: While retrospective studies have clarified the importance of prognostic factors such as the peritoneal carcinomatosis index, completeness of cytoreduction, histopathological characteristics, and lymph node positivity, the lack of convincing level 1 evidence for the use of CRS-HIPEC has led to it remaining a highly controversial topic.

Conclusion: The decision to utilize CRS-HIPEC should involve a multidisciplinary team approach and evaluation of prognostic factors to balance the short-term morbidity of the operation with maximum long-term benefits. Large, multi-institutional groups and ongoing trials hold promise for clarifying the role of CRS-HIPEC in peritoneal surface malignancies.

In plain English

This was a review article. The authors summarized published evidence on cytoreductive surgery followed by heated chemotherapy inside the abdomen (CRS-HIPEC) for cancers spread across the abdominal lining other than colorectal cancer: appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer and ovarian cancer. As background, the review stated that previous asbestos exposure is linked to 80% of pleural mesothelioma cases but only 30–50% of peritoneal mesothelioma. The review did not study asbestos exposure itself. Among the mesothelioma studies it cited, an Australian multi-institutional study of 401 patients reported a median overall survival of 53 months. A US multi-center study of over 200 patients reported 38.4 months, with better survival when cisplatin rather than mitomycin-C was used. Major (grade III/IV) complications occurred in up to 40% of patients, and operative deaths were generally 1 to 2%. The authors noted a lack of convincing level 1 evidence. They concluded that in properly selected patients with resectable peritoneal mesothelioma, CRS-HIPEC can show a substantial survival benefit and is the recommended treatment, and that decisions should involve a multidisciplinary team.

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: Narrative review of published studies (no new patient data)
• Who was studied: Published studies of patients with non-colorectal peritoneal surface malignancies: appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer and ovarian cancer
• Exposure: The review is about a treatment, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), not about asbestos exposure. As background only, it states that previous asbestos exposure is linked to 80% of pleural mesothelioma cases but only 30–50% of malignant peritoneal mesothelioma (MPM).
• Main results:
  • A cited multi-institutional study from Australia of 401 patients treated with CRS-HIPEC for malignant peritoneal mesothelioma reported a median overall survival of 53 months, and 3- and 5-year overall survival of 60% and 47%.
  • A cited multi-center US study of over 200 patients with malignant peritoneal mesothelioma reported a median actuarial overall survival of 38.4 months. Survival was better with cisplatin than with mitomycin-C during HIPEC (for mitomycin-C, HR 2.58, 95% CI 1.49–4.47, p less than 0.01).
  • A cited study by Blackham et al. of patients with malignant peritoneal mesothelioma reported median overall survival of 10.8 months with mitomycin-C and 40.8 months with cisplatin. This difference had p = 0.22.
  • In malignant peritoneal mesothelioma, the sarcomatoid subtype was described as having a median overall survival of 5 months irrespective of treatment.
  • For CRS-HIPEC in malignant peritoneal mesothelioma, major postoperative morbidity (grade III/IV) was reported in up to 40% of patients, with operative mortality generally between 1 and 2%.
  • For ovarian cancer, the cited randomized trial by van Driel et al. (245 patients with stage III epithelial ovarian cancer) reported median overall survival of 33.9 months with CRS alone and 45.7 months with CRS-HIPEC.
  • For gastric cancer, the cited randomized phase 3 study by Yang et al. (68 patients) reported median overall survival of 11.0 months with CRS-HIPEC and 6.5 months with CRS alone (p less than 0.05).
• The authors' conclusion: The authors concluded that CRS-HIPEC has a role in malignant peritoneal mesothelioma, with the decision based on histology and disease burden. In properly selected patients it can show a substantial survival benefit and is the recommended treatment for resectable disease. Overall, decisions on CRS-HIPEC should involve a multidisciplinary team and evaluation of prognostic factors.
• Limitations the authors state:
  • The authors state that level I evidence for HIPEC is less established than for other treatments, because peritoneal carcinomatosis is rare, patients are heterogeneous, and large prospective trials are difficult to carry out.
  • The authors state that the lack of convincing level 1 evidence leaves CRS-HIPEC a controversial topic, and that the evidence comes largely from retrospective studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: HIPEC, Sarcoma, Cytoreductive Surgery, Peritoneal Cavity, Chemotherapy, Colorectal Cancer, Neoplasm, Peritoneal Mesothelioma.

Related studies

• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)
• Drugs, doses, and durations of intraperitoneal chemotherapy: standardising HIPEC and EPIC for colorectal, appendiceal, gastric, ovarian peritoneal surface malignancies and peritoneal mesothelioma — L. Lemoine, P. Sugarbaker, et al. (2017)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures — G. Passot, D. Vaudoyer, et al. (2016)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Asian patients: 100 consecutive patients in a single institution — M.C. Teo, G.H. Tan, et al. (2013)

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