National Guidelines for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Malignancies: A Worldwide Systematic Review and Recommendations of Strength Analysis

Our plain-English summary of National Guidelines for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Malignancies: A Worldwide Systematic Review and Recommendations of Strength Analysis, by M. Tonello, C. Cenzi, E. Pizzolato, et al (Annals of Surgical Oncology, 2025).

The study

• Authors: M. Tonello, C. Cenzi, E. Pizzolato, M. Martini, P. Pilati, A. Sommariva
• Journal: Annals of Surgical Oncology
• Published: 2025;32(8):5795-5806
• Type of article: Systematic review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: National guidelines (GLs) for surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of peritoneal malignancies (PMs) vary across countries, scientific societies, and government agencies. This study aimed to systematically review and compare the recommendations for CRS/HIPEC in the treatment of ovarian cancer (EOC), gastric cancer, colorectal cancer (CRC), mesothelioma, and pseudomyxoma peritonei (PMP).

Methods: Medical databases, search engines, and national websites of 193 countries were queried using artificial intelligence (AI)-powered software for scientific societies and/or government agencies guidelines. The study excluded consensus statements and guidelines without appropriate references. Non-English guidelines were translated, and data, including GRADE strength of recommendations, were extracted.

Results: The study analyzed 138 guidelines, 24 for gastric cancer, 36 for colorectal cancer, 29 for primary ovarian cancer (p-)EOC, 28 for recurrent ovarian cancer (r-)EOC, 10 for mesothelioma, and 11 for PMP. Guidelines were retrieved from 51 (26.4%) nations, mostly from developed countries (62.1%; p < 0.001). The CRS procedure received robust positive recommendations (GRADE I/IIa) for CRC (74.2%), p-/r-EOC (100%/78.5%), PMP (90.9%), and mesothelioma (90.0%). Conversely, CRS was not indicated for gastric cancer (61.6%, GRADE III; p < 0.001). The HIPEC procedure had robust positive recommendations for PMP (90.9%) and mesothelioma (90.0%), but was controversial for p-EOC (42.3%) and CRC (38.0%) and contraindicated for r-EOC (80.0%) and gastric cancer (62.4%) (p < 0.001).

Conclusion: National guidelines concordantly recommend CRS for colorectal cancer, ovarian cancer, PMP, and mesothelioma. In contrast, HIPEC recommendations are less homogeneously shared, except for PMP and mesothelioma. No positive concordance exists among guidelines on gastric cancer for CRS nor HIPEC. Furthermore, high-level evidence is needed to strengthen future guidelines on peritoneal metastases.

© 2025. The Author(s).

In plain English

This article systematically reviewed treatment guidelines; it did not study patients. In December 2024 the authors searched databases, search engines and websites for the 193 United Nations member countries, partly using AI tools. They analyzed 138 guidelines, from 51 countries or international societies, on cytoreductive surgery (CRS), which removes visible tumor, and heated chemotherapy given into the abdomen (HIPEC). For malignant peritoneal mesothelioma (epithelial subtype), 9 of 10 guidelines (90.0%) gave positive recommendations for both CRS and HIPEC. For pseudomyxoma peritonei, 10 of 11 (90.9%) did. CRS was widely recommended for peritoneal metastases from colorectal and high-grade serous ovarian cancer, with selection criteria such as platinum sensitivity for recurrent ovarian cancer. HIPEC advice was divided for colorectal and primary ovarian disease. Only 10 of 28 recurrent ovarian guidelines mentioned HIPEC, and 8 of those advised against it. Most gastric cancer guidelines addressing these treatments advised against them. The authors concluded that HIPEC is clearly and consistently recommended only for pseudomyxoma peritonei and mesothelioma, and that more high-level evidence is needed. They noted that some guidelines may have been missed or misread. Asbestos is not discussed.

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: Systematic review of national and international clinical guidelines. The authors also call it a scoping review, and it was not registered with PROSPERO.
• Who was studied: 138 guidelines on CRS and/or HIPEC for peritoneal malignancies, from 51 countries or international societies. The search covered the 193 UN member countries and was run between 1 and 20 December 2024. The guidelines covered six groups of peritoneal disease: 24 for metastases from gastric cancer, 36 for metastases from colorectal cancer, 29 for primary and 28 for recurrent high-grade serous ovarian cancer, 10 for malignant peritoneal mesothelioma (epithelial subtype) and 11 for pseudomyxoma peritonei.
• Exposure: This was not an exposure study. It looked at what guidelines recommend about two treatments: cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Asbestos and fiber types are not discussed.
• Main results:
  • Malignant peritoneal mesothelioma: 10 guidelines were found. All but one considered CRS and HIPEC standard treatment, so 9 of 10 (90.0%) were positive for each.
  • For HIPEC, the guidelines largely agreed for mesothelioma (90.0% positive) and for pseudomyxoma peritonei (90.9% positive), each with p less than 0.001.
  • Pseudomyxoma peritonei: 11 guidelines were found. 10 (90.9%) gave positive recommendations for CRS and for HIPEC.
  • Peritoneal metastases from gastric cancer (24 guidelines): 18 mentioned CRS, and 11 of these (61.1%) recommended against it. 16 cited HIPEC, and 10 of these (62.5%) recommended against it.
  • Peritoneal metastases from colorectal cancer (36 guidelines): 31 cited CRS, and 30 of these (96.8%) gave positive indications. 29 discussed HIPEC, and 18 of these (62.1%) recommended it.
  • Peritoneal metastases from high-grade serous ovarian cancer and CRS: CRS received a strong or moderate (GRADE I/IIa) endorsement in 100% of primary-setting guidelines and in 78.4% of recurrent-setting guidelines. For recurrent patients, the guidelines set specific selection criteria such as platinum sensitivity.
  • Primary ovarian cancer and HIPEC: HIPEC was cited in 26 of 29 guidelines. It was recommended in 15 of these (57.7%) and recommended against in 10 (38.5%).
  • Recurrent ovarian cancer and HIPEC: HIPEC was cited in only 10 of 28 guidelines (35.7%). 8 of these 10 (80.0%) recommended against it.
  • Countries: 23 developed countries (62.2%) had published or endorsed at least one guideline. The figures for other groups were 25.0% of developing countries and none of the least-developed countries (p less than 0.001).
  • How strongly the guidelines agreed differed significantly between tumor types, for both CRS and HIPEC (p less than 0.001 for each).
• The authors' conclusion: The authors concluded that recommendations for CRS are positive and consistent for colorectal cancer, epithelial ovarian carcinoma, pseudomyxoma peritonei and peritoneal mesothelioma. In their view, HIPEC is clearly and consistently recommended only for pseudomyxoma peritonei and mesothelioma, while CRS and HIPEC are debated for gastric cancer. They added that more high-level evidence is needed.
• Limitations the authors state:
  • The search engines and AI tools use proprietary algorithms that may have biased which records were found, so some published guidelines may have been overlooked.
  • Most guidelines came from developed countries, which may bias the results. The authors tried to reduce this by searching manually.
  • Where a guideline did not state a GRADE strength, the authors converted its wording into one. They said this conversion, and the interpretation of the wording, could introduce errors.
  • Translation by non-English-speaking authors and by AI translation tools may have introduced errors.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Systematic Review, Ovarian Cancer, Stomach Cancer, Colorectal Cancer, Mesothelioma.

Related studies

• The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan — T. Kitai (2021)
• Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry — A. Arjona-Sanchez, O. Aziz, et al. (2021)
• Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review — D. Chen, Y. Ma, et al. (2025)
• Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — M. Alyami, F. Mercier, et al. (2021)
• Prognostic importance of the neutrophil-to-lymphocyte ratio in malignant peritoneal mesothelioma patients receiving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — Z. Xinjing, G. Lei, et al. (2025)
• The Safety of Iterative Cytoreductive Surgery and HIPEC for Peritoneal Carcinomatosis: A High Volume Center Prospectively Maintained Database Analysis — E. Bekhor, J. Carr, et al. (2020)

Browse more research in Annals of Surgical Oncology, or return to medical research.