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

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.

Keywords: Cytoreductive surgery (CRS); HIPEC; National guidelines; Peritoneal malignancies.

Fig. 1

PRISMA flowchart of literature search. Note: records included also guidelines with multiple tumor types (e.g., GL on peritoneal malignancies were counted as five items because they addressed gastric, colorectal, primary, and recurrent ovarian cancer PM). PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; GL, national guidelines; PM, peritoneal malignancy

Fig. 2

Countries with national guidelines

Fig. 3

Recommended GRADE in guidelines. GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; GC, gastric cancer; CRC, colorectal cancer; p-EOC, primary epithelial ovarian cancer; r-EOC, recurrent epithelial ovarian cancer; MM, malignant mesothelioma (epithelial); PMP, pseudomyxoma peritonei; CRS, cytoreductive surgery; HIPEC, intraperitoneal hyperthermic chemotherapy.