# The Role of Prognostic Clinical-Pathological, (Immuno-) Histological, and Molecular Parameters in Pseudomyxoma Peritonei Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Systematic Review and Meta-Analysis

## TL;DR

This study reviews factors affecting survival in pseudomyxoma peritonei patients treated with surgery and heated chemotherapy, emphasizing the need for personalized treatment based on patient and tumor characteristics.

## Contribution

A systematic review and meta-analysis identifying key prognostic factors for pseudomyxoma peritonei patients undergoing CRS and HIPEC.

## Key findings

- Age, sex, completeness of cytoreduction, and peritoneal cancer index are significantly associated with prognosis.
- Tumor markers like CEA, CA 19-9, and CA-125, along with tumor grade and Ki-67, are linked to patient outcomes.
- Heterogeneity and publication bias were observed, but clinical-pathological and histological parameters remain important for prognosis.

## Abstract

Pseudomyxoma peritonei is a rare condition in which mucinous tumor cells spread throughout the abdomen, most often originating from a ruptured mucinous tumor of the appendix. The principal therapeutic approach, combining cytoreductive surgery to remove visible disease with hyperthermic intraperitoneal chemotherapy, has greatly improved patient survival. However, recurrence remains a major concern, making careful selection of patients essential. This meta-analysis synthesizes the role of prognostic clinical-pathological, (immuno-) histological, and molecular parameters in pseudomyxoma peritonei patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The findings emphasize the importance of using detailed tumor and patient characteristics to guide personalized, multidisciplinary treatment decisions. Looking ahead, future research should integrate molecular and genetic biomarkers to further improve patient selection and optimize treatment results for pseudomyxoma peritonei patients.

Background/Objectives: While cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improve the outcome of pseudomyxoma peritonei (PMP) patients, recurrence remains a concern, highlighting the need for careful patient selection. This systematic review and meta-analysis evaluated the clinical-pathological, (immuno-) histological, and molecular prognostic factors in PMP patients undergoing CRS and HIPEC. Methods: Databases including PubMed, MEDLINE, Cochrane library, Embase, Scopus, and Web of Science were searched up to July 2024. Studies assessing clinical-pathological, (immuno-) histological, and molecular parameters influencing overall, progression-free, and/or disease-free survival were included. Statistical analysis was performed using R (Version 4.4.3) with random-effect models employed to address heterogeneity. Subsequent subgroup analyses were conducted to investigate potential sources of publication bias (Egger test). Results: A total of 16 studies involving 4009 PMP patients were included. Age, sex (male), completeness of cytoreduction score, peritoneal cancer index, tumor markers (CEA, CA 19-9, CA-125), tumor grade (high), histological subtype, and Ki-67 were significantly associated with prognosis prediction. Conclusions: Despite the presence of heterogeneity and publication bias, clinical-pathological and (immuno-) histological parameters were significantly associated with prognosis in PMP. The findings highlight the importance of integrating clinical-pathological and (immuno-) histological parameters in the individualized multidisciplinary management of PMP patients undergoing CRS and HIPEC. Future research should focus on incorporating molecular and genetic biomarkers to further refine patient selection and improve treatment outcomes.