Prognostic Factors in Patients with Peritoneal Mesothelioma Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Systematic Review and Meta-Analysis

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Abstract Background Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and aggressive disease in which cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival. However, recurrence rates remain high, highlighting the need for reliable prognostic factors to guide patient selection. This systematic review and meta-analysis aimed to evaluate prognostic factors in patients with DMPM undergoing CRS and HIPEC. Materials and Methods A systematic literature search of PubMed, MEDLINE, Cochrane Library, Embase, Scopus, and Web of Science was performed up to July 2024. Studies reporting prognostic factors associated with overall and/or progression-free survival were included. Data were pooled using random effects models. Heterogeneity was assessed using the I 2 statistic and Cochran’s Q test. Evaluation of publication bias and sensitivity analyses were conducted. Results A total of eleven studies comprising 891 patients were included. Incomplete cytoreduction, elevated peritoneal cancer index, grade 3–5 postoperative morbidity, prior chemotherapy exposure, World Health Organization performance status ≥ 1, biphasic or sarcomatoid histology, and elevated Ki-67 proliferation index were consistently associated with poorer survival outcomes. Evidence for additional prognostic factors was limited. No prognostic molecular biomarkers could be identified. Conclusions Established clinical–pathological, histological, and immunohistochemical parameters remain the most relevant prognostic factors in patients with DMPM undergoing CRS and HIPEC. These findings facilitate more refined patient selection and support the ongoing standardization of HIPEC protocols for this uncommon and aggressive malignancy. However, the current evidence base is limited and should be interpreted with caution. Future research should prioritize the integration of molecular and genetic biomarkers to enhance prognostic stratification and support personalized treatment approaches.