Impact of histological subtype on outcomes of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: A systematic review and meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) has transformed survival in peritoneal mesothelioma (PeM), but is still often withheld from non-epithelioid patients on histological grounds. OBJECTIVE: To quantify the prognostic impact of non-epithelioid histology on overall survival after CRS ± HIPEC in PeM. METHODS: We searched PubMed/MEDLINE, Embase and Cochrane CENTRAL to 7 April 2026 for studies reporting survival after CRS ± HIPEC in PeM by histological subtype. Screening and extraction were duplicated. The primary analysis pooled multivariable-adjusted hazard ratios (HRs) from the institution-unique surgical cohorts; adding the two population registries was secondary (PROSPERO: CRD420261360349). RESULTS: Twenty-two studies (7017 patients) were included; six reported a multivariable-adjusted HR on an institution-unique series, four surgical. In the primary analysis, non-epithelioid histology was associated with worse overall survival (HR 3.38; 95% CI 1.22-9.35; p = 0.032; I2 = 50.3%), but the estimate is fragile: every leave-one-out iteration crossed unity (2.63 to 4.24), the prediction interval ran 0.33-34.23, and only 39 non-epithelioid patients contribute. Adding the two population registries gave 2.30 (1.21-4.37). Publication bias was not assessable at k = 4; trim-and-fill gave 2.71 (0.98-7.53). Reported whole-cohort five-year survival ranged from 39% to 52.4%, not pooled. GRADE certainty was very low. CONCLUSIONS: Non-epithelioid histology is associated with worse overall survival after CRS ± HIPEC in every analysis performed. The direction is consistent; the magnitude is not, resting on very few patients and not surviving removal of any single study. Histological subtype should inform selection for surgery rather than decide it.