Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC)

Abstract

Background: Prognosis of diffuse malignant peritoneal mesothelioma (DMPM) has been recently improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). As with other peritoneal surface malignancies, the survival benefit is maximal when a complete surgical cytoreduction is achieved, but additional factors predicting long-term outcome are still poorly understood. We sought to investigate outcome and prognostic factors in patients with DMPM treated by complete cytoreduction and HIPEC.

Methods: From a prospective database, we selected 108 patients with DMPM undergoing complete cytoreduction (residual tumour nodules ≤2.5 mm) and closed-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C. Twenty-seven patient-, tumour- and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. A panel of immunohistochemical markers was tested.

Results: Operative mortality was 1.9% and major morbidity 38.9%. Median follow-up was 48.8 months (95% confidence interval (CI) 37.1-60.6). Median OS and PFS were 63.2 months (95%CI 29.6-96.7) and 25.1 months (95%CI 5.1-45.1). The survival curve reached a plateau after 7 years, representing 19 actual survivors of 39 patients (43.6%) with potential follow-up ≥7 years. Cytokeratin 5/6, calretinin, Wilms tumour-1 (WT-1), podoplanin and epithelial growth factor receptor (EGFR) were mostly positive. At multivariate analysis, epithelial histological subtype, negative lymph-nodes, ≤10% Ki67-positive cells correlated with both increased OS and PFS. Positive podoplanin correlated to increased PFS.

Conclusions: After complete cytoreduction and HIPEC, prognosis of DMPM is primarily dependent on pathologic and biologic features. Patients with DMPM surviving ≥7 years appeared to be cured. Cure rate was 43.6%. Proliferative index and podoplanin may be used for prognostic stratification.

Keywords: Cytoreductive surgery; Diffuse malignant peritoneal mesothelioma; HIPEC; Hyperthermic intraperitoneal chemotherapy; Peritoneal surface malignancies; Peritonectomy.