Cytoreductive Surgery With or Without HITHOC for Pleural Mesothelioma: A Meta-analysis of Survival and Perioperative Outcomes.

BACKGROUND

Pleural mesothelioma (PM) is a rare and aggressive malignancy with limited overall survival (OS) despite multimodal therapy. Cytoreductive surgery is the standard of care for selected patients. However, locoregional recurrence remains common. Hyperthermic intrathoracic chemotherapy (HITHOC) has been proposed as an adjunct to enhance local disease control.

METHODS

A systematic review and meta-analysis were performed according to PRISMA guidelines and registered in PROSPERO (CRD420251132268). This study searched PubMed, Embase, and Cochrane Library up to 18 July 2025. Pooled hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) were calculated using random-effects models. Individual patient data (IPD) were reconstructed to generate Kaplan-Meier curves.

RESULTS

Six studies comprising 1060 patients were included. Of these patients, 490 (46.2%) received HITHOC and 570 (53.8%) underwent surgery without HITHOC. Overall survival analysis showed a significant survival benefit for HITHOC (HR, 0.82; 95% confidence interval [CI] 0.71-0.94). The median OS was 21.3 months (95% CI, 19.2-24.9 months) in the HITHOC group versus 18.8 months (95% CI, 17.5-20.9 months) in the non-HITHOC group. No statistically significant differences were found for 30-day mortality (OR, 0.53; 95% CI, 0.16-1.05), 90-day mortality (OR, 0.49; 95% CI, 0.24-1.01), bronchopleural fistula/empyema (OR, 0.55; 95% CI, 0.07-4.12), arrhythmia (OR, 1.17; 95% CI, 0.45-3.06), or hospital length of stay (MD, 0.38 days; 95% CI, -4.61 to 5.37 days).

CONCLUSION

For patients undergoing cytoreductive surgery for pleural mesothelioma, HITHOC is associated with a significant improvement in OS without increased early postoperative risk. These findings support the use of HITHOC in specialized centers with appropriate surgical expertise and patient selection.