Post-Recurrence Treatment Patterns and Outcomes After Curative-Intent Multimodality Strategy in Patients with Pleural Mesothelioma: A Retrospective Cohort Study

Background: Disease recurrence is common after surgery for pleural mesothelioma (PM), and the evidence guiding post-recurrence management remains limited. Methods: We conducted a retrospective, single-center cohort study including patients with PM treated within a curative-intent multimodality treatment pathway including surgery aiming for a macroscopic complete resection when feasible between 2001 and 2024. Post-recurrence treatments were categorized as best supportive care only (BSC), systemic therapy alone, or local with or without systemic therapy. Survival and disease-free outcomes were analyzed in relation to treatment patterns and clinical prognostic factors. Results: Among 67 patients with a median follow-up time of 107 months from surgery, 58 (86.6%) developed disease recurrence. At first recurrence, 21 patients (36%) received local with or without systemic therapy, 26 (45%) systemic therapy alone, and 11 (19%) BSC. The median post-recurrence survival was 21.7 months for patients receiving local with or without systemic therapy, 10.8 months for systemic therapy alone, and 1.6 months for BSC. Lung-sparing surgery and a disease-free interval of at least 12 months were associated with improved post-recurrence survival and post-recurrence progression-free survival. Conclusions: In this real-world cohort of patients with PM and extended follow-up, active post-recurrence treatment was associated with longer post-recurrence survival in selected patients. However, conclusions regarding their comparative effectiveness are limited by the retrospective design, incomplete recurrence-related data, and patient selection at recurrence.