Systemic Therapy Use and Outcomes After Relapse from Preoperative Radiation and Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma.

Background: Multimodality therapy with preoperative radiation (RT) followed by extrapleural pneumonectomy (EP) for patients with operable malignant pleural mesothelioma (MPM) has demonstrated encouraging results. At relapse, there are few data on the tolerance and efficacy of systemic therapies after prior multimodality therapy.

Materials And Methods: We conducted a retrospective analysis of patients with relapsed MPM after RT and EPP ± adjuvant chemotherapy to determine overall survival (OS; date of relapse to death) and the proportion of patients that received systemic therapy and associated response rate (RR). OS was estimated using Kaplan-Meier method and potential prognostic variables were examined.

Results: Fifty-three patients were included (2008-2016). Median OS was 4.8 months (median follow-up 4.4 months, range 0.03-34.8). Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, disease-free interval (DFI) <1 year, and hemoglobin ≤110 g/L at recurrence were associated with worse prognosis. Thirty-six percent of patients received any systemic therapy, whereas it was omitted in 62% because of poor PS. RR was 15% (0 complete responses, 15% partial responses) in 13 individuals with response-evaluable disease. Therapy was discontinued because of toxicity (6/15) or disease progression (5/15), and median number of cycles was four.

Conclusion: Patients with relapsed MPM following RT and EPP, especially those with ECOG PS ≥2, DFI <1 year, and hemoglobin ≤110 g/L at recurrence, have poor prognosis and low RR to first-line systemic therapy. Earlier detection and novel diagnostic markers of relapse as well as potential neoadjuvant or adjuvant systemic therapy should be investigated in future studies.

Implications For Practice: The results of this study have reinforced the importance of careful selection of appropriate candidates for this combined-modality approach and favor prompt detection of recurrence with early and regular postoperative imaging and biopsy of suspected relapsed disease along with rapid initiation of systemic therapy even in patients with very low burden of disease. Furthermore, with the emergence of new systemic agents targeting different histological subtypes of malignant pleural mesothelioma, histological sampling of recurrence could inform therapeutic decisions in the future.