Towards a new approach in pleural mesothelioma: Perioperative immunotherapy and its implications

Pleural mesothelioma is a rare malignancy that has historically had a poor prognosis, even with systemic chemotherapy. Although immune checkpoint inhibitors have improved survival rates for patients with advanced, unresectable disease, their role in perioperative management is unclear. We conducted a review of early-phase trials and case series examining the use of immune checkpoint blockade alone or in combination with platinum-based chemotherapy and surgery for pleural mesothelioma. We then contrasted these findings with established perioperative immunotherapy paradigms in non-small cell lung cancer. For pleural mesothelioma, feasibility studies have reported a major pathological response in up to 25 % of patients, a median progression-free survival of 14-19 months and sporadic instances of a pathological complete response. These studies have also reported acceptable toxicity and surgical timings. In contrast, non-small cell lung cancer trials have demonstrated consistent major pathological response rates of over 50 %, significant event-free survival benefits and validated complete response endpoints. These divergent outcomes reflect differences in tumor microenvironment, mutational burden, histological subtypes and predictive biomarkers between the two diseases. Our analysis highlights the need for standardized pathological endpoints, refined patient selection criteria and larger randomized studies to optimize the sequencing and combination of immunotherapy, chemotherapy and surgery in pleural mesothelioma. Such efforts are essential for integrating perioperative immune strategies into multimodal care and improving long-term outcomes.