Surgery and Adjuvant or Neoadjuvant Setting of Radiotherapy: What Is the Role of Radiotherapy in Combination with Lung-Sparing Surgery?

Malignant pleural mesothelioma (MPM) is a locally aggressive disease. Whereas curative-intent surgery, non-lung-sparing surgery (extrapleural pneumonectomy [EPP]), or lung-sparing surgery (pleurectomy/decortication [P/D]), may achieve a macroscopic complete resection (MCR), surgery alone is generally insufficient for local disease control. Adjuvant or neoadjuvant radiotherapy (RT) in combination with surgery potentially reduces locoregional recurrence rate, although no definitive evidence showing a robust survival benefit with its use has been reported. Adjuvant hemithoracic RT after non-lung-sparing surgery (EPP) may be offered to selected patients with good performance status. In the neoadjuvant setting before EPP, the delivery of high-dose RT to the entire hemithorax with two intact lungs without significant lung toxicities is technically challenging. However, modern RT techniques such as intensity-modulated RT (IMRT) have enabled neoadjuvant RT following EPP. Lung-sparing surgery has been increasingly employed, as is associated with lower operative morbidity and mortality. Adjuvant hemithoracic IMRT can be performed with acceptable toxicities and may provide a favorable survival in patients who received lung-sparing surgery. Despite these promising results, either neoadjuvant IMRT before EPP or adjuvant IMRT after P/D remains experimental due to its potential risk of fetal lung toxicities, and should only be performed in highly experienced centers, preferably in the context of a clinical trial. Here, we reviewed the current status and future perspectives of adjuvant or neoadjuvant RT in combination with surgery for MPM.