Perioperative Treatments in Pleural Mesothelioma: State of the Art and Future Directions

Our plain-English summary of Perioperative Treatments in Pleural Mesothelioma: State of the Art and Future Directions, by L.G. Cecchi, M. Aliprandi, F. De Vincenzo, et al (Cancers, 2025).

The study

• Authors: L.G. Cecchi, M. Aliprandi, F. De Vincenzo, M. Perrino, N. Cordua, F. Borea, A. Bertocchi, A. Federico, G. Marulli, A. Santoro, G.L. Ceresoli, P.A. Zucali
• Journal: Cancers
• Published: 2025;17(19)
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis. This review aims to consolidate recent findings on the efficacy of perioperative therapies encompassing chemotherapy, surgery, and emerging immunotherapy strategies. Current management strategies debate the role of surgery in early-stage patients, particularly due to the limited success of solitary treatment modalities and significant rates of postoperative complications. Retrospective studies indicate that multimodal treatment, incorporating surgical resection with perioperative chemotherapy, can enhance overall survival (OS), especially in favorable prognostic subsets. However, significant randomized trials, notably the MARS and MARS 2 trials, revealed that the addition of aggressive surgical strategies like extrapleural pneumonectomy (EPP) did not confer survival benefits and was accompanied by heightened morbidity. In light of persistent challenges, integrating perioperative chemotherapy-primarily with platinum-based regimens-has shown improved disease control outcomes. Neoadjuvant chemotherapy permits real-time assessment of tumor responsiveness, providing valuable clinical insights for surgical candidacy. The role of immunotherapy, particularly immune checkpoint inhibitors (ICIs), is also under active exploration, with preliminary results suggesting promising activity and manageable safety profiles. In conclusion, while current protocols primarily recommend surgery for a select group of patients, ongoing investigations into neoadjuvant approaches, adjuvant therapies, and novel immunotherapeutic strategies are crucial for developing effective, personalized treatment paradigms for PM. Future efforts should prioritize clinical trials that integrate these therapies within a structured multidisciplinary approach to optimize patient outcomes.

In plain English

This article was a review, not a new study. The authors searched PubMed for research on treatments given around the time of surgery for pleural mesothelioma, a cancer they described as primarily associated with asbestos exposure. Asbestos exposure itself was not studied. The review covered radiotherapy, chemotherapy, heated chemotherapy during surgery, and immunotherapy. In the MARS and MARS 2 trials, adding surgery to chemotherapy may have been detrimental compared with chemotherapy alone. Deaths within 90 days of the operation were 8.9% in MARS 2 versus 1.7% in the EORTC 1205 trial, a comparison the authors cautioned may introduce bias. One randomized trial enrolled patients with visible tumor left after non-radical lung-sparing surgery. In that trial, two-year survival was 58% with radical radiotherapy versus 28% with palliative radiotherapy. EORTC 1205, which compared chemotherapy before versus after surgery, did not identify a preferred order. In a 24-patient trial, patients given two immune checkpoint inhibitors before surgery had significantly longer survival than those given one. The authors concluded that combined treatments may provide a survival benefit in selected patients at high-volume specialized centers, but are limited by high morbidity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published trials and studies (literature search of PubMed)
• Who was studied: Published studies and trials of perioperative therapies (radiotherapy, chemotherapy, intraoperative chemotherapy, immunotherapy) in pleural mesothelioma; no new patients were studied
• Exposure: Not studied. The review concerns cancer treatments; asbestos is mentioned only as the main cause of pleural mesothelioma, and no fiber types are discussed.
• Main results:
  • As described by the review, the MARS and MARS 2 randomized trials suggested that adding surgery to chemotherapy may be detrimental compared with chemotherapy alone
  • Operative mortality at 90 days was 8.9% in the MARS 2 trial and 1.7% in the EORTC 1205 trial, where surgery was done only at specialized centers
  • A randomized phase III trial enrolled patients with gross residual disease after non-radical lung-sparing surgery. In that trial, two-year overall survival was 58% with radical hemithoracic radiotherapy versus 28% with palliative radiotherapy.
  • Across reports cited in the review, radiotherapy carried grade 3 to 5 adverse events: pneumonitis 5 to 10%, dermatitis 8 to 17%, esophagitis 10 to 15%
  • In EORTC 1205, which compared chemotherapy before versus after surgery, 21 patients (70%) in arm A and 17 (50%) in arm B met the endpoint for treatment success, among 64 in the primary analysis. The trial did not identify a preferred sequence.
  • In a phase II trial of immune checkpoint inhibitors given before surgery (24 patients), those receiving dual therapy had significantly longer overall and disease-free survival than those receiving monotherapy
  • Evidence on hyperthermic intraoperative chemotherapy was described as limited and largely retrospective
• The authors' conclusion: The authors concluded that multimodal perioperative treatments may provide a survival benefit in selected patients and in high-volume specialized centers, but are limited by high morbidity.
• Limitations the authors state:
  • Comparisons between different trials (such as MARS 2 and EORTC 1205) may introduce bias
  • Radiotherapy evidence is inconsistent because the disease is rare, prospective studies enrolled few patients, and statistical power was low

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, State-of-the-Art Defense, Asbestos Exposure, Prognosis, Chemotherapy, Immunotherapy, Surgical Resection, Overall Survival.

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