Malignant pleural mesothelioma (PM) is typically viewed as an incurable cancer with poor prognosis, yet long-term survivors exist. The goal of this study was to characterize patients with PM and identify prognostic factors distinguishing them from short-term survivors.
The analysis included patients treated between 1998 and 2015 from eight global high volume PM institutions. Retrospective, 276 long-term survivors (defined as surviving more than 5 years post-surgery) treated at high-volume mesothelioma centres were identified. All underwent multimodality therapy, which included macroscopic complete resection. A matched control group of 333 patients, including 238 short-term survivors (survival <2 years), was compared using conditional logistic regression.
The median overall survival was 99 months (over 8 years). 89% had epithelioid histology and asbestos exposure was known in 53.5%. The disease was right-sided in 56.5% of cases
Surgery type included extended pleurectomy/decortication (49.6%), extrapleural pneumonectomy (43.2%), pleurectomy/decortication and partial pleurectomy. 70.3% received systemic chemotherapy (30.9% neoadjuvant, 39.4% adjuvant) and 39.5% received adjuvant radiotherapy.
When comparing long-term and short-term survivors, the long-term survivors were more likely to be female, younger, have epithelioid histology, lower ECOG scores, and lower white blood cell count (WBC). In addition, WBC was a significant predictor of survival. Asbestos exposure and biphasic histology were associated with worse outcomes.
The prognostic implication which seems critical is patient selection and multimodal treatment. Long-term survivors typically had favorable clinical profiles, including early-stage disease (T1-2, N0), better functional status, and surgery (EPD or PD). The importance of biological and staging precision was emphasized, with future prognostic models suggesting inclusion of tumor volume and spatial heterogeneity.
Interview with Prof. Dr. med. Isabelle Opitz and PD Dr. med. Olivia Theisen-Lauk (Zürich)
What inspired you to conduct this study?
PM is a devastating disease with very low survival rates globally. As a high-volume and highly specialized center with long-standing experience in PM, we consistently observe a subset of long-term survivors – beyond 5 years, which is exceptional for PM - when surgery is part of the treatment concept. This stands in contrast to recent data—such as the MARS 2 trial—which questions the surgical approach due to its invasiveness and limited survival benefit at the population level. With this study, we aimed to analyze this by identifying and characterizing these long-term survivors, offering a real-world perspective on the value of surgery in carefully selected patients treated a high volume centers around the globe.
Were there any unexpected findings?
Among the 276 patients included, 63 presented with pT2 and 90 with pT3 tumors, indicating that long-term survival can be observed even in more advanced stages of pleural mesothelioma. Interestingly, we were unable to identify clear prognostic factors that distinguished long-term survivors from the remainder of the cohort. This lack of identifiable influencing variables highlights the heterogeneity of the disease and emphasizes the importance of further studies to refine patient selection and to clarify the role of surgery in advanced-stage disease.
What is the direct impact on the surgeon's work?
This study provides data that support treatment allocation within multidisciplinary tumor boards, particularly regarding the integration of surgery into multimodality treatment strategies. Rather than challenging established guidelines, our findings refine the basis for patient selection and highlight the role of surgery as part of individualized therapeutic concepts.
What is your learning point from this project?
Our key learning was the importance of combining clinical intuition with structured data analysis. It reinforced how multidisciplinary collaboration, and the critical reevaluation of established practices can drive meaningful progress. Most importantly, this project confirmed that long-term survivors do exist—even in a disease as aggressive as pleural mesothelioma. For those patients, it is worth continuing to push research forward, to better understand the underlying factors and ultimately design more refined and effective treatment concepts.
Are there any subsequent projects planned?
Yes, the next step will be the development of further clinical trials based on different multimodal treatment concepts. In particular, the integration of immunotherapy into surgical pathways is a promising avenue, as is the advancement of intrathoracic therapies such as intracavitary drug delivery. These approaches hold potential to improve patient outcomes and refine the role of surgery within evolving therapeutic strategies. Our goal is to translate the findings of this retrospective study into prospective frameworks that can be tested and validated in a broader clinical context.
