Extrapleural Pneumonectomy After Radiation Produced Durable Survival and Was Considered Safe for Malignant Pleural Mesothelioma


Data published in The Lancet Oncology investigating patients with malignant pleural mesothelioma determined that surgery for mesothelioma after radiotherapy, or SMART, can produce positive early- and long-term effects.

Utilizing extrapleural pneumonectomy after radiotherapy is possible and can produce positive early- and long-term effects for patients with previously untreated malignant pleural mesothelioma, according to data published in The Lancet Oncology.

However, even if surgery for mesothelioma after radiotherapy (SMART) is possible, the research team warned that it is technically demanding to minimize grade 4 adverse events on the protocol and has the potential to impact survival beyond the post-operative period.

“SMART has achieved the best results in a large prospective surgical trial for malignant pleural mesothelioma in terms of overall survival,” wrote the investigators. “However, SMART requires surgical and radiation expertise to achieve optimal results and should not be adopted outside of expert centres with substantial surgical experience.”

The studied population included 96 eligible patients treated with SMART on protocol between November 1, 2008, and October 31, 2019. After completion of intensity modulated radiotherapy, extrapleural pneumonectomy was conducted at a median of 5 days (range 2-12 days).

Looking at the adverse events profile, 47 (49%) patients had 30-day perioperative grade 3/4 events, with 1 patient dying within 30 days of a grade 5 pneumonia.

The 5-year cumulative incidence of local and distant recurrence was 17 (20.1%; 95% CI, 11.4-28.8) and 62 (63.3%; 95% CI, 52.3-74.4), respectively, after a median follow-up of 46.8 months (interquartile range, 13.4-61.2). Specifically, the contralateral chest (46%) and the peritoneal cavity (44%) were recorded as the most common first sites of recurrences in 72 patients.

“The results emphasise the importance of patient selection. [Thirty]­day grade 4 complications are an independent factor affecting long­term survival after extrapleural pneumonectomy, even though most patients survived their complications,” wrote the investigators. “Although careful patient evaluation and selection for extrapleural pneumonectomy is obvious, the detrimental effects of grade 4 complications on overall survival had not been reported previously, and might explain the variable outcomes between surgical series.”

This single-center, phase 2 trial (NCT00797719) recruited patients 18 years or older with an ECOG performance status of 2 or less and resectable cT1–3N0M0 disease with previously untreated malignant pleural mesothelioma.

The primary end point of the study was feasibility defined as the “number of patients with 30-day perioperative treatment-related death (grade 5 events) or morbidity (grade 3 or 4 events).” The main secondary end point of the study was the cumulative incidence of distant recurrence.

A main limitation of this research included the lack of quality-of-life data collected. More, the research team admits that their analysis of grade 4 toxicities from randomization is better suited as a landmark analysis 30 days after.

“Despite these results, extrapleural pneumonectomy has not been widely adopted,” wrote the investigators. “SMART remains an outlier; other studies have not consistently shown a similar survival advantage with extrapleural pneumonectomy.”


Cho BCJ, Donahoe L, Bradbury PA, et al. Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial. Lancet Oncol. 2021;22(2):190-197. doi:10.1016/ S1470-2045(20)30606-9

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