The role of surgery in the management of mesothelioma Mr Martyn Carr Consultant Thoracic Surgeon Liverpool Heart and Chest Hospital

Introduction Incidence increasing Incidence increasing Expected to peak in 2020 Expected to peak in % men born in 1940’s may develop malignant mesothelioma 1% men born in 1940’s may develop malignant mesothelioma Poor prognosis; 5-14 months after symptoms Poor prognosis; 5-14 months after symptoms

Prognostic factors Epithelial variant Epithelial variant Younger age Younger age Good performance status Good performance status Early stage disease Early stage disease Lack of chest pain at diagnosis Lack of chest pain at diagnosis

Surgery for Mesothelioma Diagnostic Diagnostic Palliative Palliative Radical Radical

Diagnostic Thorocoscopy

Diagnosis Percutaneous needle biopsy 40 – 69 % Percutaneous needle biopsy 40 – 69 % Combined with cytology 80 – 90 % Combined with cytology 80 – 90 % Thoracoscopic pleural biopsy 80 – 100% +/- talc Thoracoscopic pleural biopsy 80 – 100% +/- talc

Pre & Post talc pleurodesis

Palliative Surgery Pleurectomy/decortication

Pleurectomy/decortication Patients with comorbid conditions precluding more aggressive surgery (EPP) Patients with comorbid conditions precluding more aggressive surgery (EPP) Advanced disease and clearly unresectable Advanced disease and clearly unresectable Drain and prevent recurrence of pleural effusion Drain and prevent recurrence of pleural effusion Cytoreductive Cytoreductive

Pleurectomy and Decortication Lung left behind Lung left behind Remove all gross evidence of tumour Remove all gross evidence of tumour Pericardium and diaphragm left behind if they can be separated from the pleura Pericardium and diaphragm left behind if they can be separated from the pleura Aim to get the lung fully expanded Aim to get the lung fully expanded Used for palliation and cure Used for palliation and cure

D and P – The Evidence No RCT’s No RCT’s 8 published series 8 published series Median survival 5-17 months Median survival 5-17 months Mortality % Mortality % Morbidity 16-22% Morbidity 16-22%

Pleurectomy/decortication

Pleurectomy/decortication

Radical surgery Extra Pleural Pneumonectomy EPP

Extrapleural Pneumonectomy En bloc resection of ipsilateral pleura, lung, hemidiaphragm, and pericardium En bloc resection of ipsilateral pleura, lung, hemidiaphragm, and pericardium Considerable mortality and morbidity Considerable mortality and morbidity Reserved for fit patients with early disease Reserved for fit patients with early disease

EPP

EPP

EPP

EPP

Patient selection for EPP Epithelial subtype with no extrapleural nodes = EPP Median SR 51 months Epithelial subtype with no extrapleural nodes = EPP Median SR 51 months Sarcomatous, positive extrapleural nodes show no benefit with surgery Median SR < 12 months Sarcomatous, positive extrapleural nodes show no benefit with surgery Median SR < 12 months Sugarbaker et al 1999

EPP – The Evidence No RCT No RCT Series reports only Series reports only Possible survival benefit it certain subgroups Possible survival benefit it certain subgroups Mortality % Mortality % Morbidity 20-60% Morbidity 20-60% 2 year survival rates up to 48% (Sugarbaker) 2 year survival rates up to 48% (Sugarbaker) Median survival months Median survival months 5 year survival of 15% reported 5 year survival of 15% reported

CTC Experience 1 st Nov 2003 to 31st August st Nov 2003 to 31st August 2009

Our Experience Pleurectomy and decortication Pleurectomy and decortication Aim to fully expand lung Aim to fully expand lung Aim to remove disease from chest wall Aim to remove disease from chest wall De-bulk tumour (Cytoreductive Surgery) De-bulk tumour (Cytoreductive Surgery) Diaphragm and pericardium not resected Diaphragm and pericardium not resected Radiotherapy to drain site Radiotherapy to drain site Pre- or post-operative chemotherapy Pre- or post-operative chemotherapy

Age Average of 64 years ( 38-80y)

Histology

46 Decortications

Pre-op Therapy

Distribution of disease

Utilisation HDU

Utilisation ITU 1 patient stayed 15 days: renal failure-HF, empyema, confusion 1 patient stayed 15 days: renal failure-HF, empyema, confusion

Post-op Length of Stay

Morbidity 13 prolonged air leak and 4 patients discharged with drain 13 prolonged air leak and 4 patients discharged with drain 1 patient required bronch for sputum retention 1 patient required bronch for sputum retention 1 Deep wound infection 1 Deep wound infection 1 patient on ITU for 15 days with renal failure-HF, empyema, confusion 1 patient on ITU for 15 days with renal failure-HF, empyema, confusion 2 ITU readmissions 2 ITU readmissions

Mortality 1 Death 1 Death Pneumonia Pneumonia

Survival 34 Deaths 34 Deaths 12 Alive 12 Alive

34 Deaths Mean of 331 days (12 to 1821 days) Mean of 331 days (12 to 1821 days) Median 216 days Median 216 days

12 Alive 2 patients from patients from 2009 The other 10 patients operated between May 2006 and Nov 2008, survived 304 to 1224 days, Median 646 days The other 10 patients operated between May 2006 and Nov 2008, survived 304 to 1224 days, Median 646 days

Conclusions Pleurectomy and decortication can be performed safely with an acceptable mortality and morbidity Pleurectomy and decortication can be performed safely with an acceptable mortality and morbidity Patients appear to get palliation from the operation in terms of chest wall pain and shortness of breath Patients appear to get palliation from the operation in terms of chest wall pain and shortness of breath

Current UK Trials Treatment with or without radical surgery for mesothelioma (MARS) a randomised trial comparing extra-pleural pneumonectomy (EPP) against no EPP surgery within the context of trimodality therapy (chemotherapy, surgery, post- operative radiotherapy). Treatment with or without radical surgery for mesothelioma (MARS) a randomised trial comparing extra-pleural pneumonectomy (EPP) against no EPP surgery within the context of trimodality therapy (chemotherapy, surgery, post- operative radiotherapy). MARS2 to include chemotherapy +/- pleurectomy/decortication MARS2 to include chemotherapy +/- pleurectomy/decortication

Surgery for Mesothelioma After Routine Therapy (SMART) Mesothelioma and decortication Mesothelioma and decortication T1 – 3, N0 – 1, M0 T1 – 3, N0 – 1, M0 Alimta and Cisplatin Alimta and Cisplatin Randomised to +/- decortication Randomised to +/- decortication QOL and survival QOL and survival

SMART Multicentre – LHCH, Blackpool and Wythenshawe Multicentre – LHCH, Blackpool and Wythenshawe 20 patients in each group 20 patients in each group Observation could have surgery Observation could have surgery CT scans and QOL questionaire CT scans and QOL questionaire

SMART Local tumour control rates Local tumour control rates Time until first documented relapse Time until first documented relapse Overall survival Overall survival Cost effectiveness Cost effectiveness

Conclusions Increasing incidence with need for a more aggressive surgical approach Increasing incidence with need for a more aggressive surgical approach Surgery as part of a multimodality regime Surgery as part of a multimodality regime