Satya Shanbhag Waikato Cardiothoracic Unit Meso-VATS Trial Satya Shanbhag Waikato Cardiothoracic Unit

Introduction Malignant pleural mesothelioma (MPM) has consistent worse prognosis Treatment modalities limited: chemo, EPP and combined therapy VATS debulking with partial pleurectomy emerging option Usual symptom control through talc pleurodesis

Rationale The MesoVATS trial was designed to establish whether 1) VAT-PP improves survival in patients with pleural effusion secondary to malignant pleural mesothelioma when compared with talc pleurodesis, 2) to provide a full economic analysis of these treatments, 3) and to compare symptom control and quality-of-life outcomes.

Methods Patients randomly assigned to undergo VAT-PP or talc pleurodesis(June 2003 –Dec 2012) Study in 12 centers from UK (Main center: Papworth) F/U period up to 1 year (1,3,6 and 12 months) Primary Outcome: Overall survival after 1yr after randomisation Secondary Outcome: Pleural effusion, quality of life, exercise tolerance and cost to health service

Methods Pts randomised in 1:1 fashion by computer generated block of 10pts Randomisation stratified according to risk score ( high WCC, non-epitheloid cell type & male sex) Staging determined by 2 radiologists using IMIG score Estimated 1yr survival to be 37 with TP and 59% with VATS-PP respectively (80% power- 196 pts)

Survival

Quality of Life post procedure

Cost per procedure

Author Conclusions First RT study about VAT-PP and talc pleurodesis for MPM At 1yr no difference in primary outcome between the two group VATs-PP resulted in more complications, longer hospital stay and was expensive

Study strengths Well conducted multi institutional randomised study The study met the required number of patients Some amount of blinding performed for selection Published in a reputed journal

Study weakness Very few patients to compare at 1 yr, logical conclusion cannot be drawn Combination therapy not standardised, left to the treating Hospital Because of diminishing number of patients, secondary endpoints could be deducted from about 40% of patients

Study weakness Overall survival chosen as primary endpoint for an operation where the tumour remained Varying degree of debulking introduced heterogeneity to the study Additional confounders: neoadjuvant therapy in some and also change in method of talc introduction Treatment not stratified for tumour stage or volume

Mesothelioma & Radical Surgery (MARS Trial) UK Trial from 2003-2008 with 50 patients randomised (24 EPP and 26 no EPP) Three early mortality in EPP group with a HR of 2.75 compared to non EPP group Weakness: Small study, very far reaching conclusions Investigator Conclusion: In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients

MARS2 Trial Randomisation between chemotherapy only and extended pleural decortication (EPD) Trial still ongoing recruiting total of 50 patients. Completion by end of this year Early results favour surgery over chemotherapy arm

What are the evidence/guidelines?

Future Progress

Conclusions EPP has a role in mesothelioma patients who have a favourable early stage tumour These should be offered for the ideal candidate patients Multi-modal therapy has better outcome compared to monotherapy/surgery Talc pleurodesis is adequate for advanced stage cancer for symptom relief Newer treatment modalities/surgery devised for prolonging life and quality