Malignant Pleural Mesothelioma
Overview
Malignant Pleural Mesothelioma is a malignant tumour involving the pleura (lining of lung), induced by asbestos exposure in most cases. There are more than 2,700 new cases diagnosed each year in the United Kingdom, around 1000 in France and 200 in Switzerland. Thousands of cases are also diagnosed each year in the USA and Canada. The median survival for patients with mesothelioma is thought to be around 12 months (UK National Mesothelioma Audit 2018). Recent reports show that with an aggressive approach called multimodality therapy up to 33% of patients with early-stage disease can survive for five years or more. Research in Malignant Pleural Mesothelioma is progressing and new drugs have become available in the past decade, which have significantly increased life expectancy.
Diagnosis of Malignant Pleural Mesothelioma
The diagnosis of Malignant Pleural Mesothelioma is sometimes obvious in view of a chest X-ray or computed tomography (CT). In most cases, there will be a large fluid collection in the chest cavity. In some patients, there is solid tumour surrounding the lung and infiltrating the surrounding structures (ribs, diaphragm, spine, …). However, other pleural cancers can mimic mesothelioma and the diagnosis has to be established by analysing formally some pleural tissue. In less than 10% of patients, the diagnosis will be made on pleural fluid aspirated through a simple needle. Most patients with this condition now benefit from a VATS (thoracoscopic) pleural biopsy to establish the diagnosis and a VATS pleurodesis to prevent the re-accumulation of fluid around the lung. A small camera is introduced inside the chest and multiple biopsies are taken from the pleural cavity. Generally, sterile talc is insufflated inside the chest cavity to promote inflammation and prevent fluid re-accumulation. A chest tube is inserted and kept for 2-4 days after the procedure, then removed when drainage has settled. Alternatively, a small indwelling pleural catheter is placed in the chest cavity and secured to the skin to allow for further drainage of the fluid at home, by a nurse. When fluid is absent, an open pleural biopsy can be performed by the surgeon under general anaesthetic. When there is a big bulk of tumour, tissue can be obtained through a special biopsy needle under computed tomography (CT) or Ultrasound guidance (using local anesthesia).
Pleural biopsies are analysed by a specialist pathologist who will produce a report mentioning the type (and eventually subtype) of mesothelioma. Schematically, there are three main types: epithelioid, biphasic and sarcomatoid. The epithelioid type is generally associated with a better prognosis and long-term survivors are generally patients with epithelioid tumours. Sarcomatoid mesothelioma is a very aggressive type, which is usually resistant to chemotherapy and associated with short survival. However, recent trials have showed that immunotherapy is generally active on sarcomatoid mesothelioma and we have seen patients experience good responses and enjoy longer survival. Biphasic mesothelioma is a combination of epithelioid and sarcomatoid mesothelioma which is usually associated with an intermediate prognosis. It seems that biphasic mesothelioma is also quite sensitive to new immunotherapy drugs (pembrolizumab, nivolumab, ipilimumab).
In the past few years, it has been formally established that mesothelioma can occur as part of a multi-cancer syndrome due to familial genetic mutations (BAP-1 syndrome). In addition, some patients can present de novo mutations making their DNA repair more difficult and predisposing to several types of cancer including mesothelioma. Prognosis for patients suffering those genetic alterations can be different and treatment can be personalized as well as follow-up and family counselling. As we have always wanted to be at the forefront of diagnostic techniques, we and our colleagues started offering routine genomic testing to our mesothelioma patients more than 10 years ago. This approach has proved very useful and we have been able to offer innovative therapies to patients who would otherwise not be offered therapeutic options.
Treatment of Malignant Pleural Mesothelioma
The treatment of pleural mesothelioma is based on chemotherapy, immunotherapy and occasionally radiotherapy for most patients.
Chemotherapy involves three-weekly outpatient visits where drugs are injected intravenously over a few hours. Depending on the tolerance and response to treatment, the number of injections (cycles) may vary from two to more than six.
For patients with early stage mesothelioma and a good general condition, multimodality therapy is often considered. Multimodality therapy often includes chemotherapy, immunotherapy, radical surgery aiming at removing all the tumour and radiotherapy.
Extrapleural pneumonectomy (EPP) is a major operation consisting in the removal of the tumour together with the all lung, pericardium (lining of heart) and diaphragm. This radical procedure was evaluated in the MARS trial which suggested it was potentially detrimental. Professor Lang-Lazdunski operated on more patients than any other surgeon involved in the MARS trial and stopped performing EPP for mesothelioma in 2008. Since 2004, he has been performing pleurectomy/decortication with hyperthermic povidone-iodine pleural lavage, with excellent results. He has showed that the later operation was associated with lower mortality and less complications than the previously performed extrapleural pneumonectomy (EPP). Several prominent mesothelioma surgeons have adopted his technique around the world.
Recent publications have emphasized the importance of preserving the lung. Most mesothelioma surgeons now offer an alternative procedure known as pleurectomy / decortication (P/D) consisting in the surgical removal of the involved pleura, but sparing of the lung. This procedure allows re-expansion of the lung and prevents fluid re-accumulation in the chest cavity, improving thereby patients’ quality of life.
Depending upon the tumour type, stage and the completeness of removal, 1 in 3 patients receiving multimodality therapy can live five years and beyond according to recent publications.
At Clinique de Genolier, our team provides a full service for this condition including radiotherapy, chemotherapy, immunotherapy, minimally-invasive surgery (VATS pleural biopsy and talc pleurodesis, insertion of indwelling pleural catheter), and multimodality therapy involving pleurectomy / decortication. We also refer patients for clinical trials when appropriate and when patients wish to have access to new therapies.
Professor Lang-Lazdunski has accumulated a very large experience with these operations and our anaesthetists and critical care physicians are used to look after patients following these complex procedures. In the past 20 years we have not had any mortality after radical Pleurectomy / Decortication in more than 150 patients. This is the lowest mortality reported worldwide. More than 96% of our patients were able to receive chemotherapy or / and targeted therapy after surgery and the vast majority of them returned to normal activities after a few weeks. Many of our patients go on to receive personalized targeted therapy or/and immunotherapy after successful first-line chemotherapy, allowing them to survive for 5 to 10, or even 15 years.