Year: 2016
Type: editorial
Abstract: In diseases such as malignant pleural mesothelioma (MPM), in which there is a controversy surrounding the merits of therapeutic intervention, accurate staging of the disease at presentation is imperative. An assessment of the longevity of the tumour and its biological behaviour is key to advising who will benefit from radical surgery. Stage grouping is paramount in the assessment of the long-term outcomes from surgery and too often stage-specific survival is ignored in MPM in favour of overall median survival which may mask subgroups that stand to benefit most. It is well recognized that more clinical trials in MPM are needed but the design or interpretation of these data must be guided by stage. The unusual anatomical situation of MPM creates a problem in assessing the size and location of the primary tumour. The current T descriptors are descriptive rather than numeric and most applicable to surgical and pathological staging [ 1 ]. There is a greater need for pretreatment assessment of stage. The paper by Kircheva et al. [ 2 ] supports the use of tumour dimensions over local relations in staging criteria but their advocacy of tumour weight is only likely to be of use in planning adjuvant therapy. Recent re-evaluation of the IASLC database, presented at the 16th World Conference on Lung Cancer, has suggested the use of tumour thickness as a T-staging variable. This places more emphasis on pretreatment imaging techniques. Tumour volume calculated using a semiautomated computer algorithm [ 3 ] has been shown to be associated with preoperative clinical stage and survival but interobserver variability is a problem for reproducibility [ 4 ], fluorodeoxyglucose-positron emission tomography can offer a functional addition (glycolytic activity) to tumour volume and the total glycolytic volume has been found to be more predictive of survival than tumour, nodes, metastases staging [ 5 ]. While Kircheva et al. [ 2 ] are to be commended for their ingenuity, there are some limitations to their study which detract from their conclusions. The proportion of non-epithelioid MPM in their series at 49% is unusually high for a surgical series and thus makes direct comparison more difficult. While macroscopic complete resection is the accepted goal of extended pleurectomy decortication (EPD), the authors aimed only for maximal debulking accepting a 5% R2 resection. This again may have affected their predictors of survival. The reported incidence of pN0 disease (40%) is somewhat surprisingly low given that 71% of cases were staged pT3/4. One may also question why 15% of cases were staged at pNX, suggesting insufficient nodal material for analysis. There was no mention of the intraoperative nodal dissection technique in the manuscript which suggests that a more rigorous approach may have led to different conclusions. In light of these confounding factors, the authors may have been misguided to play down the relative importance of nodal stage in the prognosis of MPM and thus overstate the importance of tumour volume and weight. Contrary to the conclusions of Kircheva et al. [ 2 ], it is likely that nodal metastasis is indeed key to our current estimation of prognosis in epithelioid MPM. As is evident from their study and from the latest analysis of the IASLC database (as recently presented at the 16th World Lung Cancer Conference), the greater the tumour thickness (or volume), the more likely there will be nodal disease. Quite simply epithelioid MPM should be considered as node-negative or node-positive for clinical management of otherwise resectable disease. The more subtle subdivision into hilar (N1) and mediastinal (N2) lymph node categories considered in non-small-cell lung cancer does not hold true in MPM as there is evidence that the lymphatic drainage of pleura may be directly to the mediastinum [ 6 ] Upfront radical surgery for node-positive disease should be carefully considered and possibly deferred in favour of induction chemotherapy. One could argue that primary EPD is only indicated in biopsy proven node-negative epithelioid MPM. Rather than relying on computed tomography (CT) estimates of nodal size or tumour volume, which are subjective parameters with interobserver variability, histological nodal staging is to be encouraged. This is emphasized by our previously demonstrated finding that malignant involvement cannot necessarily be predicted by nodal size on CT [ 7 ]. Furthermore, there is a ‘gravitational’ hypothesis that suggests that epithelioid MPM progresses from the diaphragmatic pleura to the apex of the chest depending on the pleural fluid as a vehicle of intrapleural dissemination of both inhaled asbestos fibres (in aetiology) and/or shed tumour cells [ 8 ]. Hence, there is worsening prognosis as the tumour involves lymph nodes and surgical margins at superior thoracic levels. This relative importance of upper mediastinal nodes supports the use of endobronchial ultrasound or cervical mediastinoscopy in routine staging prior to radical surgery. Those, who argue that because one cannot assess all nodes there is no argument for mediastinoscopy, should consider that the addition of endoluminal ultrasound staging and the detection of nodal metastases inaccessible to mediastinoscopy had no prognostic benefit [ 9 ]. What is clear is that extensive surgery, without inconsiderable morbidity, is difficult to justify in patients with limited survival hence the need for prognostic assessment. It must be conceded that anatomical staging gives only a ‘snapshot in time’ without recognition of the speed of evolution of the disease or how long the disease has taken to reach that particular extent. In the future, anatomical staging will be superceded by biological markers of outcome [ 10 ] currently under research, the evaluation of which will be obtained in a relatively non-invasive fashion by a blood sample or pleural fluid sample. However, currently, while the research continues, the answer lies in the surgeon taking responsibility for accurately informing the patient of the likely outcome of resection. This implies not only accurate imaging but also invasive preoperative nodal staging and intraoperative systematic nodal dissection. Postoperative assessment of the weight of the resected specimen seems to be a useful adjunct in prospective data collection and with further validation may be used in the prediction of outcome.
DOI: 10.1093/ejcts/ezv436
Author: David A. Waller
Institution: Glenfield Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2346282440