Statistics from Altmetric.com
A new tool in lung cancer staging
The management of lung cancer depends to a great extent on its histological type and the stage of disease. Although most patients with non-small cell lung cancer (NSCLC) have advanced disease at presentation, approximately 30% have tumour confined to the lung and locoregional lymph nodes. For these patients surgery offers the best hope of a cure. Despite apparent complete resection, 5 year survival rates after surgery are approximately 40–50%.1 This highlights the importance of accurately staging lung cancer to determine resectability and provide prognostic information.
In clinical practice a presumptive diagnosis and stage are based on presentation, risk factors, and radiological appearances—particularly CT scans. Obtaining a histological diagnosis and confirming the stage of the disease often take place at the same time. One of the most difficult tasks is accurate staging of nodal involvement in the mediastinum.
It is reported that mediastinal lymph nodes contain metastatic disease in 28–38% of patients with NSCLC at the time of diagnosis.2 Traditionally, CT scanning has been used to assess mediastinal lymph node involvement. Lymph nodes greater than 1 cm in short axis diameter are considered abnormal and suggest involvement. However, CT detection of lymph node spread has sensitivity and specificity rates of 61% and 79%, respectively.3 Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) is more accurate in identifying mediastinal lymph node involvement. FDG-PET in combination with CT scanning has been shown to further improve sensitivity and specificity rates in detecting lymph node involvement,3 but in much of Europe—and particularly in the UK—it is not widely available for the routine staging of lung cancer.
The generally accepted practice has therefore been that enlarged lymph nodes seen on CT scans should be investigated further and, in most instances, this is performed by mediastinoscopy. Although currently considered the gold standard in mediastinal staging, mediastinoscopy has some drawbacks. Mortality in experienced centres is negligible but morbidity rates (mainly arrhythmias) are reported to be 0.5–1%.4 Mediastinoscopy involves a general anaesthetic and in most UK centres requires an overnight stay in hospital. Not all lymph node stations are accessible via the standard cervical approach, including those in the aortopulmonary window (stations 5 and 6) and the lower mediastinum (8 and 9).4,5
Other tools are available to stage the mediastinum including mediastinotomy, transbronchial needle aspiration (TNBA) or Wang needle biopsy, with or without ultrasound guidance, transthoracic needle aspiration (TTNA), and endoscopic ultrasound guidance for fine needle aspiration (EUS-FNA).
Anterior mediastinotomy, also known as the Chamberlain procedure, involves an incision in the second or third intercostal space just to the left of the sternum. This method is useful for visualising nodes in the aortopulmonary window. Left upper lobe tumours frequently metastasise to these nodes and, for this reason, they are the most important group of nodes not accessible by standard cervical mediastinoscopy. Video assisted thoracoscopy (VATS) has also been used to assess some lymph node stations not accessible by mediastinoscopy.4,5 Both VATS and anterior mediastinotomy require a general anaesthetic and, in most cases, an overnight stay in hospital.
TBNA is used in many centres to obtain tissue from subcarinal and hilar lymph nodes. While it is possible to obtain a diagnosis from paratracheal lymph nodes, it is technically more difficult because of the inability to angle the bronchoscope and the needle sufficiently. Conventional TBNA is a “blind” procedure with placement of the needle guided by landmarks from the radiographic appearance alone. Diagnostic yield varies widely among inexperienced and experienced operators.
Endobronchial ultrasonography (EBUS) is a fairly new technique. It has previously been used to determine the depth of tracheobronchial invasion.6 Recent studies have examined the value of EBUS in determining metastatic involvement of mediastinal and hilar lymph nodes.7,8 These studies were small and were not controlled. It is therefore not yet possible to say whether EBUS-TBNA provides a higher yield than TBNA alone.
The paper published by Kramer et al in this issue of Thorax describes in detail their experience of EUS-FNA in mediastinal staging and proposes that the wider uptake of this method of staging could reduce the number of surgical procedures required.9 They enrolled 81 patients with suspected or pathologically confirmed lung cancer in whom PET scans had shown activity in the mediastinum, but who were otherwise deemed to be surgically resectable. All patients were then investigated by EUS with or without FNA. No complications were reported. A positive diagnosis of malignancy was achieved in 50 of 81 patients (62%) using EUS-FNA alone. The remaining patients underwent an additional surgical staging procedure. A negative or inconclusive EUS-FNA result did not reliably exclude malignancy as 68% (19/31) of these patients were found to have lymph node involvement when staged by additional methods. The authors argue that, if EUS-FNA was routinely used to stage patients with enlarged mediastinal lymph nodes, 62% of these cases could be spared the need for mediastinoscopy or explorative thoracotomy. They have estimated that use of a staging algorithm with EUS-FNA could reduce the average staging cost from $3514 to $2101 per patient.
While these results are encouraging, it is important to understand the limitations of EUS-FNA. As with mediastinoscopy, not all lymph node stations can be viewed. EUS-FNA is particularly helpful for inferior pulmonary ligament, subcarinal and aortopulmonary window lymph nodes. The pretracheal and paratracheal lymph nodes are harder to visualise because of air in the trachea. This makes EUS-FNA of limited value for these lymph node stations. This study confirms that the lymph nodes most commonly involved in lung cancer are the paratracheal nodes (stations 2 and 4), the subaortic nodes (station 5), and the subcarinal nodes (station 7). It shows that, even with an experienced operator, abnormalities in the paratracheal areas were only identified in a very small proportion of cases compared with those seen in the subaortic and subcarinal areas.
Kramer et al also examined the difference between experienced and inexperienced operators. The trainees performed 25 and 29 procedures each. The numbers of abnormal mediastinal lymph nodes detected failed to reach the numbers detected by the more experienced operator. It seems reasonable to assume that the high diagnostic rate described in this paper would be lower in centres which lack the same degree of experience.
Furthermore, all patients enrolled in the study were initially staged by FDG-PET scanning. Unfortunately, this facility is still not widely available in Europe. It is unclear what the accuracy of EUS-FNA would be if CT scanning was the only radiological tool used in the staging work up. Currently, this practice is only available at a small number of institutions, but as this study and others have shown the value of this procedure in the staging of lung cancer, we hope that it will become more commonplace in the future. It is envisaged that EUS-FNA and other techniques such as EBUS will not replace but will complement surgical techniques like mediastinoscopy. The caveat to this is that both EUS-FNA and EBUS have poor negative predictive value and, as such, further staging investigations are required for lymph nodes that have been identified as suspicious on radiological grounds but in which EUS-FNA has been negative or inconclusive for malignancy.
In conclusion, Kramer et al have shown that EUS-FNA is a well tolerated and safe procedure that obviates the need for general anaesthesia or hospital admission. It can be used to diagnose lymph node involvement and, as such, can reduce the number of surgical staging procedures required and reduce costs. Perhaps most importantly, it may alleviate some of the burden on that scarce resource—the thoracic surgeon!
A new tool in lung cancer staging