Lung cancer is the most common cause of cancer deaths in the western world. The treatment of lung cancer depends on tumor histology and pathologic stage. In non-small cell lung cancer (NSCLC), complete surgical resection is the only chance of cure. Because the benefits of surgery are largely limited to patients with stage I and II NSCLCs, accurate staging is essential in every case. Imaging studies such as chest computed tomography and positron emission tomography scan frequently reveal mediastinal lymph node enlargement in patients with NSCLC. However, the decision to perform or deny surgery cannot be made on the basis of imaging studies, and pathologic mediastinal staging is essential in every case. Mediastinoscopy is widely accepted as the gold standard for evaluation of nodal disease.1 However, the procedure has several limitations. The reported sensitivity of mediastinoscopy is 80% to 90%.2 Several lymph node stations such as posterior subcarinal nodes (station 7), aortopulmonary window nodes (station 5), and inferior mediastinal nodes (stations 8 and 9) cannot be sampled with cervical mediastinoscopy. In one study, nearly 15% of lung cancer patients considered surgically curable on the basis of staging mediastinoscopy had unsuspected mediastinal lymph node involvement on thoracotomy.3 The procedure is invasive, costly, and needs general anesthesia. Over past 2 decades, several less invasive and less expensive alternatives for mediastinal staging have emerged. Among these, transbronchial needle aspiration (TBNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are of greatest interest to the practicing pulmonologists.
Several studies have shown that standard TBNA is a useful and cost-effective alternative to mediastinoscopy in selected patients.4,5 The procedure has high yield for certain lymph node areas such as right paratracheal (2R, 4R), and subcarinal (station 7). Unfortunately, pulmonologists have been slow to embrace this technique, in part owing to the lack of training, and in part owing to discomfort with the “blind” nature of the technique.6 In recent years, several groups of investigators have reported a high success in mediastinal staging with EBUS-TBNA. The initial studies were performed using a miniature 20-MHz radial ultrasound probe to locate the enlarged lymph nodes, but it did not allow real-time imaging during the TBNA procedure.7 Real-time guidance during TBNA is now possible with the availability of a convex-probe endobronchial ultrasound attached to the tip of the flexible bronchoscope. Centers that have pioneered this technique have reported 90% to 95% sensitivity for mediastinal staging with real-time EBUS-TBNA.8,9 The technique seems to have great promise in mediastinal staging of patients with lung cancer.
However, before incorporating any technology in clinical practice, it is important to show that it offers clear advantage(s) over the existing techniques, and that it is cost-effective. No study has directly compared the yield of standard TBNA with that of real-time EBUS-TBNA, but in uncontrolled studies, real-time EBUS-TBNA seems to have higher diagnostic yield than that reported with standard TBNA. Another apparent advantage is high success in sampling smaller lymph nodes and in sampling lymph nodes located in stations where standard TBNA is not applied. However, the upfront cost of real time EBUS-TBNA is higher than the cost of standard TBNA. Therefore, it is fair to ask whether or not it is cost effective to perform real-time EBUS-TBNA in place of standard TBNA for mediastinal staging.
In the January issue of the Journal, Kunst and coworkers10 compare the cost of 5 different strategies for mediastinal staging in patients with lung cancer. The authors report that the most cost-effective approach to stage mediastinum is to first perform standard TBNA. If the results of standard TBNA are negative, real-time EBUS-TBNA is performed next. Mediastinoscopy is performed if both standard TBNA and EBUS-TBNA yield negative results. With this approach, very few patients require mediastinoscopy for pathologic staging. Their results remain robust for a cost range of ±10%.
At a glance, the conclusions seem reasonable, but several issues need further consideration before a cost-analysis of this sort can be applied in policy decision or actual clinical practice. First, the authors assume that all patients with lung cancer who show enlarged mediastinal lymph nodes on initial computed tomography have mediastinal metastasis. In actual clinical practice, many patients with lung cancer have reactive lymph nodes without histologic evidence of metastatic spread. Studies have revealed 28% to 75% prevalence of mediastinal lymph node involvement with the tumor in lung cancer patients.2 With the staging scheme suggested by the authors, the cost of mediastinal staging would be very different for patients with different prevalence of tumor in mediastinal lymph nodes. For instance, when the cost data from this study is applied to a group of patients with a 40% prevalence of tumor involvement in the mediastinal lymph nodes, the cost of staging per patient will be 1414€ when standard TBNA is followed by mediastinoscopy; 1696€ when TBNA is followed by real time EBUS-TBNA, which if negative is followed by mediastinoscopy; and 1620€ if mediastinoscopy is performed as the initial test on all patients. Second, the choice of staging technique also depends on a number of other factors. For example, results of imaging studies such as positron emission tomography scan, availability of endoscopic ultrasound-guided fine needle aspiration, and rapid on-site evaluation of the sample have important role in mediastinal staging when applied in appropriate setting.11–13 The authors did not include any of these in their staging scheme and cost-effectiveness analysis. Finally, it is important to recall that high sensitivity with real time EBUS-TBNA used in this study largely comes from centers with extensive experience with this technique. It is unclear if the beginners will achieve the comparable results.
The optimal approach to mediastinal staging remains a complicated and difficult issue. There is a rapid growth in minimally invasive techniques such as TBNA, real time EBUS-TBNA, and endoscopic ultrasound-guided fine needle aspiration for mediastinal staging of lung cancer patients. Although, negative results from these methods do not obviate need for further surgical staging, their application in carefully selected patients reduces the need for mediastinoscopy. However, from cost-effectiveness standpoint, no single approach is clearly superior to other when applied to an unselected patient population. In an individual case, the approach to pathologic mediastinal staging will depend on the size and stations of enlarged lymph nodes, and availability of local expertise. In this regard, the paper by Kunst and coworkers is a timely reminder that physicians must choose the most cost-effective approach for this purpose.
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