This economic analysis simulates the clinical scenario of a patient with known or suspected NSCLC. The validity of any model and its conclusions can only be verified by prospective trials. For this reason, we relied on the majority of our parameter values from the only prospective trial to date comparing the performance of EUS FNA, EBUS FNA, TBNA and combinations of these tests.[57
] The findings illustrate that the least costly approach of investigating these patients is predicated on the pre-test probability of malignant mediastinal lymph nodes; below a malignant nodal probability of 32.9%, initial EUS FNA is the preferred option. However, above this probability combined approach with EUS FNA and EBUS FNA is optimal.
How relevant is our decision model in facilitating patient management? The medical literature demonstrates that 22% to 30% of patients with NSCLC have enlarged mediastinal lymph nodes detectable on CT at the time of presentation.[53
] In the presence of enlarged nodes on CT, the pre-test probability of malignant nodal involvement raises to 60-70%,[58
] while in the absence of visualized nodes on CT, the pre-test probability of malignant nodal involvement declines to 10-30%.[59
] Therefore, the findings of this economic analysis illustrate that the clinician can tailor their approach depending on the CT findings. Enlarged mediastinal nodes on CT would favor initial combined EUS FNA and EBUS FNA while absence of nodes on CT favors initial EUS FNA alone.
Several limitations of this study are noteworthy. As with any decision analysis model, it is of most use when considered as a guide in patient management rather than a substitute for sound clinical judgment. For example, in the setting of a very high pre-test probability of mediastinal nodal malignancy, it may be most appropriate to repeat a minimally invasive technique (e.g., EUS FNA) after one negative result prior to proceeding to thoracotomy. Second, the robustness of any model depends on the assumptions used. In this model, the specificity of all sampling procedures is considered perfect. In clinical practice, the unlikely event of obtaining a false positive biopsy result would lead to erroneous over-staging of a patient, thereby depriving a potentially resectable patient of a chance at curative surgery. This is a theoretical limitation of all the sampling modalities (EUS FNA, TBNA, EBUS FNA and mediastinoscopy). However, for practical purposes, the possibility of imperfect specificity (i.e., the interpretation of a benign cytology specimen as malignant) was considered to be exceedingly low and did not justify confirmatory thoracotomy in all patients with a positive FNA result. Related to the analysis, this means that the essential impact to the model of any deviation from perfect specificity is negligible. That is, in terms of the model the expected cost calculated as the product of the small, but nearly zero, probability of a false positive times the expected consequent cost, a large value if the false positive occurred, would be negligible.
Our cost analysis was based on estimate of accuracy from our own clinical trial, one of the only which has directly compared EUS, EBUS, and bronchoscopy. Our accuracy estimates are somewhat lower than other published meta-analyses.[57
] In order to ensure that our results are robust, we performed the cost analysis across a wide range of accuracy estimates for EUS and EBUS and found that the conclusions held within the range of all published values.
Although both EUS FNA and EBUS FNA were modeled as separate choices, the favorable performance of EUS FNA and EBUS FNA in combination, illustrates the complementary nature of these 2 modalities. The incremental sensitivity of both in combination over each individually reflects the differing abilities of both tests to detect lymph nodes in differing stations of the mediastinum. EUS functions best at accurately detecting mediastinal lymphadenopathy in the subcarinal (station 7), aortopulmonary window (station 5), left paratracheal (station 4L), and paraesophageal (station 8) regions[24
] while its ability to adequately visualize the upper anterior lymph node stations (1 through 3 and 4R) is compromised due to interfering tracheal air. Conversely, EBUS has excellent ability in detecting the upper anterior nodal stations.[54
] This complementary nature of EUS and EBUS in providing views of all portions of the mediastinum between them, translates into lower expense when evaluating patients with a higher pre-test probability of nodal involvement. In the future, it may be possible to identify subgroups of patients that only require a single procedure. This would even further reduce to cost of endoscopic staging and improve cost-effectiveness.
Our study is limited to an analysis of invasive staging procedures. Other groups have previously analysis the cost effectiveness of non-invasive staging including CT and PET and generally found it to be cost effective[63
Finally, there is increasing evidence that genomic characterization of lung cancer, particularly, K-ras and EGFR status, may serve as a guide to therapy. EUS-FNA is well positioned to obtain tissue suitable for DNA and RNA extraction suitable and thus has the capacity to provide this valuable information.[64
The utility of nodal sampling techniques in patients with known or suspected NSCLC includes their impact on clinical decision making and also their conversion of a major inpatient surgery to a minimally invasive outpatient procedure in an appropriate subset of patients. Because the preferred choice of initial test (EUS FNA or combined EUS FNA and EBUS FNA) is highly sensitive to pre-test probability of malignant mediastinal lymph nodes, detection of enlarged nodes on thoracic CT is an important element in guiding further test selection.