Systematic Endobronchial Ultrasound-guided Mediastinal Staging Versus Positron Emission Tomography for Comprehensive Mediastinal Staging in NSCLC Before Radical Radiotherapy of Non-small Cell Lung Cancer

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/ CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC. In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy ( systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT. Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1–5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%–51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7–9) versus 12 mm (range 6–21), P1⁄4 0.005. acy L. Leong, FRA ose, MBBS, id L. Ball, FRANZCR, and Louis B. Irving, FRACP mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free. (Medicine 95(8):e2488) Abbreviations: EBUS = endobronchial ultrasound, EUS = endoscopic ultrasound, FDG-PET = fluorodeoxyglucose positron emission tomography, LN = lymph node, NPV = negative predictive value, NSCLC = non-small cell lung cancer, TBNA = transbronchial needle aspiration. INTRODUCTION A ccurate mediastinal staging of nonsmall cell lung cancer (NSCLC) is critical for determination of optimal treatment strategies. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused with computed tomography (PET-CT) imaging is routinely used for noninvasive staging of patients with suspected or known NSCLC, although mediastinal abnormalities on PET-CT require invasive confirmation due to the limited diagnostic accuracy of PET-CT. Thoracic surgical guidelines identify mediastinal sampling as being selective (involving only selected suspicious nodes), or systematic (exploration and biopsy of a standard set of lymph node [LN] stations in each case). For patients with early-stage (Stage I and II) NSCLC, guidelines recommend systematic intraoperative mediastinal LN sampling or complete mediastinal LN dissection (Grade 1B) to accurately assess the pathologic stage, which is critical to direct adjuvant therapy. Consequently, at completion of therapy, the pathologic extent of disease is discretely defined for surgical patients. In contrast, although invasive pathologic confirmation of mediastinal NSCLC disease is recommended before radical intent radiotherapy ( systemic chemotherapy), there is no consensus regarding the extent to which pathologic evaluation of the mediastinum should be performed. Thus, although pathological confirmation of mediastinal LN involvement is recommended before radical radiotherapy (with or without chemotherapy), in contrast to surgical candidates, comprehensive staging of the mediastinum is not routinely performed in s is potentially clinically significant, as, egativeand positive-predictive value of eatment fields are generally constructed www.md-journal.com | 1 on the basis of PET-identified disease extent. Sensitivity of PET/CT is even poorer when individual nodal stations are considered separately. Hence, any false-positive nodal activity will result in an unnecessarily extensive field of radiation with consequent greater risk of toxicity, whereas PEToccult nodal metastases will result in the risk of geographic miss, increasing the likelihood of local disease recurrence. Thus, accurate pathologic characterization of the mediastinum in patients receiving radical radiotherapy for NSCLC ( chemotherapy) has the potential to improve treatment outcomes both in terms of disease control and treatment toxicity. One prior study has demonstrated EBUS may detect PET-occult LN metastases in patients being considered for stereotactic radiotherapy for clinical Stage I NSCLC; however, no previous studies have undertaken systematic mediastinal evaluation of patients with locally advanced NSCLC. We hypothesized that systematic mediastinal evaluation with minimally invasive EBUS-TBNA in NSCLC patients being considered for radical radiation therapy may identify disease extent discrepant of that indicated by PET-CT. This may have significant implications for radiation treatment planning and consequently treatment-related outcomes. We conducted a prospective observational study to examine this hypothesis and findings are presented here.