Prognosis of multi-level N2-positive non-small cell lung cancer according to lymph node staging using endobronchial ultrasound-transbronchial biopsy

Abstract

Background: The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) remains controversial, and multidisciplinary team approaches are needed. Downstaging after induction therapy is a good prognostic factor in surgical patients; however, re-evaluation of nodal status before surgery is challenging. The aim of this study was to evaluate the prognosis of patients with multi-level N2 NSCLC who received surgery or chemoradiation therapy (CRT) according to restaging using endobronchial ultrasound-transbronchial aspiration (EBUS-TBNA).

Methods: This was a single center, prospective study that included 16 patients with biopsy-proven multi-level N2 disease on initial EBUS-TBNA that was restaged using EBUS-TBNA after induction therapy. Cases downstaged after rebiopsy were treated surgically. Three-year progression-free survival (PFS) and locoregional PFS were determined using Kaplan-Meier analysis.

Results: Of the 16 patients (median age 58 years, male 63%), eight had persistent N2 disease and eight showed N2 clearance on restaging using EBUS-TBNA. Ten patients underwent surgery, including two patients without N2 clearance. Recurrence and locoregional recurrence occurred in eight and five patients, respectively. The three-year PFS was longer in patients with N2 clearance than in those with N2 persistent disease (57.1% vs. 37.5%). Patients with N2 clearance also had longer three-year locoregional PFS than those with N2 persistent disease (71.4% vs. 62.5%).

Conclusions: EBUS-TBNA could be an effective diagnostic method for restaging in multi-level N2 NSCLC patients after induction CRT. As this was a pilot study, further large-scale randomized studies are needed.

Keywords: Downstaging; endobronchial ultrasound-transbronchial aspiration; multimodality treatment; neoadjuvant therapy; non-small cell lung cancer.

Figure 1

Patient enrollment. CRT, chemoradiation therapy; EBUS, endobronchial ultrasound; TBNA, transbronchial needle biopsy.

Figure 2

Example of a patient with mediastinal nodal downstaging shown by endobronchial ultrasound‐transbronchial needle biopsy (EBUS‐TBNA) restaging after induction therapy. Chest computed tomography (CT) (a) before and (b) after induction chemoradiation therapy (CRT); positron emission tomography (PET)‐CT (c) before and (d) after induction CRT; EBUS (e) before and (f) after induction CRT. Arrows and arrowheads indicate metastatic (a) right hilar and (b) right lower paratracheal lymph nodes, (c) the main lung mass, and (d) right upper paratracheal lymph nodes. (e,f) Arrows indicate the right lower paratracheal lymph nodes.

Figure 3

Example of a patient without mediastinal nodal downstaging shown by endobronchial ultrasound‐transbronchial needle biopsy (EBUS‐TBNA) restaging after induction therapy. Chest computed tomography (CT) (a) before and (b) after induction chemoradiation therapy (CRT); positron emission tomography (PET)‐CT (c) before and (d) after induction CRT; EBUS (e) before and (f) after induction CRT. Arrows indicate metastatic (a,b) left lower paratracheal lymph nodes (c,d) left lower paratracheal lymph nodes, and (e,f) subcarinal lymph nodes.

Figure 4

Comparison of progression‐free survival (PFS) in patients (a) with persistent N2 disease and in those with N2 clearance. N2 persistent, N2 clearing; (b) treated with surgery and definitive chemoradiation therapy (CRT). CRT+operation (CRT+op), definite CRT. Comparison of locoregional PFS in patients (c) with persistent N2 disease and in those with N2 clearance. N2 persistent, N2 clearing; and (d) treated with surgery and definitive CRT. CRT+op, definite CRT.