Study population
The RP-EBUS and combination groups consisted of 506 (83.9%) and 97 (16.1%) participants, respectively. The baseline characteristics of the two study groups are shown in Table 1. The proportion of the male sex and the mean age in the RP-EBUS group were significantly lower compared to the combination group (61.3% vs. 82.5% males, P < 0.001; mean age: 68.1 years vs. 70.4 years, P = 0.021). Compared to the RP-EBUS group, the combination group had larger mean PLL diameters (29.7 mm vs. 36.9 mm, P < 0.001), a greater proportion had a positive bronchus sign (84.2% vs. 93.8%, P = 0.022), and a greater proportion had solid PLLs (86.2% vs. 94.8%, P = 0.039) on thin-section CT.
Table 1
Baseline characteristics.
Variables | RP-EBUS group (n = 506) | Combination group* (n = 97 ) | P-value |
Male sex | 310 (61.3) | 80 (82.5) | < 0.001 |
Age, years | 68.1 (± 10.1) | 70.4 (± 8.9) | 0.021 |
Location of PLL | | | 0.251 |
Right upper lobe | 154 (30.4) | 24 (24.7) | |
Right middle lobe | 34 (6.7) | 11 (11.3) | |
Right lower lobe | 108 (21.3) | 26 (26.8) | |
Left upper lobe | 138 (27.3) | 21 (21.6) | |
Left lower lobe | 72 (14.2) | 15 (15.5) | |
Mean diameter of PLL, mm | 29.7 (± 14.2) | 36.9 (± 17.2) | < 0.001 |
Distance from pleura to PLL, mm | 12.9 (± 14.4) | 12.8 (± 14.9) | 0.922 |
Positive bronchus sign on CT scan | 426 (84.2) | 91 (93.8) | 0.022 |
Character of PLL on CT scan | | | 0.039 |
Solid | 436 (86.2) | 92 (94.8) | |
Mixed | 68 (13.4) | 5 (5.2) | |
Ground-glass opacity | 7 (1.4) | 0 (0) | |
RP-EBUS = radial probe endobronchial ultrasound; PLL = peripheral lung lesion. |
*The combination group included patients who underwent a combined procedure using RP-EBUS and convex probe EBUS. |
Safety profile
The mean procedure time in the combination group was significantly longer than in the RP-EBUS group (29.8 min vs. 19.6 min, P < 0.001). The mean doses of midazolam and fentanyl, administered for conscious sedation, were significantly higher in the combination group compared to the RP-EBUS group (3.5 mg vs. 3.1 mg, P < 0.001, and 58.5 µg vs. 45.8 µg, P < 0.001 for midazolam and fentanyl, respectively). However, there were no differences in the overall complication rates between the RP-EBUS and combination groups (1.4% and 1.0%, respectively; P = 0.766). The most frequent complication was pneumothorax, which occurred in one patient in the combination group and five patients in the RP-EBUS group.
Clinical outcomes of the combination group
In the combination group, subgroups A, B, and C consisted of 47 (48.5%), 32 (33.0%), and 9 (9.3%) participants, respectively (Fig. 2). Table 3 shows the clinical outcomes of the subgroups. In group A (47 patients histologically diagnosed from both the primary tumor and mediastinal LNs), non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were found in 39 and 8 patients, respectively. Among the 39 NSCLC patients in group A, the number of aspirated N1, N2, and N3 LNs were 3, 47, and 5, respectively; clinical stages III and IV were diagnosed in 37 and 2 patients, respectively. Seventeen NSCLC patients underwent thoracoscopic surgery, with or without neo-adjuvant chemotherapy, and there were no false positive or negative results in the 28 LNs examined using CP-EBUS. In addition, all 8 SCLC patients in group A were found to have an extensive stage.
Table 3
Clinical outcomes of groups A, B, and C.
Diagnosis | Group A (n = 47) | Group B (n = 32) | Group C (n = 9) |
Non-small cell lung cancer | 39/47 | 29/32 | 7/9 |
Clinical stage | | | |
I | 0/39 (0) | 8/29 (27.6) | 0/9 (0) |
II | 0/39 (0) | 19/29 (65.5) | 0/9 (0) |
III | 37/39 (94.9) | 0/29 (0) | 7/9 (100.0) |
IV | 2/39 (5.1) | 2/29 (6.9) | 0/9 (0) |
Treatment | | | |
Stereotactic body radiation therapy | 0/39 (0) | 2/29 (6.9) | 0/9 (0) |
Thoracoscopic surgery | 17/39 (43.6) | 19/29 (65.5) | 5/9 (71.4) |
Concurrent chemoradiation therapy | 9/39 (23.1) | 0/29 (0) | 1/9 (14.3) |
Palliative chemotherapy | 8/39 (20.5) | 2/29 (6.9) | 1/9 (14.3) |
Follow-up loss | 5/39 (12.8) | 6/29 (20.7) | 0/9 (0) |
Small-cell lung cancer | 8/47 | 3/32 | 2/9 |
Limited stage | 0/8 (0) | 2/3 (66.7) | 0/2 (0) |
Extensive stage | 8/8 (100) | 1/3 (33.3) | 2/2 (100) |
Among the 29 NSCLC patients in group B, the number of aspirated N1, N2, and N3 LNs were 12, 28, and 5, respectively, and all LNs were negative for malignancy in CP-EBUS-TBNA specimens. Consequently, clinical stages I, II, and IV were diagnosed in 8, 19, and 2 patients (due to unexpected brain metastasis), respectively. In total, 19 patients underwent thoracoscopic surgery with LN dissection, and 4 of the 32 LNs, aspirated using CP-EBUS, were found to be false-negatives. Unexpected N2 LN metastasis was found in the surgical specimen in one patient. In group B, three patients were diagnosed with SCLC, two with limited stage SCLC and one with extensive stage SCLC.
In group C, nine patients were diagnosed using CP-EBUS-TBNA only, and all RP-EBUS-TBB results were found to be false-negative. Among the seven NSCLC patients in group C, the number of aspirated N1, N2, and N3 LNs were two, eight, and one, respectively. All patients were eventually diagnosed with clinical stage III NSCLC. Thoracoscopic surgery was performed in five patients, and there were no false-negative or -positive results in the eight LNs examined using CP-EBUS.
In the combination group, 41 NSCLC patients (54.7%) underwent surgery. Using the surgical specimen as the reference, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CP-EBUS-TBNA were determined to be 86.2%, 100%, 100%, 87.5%, and 93.0%, respectively.