Among 5613 cN0–1 NSCLC patients, 394 cases (7.0%) with pN2 were enrolled, and 213 had right NSCLC while the other 181 had left NSCLC. The distributions of mediastinal lymph node metastasis in right and left sides were listed in Table
1 and Table
2, respectively.
Table 1Mediastinal lymph node metastasis in right-sided NSCLC
Upper zone | 74/78 (94.9%) | 20/35 (57.1%) | 55/100 (55.0%) | < 0.001 |
2R | 34/78 (43.6%) | 13/35 (37.1%) | 14/100 (14.0%) | < 0.001 |
3 | 12/29 (41.4%) | 5/14 (35.7%) | 15/43 (34.9%) | 0.848 |
4R | 63/78 (80.8%) | 18/35 (51.4%) | 43/100 (43.0%) | < 0.001 |
Subcarinal zone |
7 | 17/78 (21.8%) | 29/35 (82.9%) | 86/100 (86.0%) | < 0.001 |
Lower zone | 2/78 (2.6%) | 1/35 (2.9%) | 13/100 (13.0%) | 0.017 |
8 | 1/78 (1.3%) | 0/35 (0) | 9/100 (9.0%) | 0.019 |
9 | 2/78 (2.6%) | 1/35 (2.9%) | 5/100 (5.0%) | 0.666 |
Negative LSLNS | 4/78 (5.1%) | / | 11/100 (11.0%) | 0.162 |
Table 2Mediastinal lymph node metastasis in left-sided NSCLC
Upper zone | 84/97 (86.6%) | 30/84 (35.7%) | < 0.001 |
4 L | 14/29 (48.3%) | 7/22 (31.8%) | 0.237 |
5 | 71/97 (73.2%) | 24/84 (28.6%) | < 0.001 |
6 | 27/97 (27.8%) | 10/84 (11.9%) | 0.008 |
Subcarinal zone |
7 | 25/97 (25.8%) | 57/84 (67.9%) | < 0.001 |
Lower zone | 4/97 (4.1%) | 32/84 (38.1%) | < 0.001 |
8 | 1/97 (1.0%) | 12/84 (14.3%) | 0.001 |
9 | 4/97 (4.1%) | 27/84 (32.1%) | < 0.001 |
Negative LSLNS | 12/97 (12.4%) | 12/84 (14.3%) | 0.705 |
Right upper lobe (RUL): lymph nodes in upper zone were involved much more often in the RUL compared with the other two lobes (94.9% vs. 57.1% vs. 55.0%, P < 0.001). Station 4R (80.8%) had the highest proportion to be involved, followed by station 2R (43.6%) and station 3 (41.4%). Station 7 involvement (21.8%) was also occurred with a relatively high proportion. Lymph nodes in station 8 (1.3%) and station 9 (2.6%) were less likely to be involved than other stations.
Right middle lobe (RML): the highest proportion of metastasis was observed in subcarinal zone, station 7 (82.9%). The involvement of upper zone was common as well, with 51.4% in station 4R, 35.7% in station 3 and 37.1% in station 2R. Only 1 patient (2.9%) had positive lymph nodes in the lower zone.
Right lower lobe (RLL): station 7 (86.0%) was also the most common site to be involved in the RLL, follow by station 4R (43.0%). The involvement of station 2R (14.0%) and station 3 (34.9%) was not rare. The metastasis of RLL to the lower zone was more often than the RUL and RML (13.0% vs. 2.6% vs. 2.9%, P = 0.017).
It was notable that 4 patients (5.1%) with RUL tumors had negative LSLNS and 11 patients (11.0%) with RLL tumors had negative LSLNS.
Left upper lobe (LUL): station 5 (73.2%) was the most common site to be involved, followed by station 4 L (48.3%) and 6 (27.8%). The involvement of station 7 (25.8%) was also not rare. As was expected, metastases in the lower zone lymph nodes occupied small percentage, with only 4.1%.
Left lower lobe (LLL): the highest proportion of metastasis was observed in station 7 (67.9%), far more common than the LUL (P < 0.001). It should be noted that the proportion of the upper zone lymph nodes involvement (35.7%) was not far less than that of the lower zone involvement (38.1%).
It should be emphasized that there were 12.4 and 14.3% pN2 patients having negative LSLNS in the LUL and LLL, respectively.
Characteristics of patients with NLSLNM and LSLNM
All enrolled patients except those with RML tumors were divided into the NLSLNM group and LSLNM group on the basis of the lymphatic metastasis pattern, with 129 in NLSLNM group and 230 in LSLNM group. Clinical and pathological characteristics of two groups were shown in Table
3 and Table
4.
Table 3Clinical characteristics of patients with NLSLNM and LSLNM
Sex | | | 0.149 |
Male | 61 (47.3%) | 127 (55.2%) | |
Female | 68 (52.7%) | 103 (44.8%) | |
Age, years | | | 0.176 |
Median (range) | 61 (26–83) | 60.5 (27–80) | |
Smoking history | 42 (32.6%) | 115 (50.0%) | 0.001 |
Hypertension | 21 (16.3%) | 66 (28.7%) | 0.008 |
Diabetes | 8 (6.2%) | 14 (6.1%) | 0.965 |
Other pulmonary diseases | 5 (3.9%) | 5 (2.2%) | 0.544 |
Other malignant tumors within 5 years | 0 (0) | 4 (1.7%) | 0.326 |
CEA level | | | 0.004 |
>5 ng/ml | 65 (50.4%) | 80 (34.8%) | |
≤5 ng/ml | 64 (49.6%) | 150 (65.2%) | |
Tumor location | | | < 0.001 |
RUL | 19 (14.7%) | 59 (25.7%) | |
RLL | 54 (41.9%) | 46 (20.0%) | |
LUL | 26 (20.2%) | 71 (30.9%) | |
LLL | 30 (23.3%) | 54 (23.5%) | |
CT characteristics | | | 0.404 |
GGO | 1 (0.8%) | 1 (0.4%) | |
Partially solid | 4 (3.1%) | 14 (6.1%) | |
Solid | 124 (96.1%) | 215 (93.5%) | |
Clinical T stage | | | 0.493 |
T1a | 2 (1.6%) | 4 (1.7%) | |
T1b | 19 (14.7%) | 49 (21.3%) | |
T1c | 47 (36.4%) | 70 (30.4%) | |
T2a | 27 (20.9%) | 56 (24.3%) | |
T2b | 20 (15.5%) | 27 (11.7%) | |
T3 | 13 (10.1%) | 19 (8.3%) | |
T4 | 1 (0.8%) | 5 (2.2%) | |
Clinical N stage | | | 0.647 |
N0 | 118 (91.5%) | 207 (90.0%) | |
N1 | 11 (8.5%) | 23 (10.0%) | |
Surgical approach | | | 0.052 |
Thoracotomy | 71 (55.0%) | 102 (44.3%) | |
VATS | 58 (45.0%) | 128 (55.7%) | |
Surgical resection | | | 0.345 |
Segmentectomy | 2 (1.6%) | 6 (2.6%) | |
Lobectomy | 120 (93.0%) | 207 (90.0%) | |
Sleeve lobectomy | 2 (1.6%) | 11 (4.8%) | |
Pneumonectomy | 5 (3.9%) | 6 (2.6%) | |
Table 4Pathological characteristics of patients with NLSLNM and LSLNM
Anatomical type | | | 0.168 |
Central | 31 (24.0%) | 71 (30.9%) | |
Peripheral | 98 (76.0%) | 159 (69.1%) | |
Histology | | | 0.022 |
Adenocarcinoma | 103 (79.8%) | 161 (70.0%) | |
SCC | 14 (10.9%) | 52 (22.6%) | |
Others | 12 (9.3%) | 17 (7.4%) | |
Cell differentiation | | | 0.480 |
Well-moderate | 3 (2.3%) | 2 (0.9%) | |
Moderate | 25 (19.4%) | 56 (24.3%) | |
Moderate-poor | 62 (48.1%) | 111 (48.3%) | |
Poor | 33 (25.6%) | 52 (22.6%) | |
NAa | 6 (4.7%) | 9 (3.9%) | |
Pathological T stage | | | 0.886 |
T1a | 1 (0.8%) | 2 (0.9%) | |
T1b | 17 (13.2%) | 31 (13.5%) | |
T1c | 24 (18.6%) | 33 (14.5%) | |
T2a | 54 (41.9%) | 112 (48.7%) | |
T2b | 17 (13.2%) | 24 (10.4%) | |
T3 | 12 (9.3%) | 21 (9.1%) | |
T4 | 4 (3.1%) | 7 (3.0%) | |
Pathological TNM stage | | | 0.853 |
IIIA | 113 (87.6%) | 203 (88.3%) | |
IIIB | 16 (12.4%) | 27 (11.7%) | |
Tumor sizeb, cm | | | 0.830 |
Median (range) | 3.0 (0.8–8.0) | 3.0 (0.9–10.0) | |
Visceral pleural invasion | 51 (39.5%) | 73 (31.7%) | 0.136 |
Lymphovascular invasion | 30 (23.3%) | 44 (19.1%) | 0.354 |
Skip N2 metastasis | 25 (19.4%) | 65 (28.3%) | 0.062 |
N1 involvement |
10 | 51 (39.5%) | 61 (26.5%) | 0.011 |
11 | 47 (36.4%) | 48 (20.9%) | 0.001 |
12 | 83 (64.3%) | 124 (53.9%) | 0.055 |
There were no statistical differences in sex and age between two groups. In contrast, more patients in LSLNM group had smoking history (50.0% vs. 32.6%, P = 0.001) and hypertension (28.7% vs. 16.3%, P = 0.008) than those in NLSLNM group. Abnormally elevated carcinoembryonic antigen (CEA) level (>5 ng/ml) was detected in more patients in NLSLNM group than LSLNM group (50.4% vs. 34.8%, P = 0.004). The NLSLNM group significantly tended to have RLL tumors while the LSLNM group was more likely to have upper lobe tumors (P < 0.001). The proportion of solid tumors presenting on CT scan was comparable at approximately 95% in both groups. It was worth mentioning that there was one patient in both groups presenting ground-glass opacity (GGO) on CT scan. Clinical T stage and N stage were also similar in two groups.
There were no significant differences in pathological characteristics, except for histology and N1 involvement. Adenocarcinoma was observed in greater percentage of patients in NLSLNM group while squamous cell carcinoma was detected more often in LSLNM group (P = 0.022). Station 10 and 11 lymph nodes were less likely to be involved in LSLNM group compared with those in NLSLNM group (26.5% vs. 39.5%, P = 0.011 and 20.9% vs. 36.4%, P = 0.001, respectively).
Factors predicting NLSLNM
The univariate analysis showed that smoking history, hypertension, CEA level, tumor location, histology, stations 10 and 11 involvement were statistically significant factors influencing the lymphatic metastasis pattern. Multivariate analysis was further performed for these factors (Table
5). The results indicated that hypertension (
P = 0.025), CEA level (
P = 0.034), tumor location (
P = 0.022) and station 11 involvement (
P = 0.030) were statistically associated with NLSLNM. High CEA level (OR = 1.684, 95% CI = 1.040–2.725), RLL tumors (OR = 2.111, 95% CI = 1.116–3.992) and station 11 involvement (OR = 1.774, 95% CI = 1.056–2.980) were independent risk factors for NLSLNM, while hypertension (OR = 0.512, 95% CI = 0.286–0.918) was a protective factor for NLSLNM.
Table 5Independent predictive factors of non-lobe specific lymph node metastasis
Hypertension | 0.025 | 0.512 | 0.286–0.918 |
Smoking history | 0.077 | 0.617 | 0.361–1.053 |
CEA level | 0.034 | 1.684 | 1.040–2.725 |
Tumor location |
RUL | 0.165 | 0.598 | 0.289–1.236 |
RLL | 0.022 | 2.111 | 1.116–3.992 |
LUL | 0.335 | 0.717 | 0.364–1.411 |
LLL | / | 1 | / |
Histology |
Adenocarcinoma | / | 1 | / |
SCC | 0.487 | 0.759 | 0.348–1.654 |
Others | 0.733 | 1.162 | 0.491–2.749 |
N1 involvement |
10 | 0.152 | 1.446 | 0.873–2.396 |
11 | 0.030 | 1.774 | 1.056–2.980 |