Abstract
Background
With the widespread use of computerized tomography (CT) screening, early-stage small-sized (≤2 cm) non-small cell lung cancer (NSCLC) is increasingly detected. However, the optimal extent of lymph node (LN) dissection for these patients remains controversial. This study aimed to comprehensively investigate the patterns and risk factors of LN metastasis in NSCLC ≤2 cm to guide more precise and individualized surgical management.
Methods
We conducted a retrospective analysis of 1,878 patients with clinical N0 NSCLC ≤2 cm who underwent surgical resection with adequate LN dissection at our institution between December 2009 and November 2019. Univariate and multivariate logistic regression were used to identify risk factors for LN metastasis.
Results
The overall LN metastasis rate was 5.6% (106/1,878). Metastasis rates by lobe were: right upper lobe 4.8% (34/712), right middle lobe 5.3% (10/187), right lower lobe 5.6% (17/305), left upper lobe 6.8% (26/384), and left lower lobe 6.6% (19/290). Upper lobe tumors primarily involved upper mediastinal nodes, while lower lobe tumors mainly metastasized to lower mediastinal nodes. Station 7 metastasis occurred in five upper lobe tumors, all measuring ≥1 cm with pure solid appearance. Multivariate analysis identified tumor size ≥1 cm [odds ratio (OR) =64.41, 95% confidence interval (CI): 9.95–877.52], pure solid radiological appearance (OR =7.88, 95% CI: 4.63–14.37), ≥10 LNs removed (OR =1.64, 95% CI: 1.01–2.76), adenosquamous carcinoma (OR =6.02, 95% CI: 2.27–15.76), and pleural invasion (OR =3.66, 95% CI: 2.17–6.11) as independent risk factors. No LN metastasis occurred in tumors <1 cm or pure ground-glass opacity (GGO) nodules.
Conclusions
Lobe-specific LN dissection is recommended for NSCLC ≤2 cm. For upper lobe tumors ≥1 cm with pure solid appearance, station 7 dissection should be considered. LN dissection may be omitted for pure GGO nodules or tumors ≤1 cm.
Keywords: Non-small cell lung cancer (NSCLC), lymph node metastasis (LN metastasis), lobe-specific dissection, risk factors
Highlight box.
Key findings
• Lymph node (LN) metastasis occurred in 5.6% of 1,878 clinical N0 non-small cell lung cancer (NSCLC) patients with tumors ≤2 cm.
• Upper lobe tumors metastasized predominantly to upper mediastinal stations, while lower lobe tumors involved mainly lower mediastinal nodes.
• Station 7 metastasis was found in five upper lobe tumors, all pure solid and ≥1 cm.
• Independent risk factors included tumor size ≥1 cm, pure solid appearance, ≥10 LNs removed, adenosquamous carcinoma, and pleural invasion.
• No nodal metastasis was detected in tumors <1 cm or pure ground-glass opacity (GGO) nodules.
What is known and what is new?
• Systematic LN dissection may represent overtreatment for small NSCLC, while evidence supporting lobe-specific dissection remains limited.
• This study provides precise lobe-specific metastatic patterns based on a large patient cohort, validates specific criteria for safely omitting LN dissection, and establishes a comprehensive risk stratification system incorporating radiological and pathological factors.
What is the implication, and what should change now?
• Lobe-specific dissection should replace systematic dissection for NSCLC ≤2 cm.
• Clinical guidelines should incorporate tumor size, appearance, and location to optimize the dissection extent.
• Nodal dissection can be omitted for pure GGO or subcentimeter tumors.
Introduction
Lung cancer remains the leading cause of cancer-related mortality worldwide (1). With the widespread use of computed tomography (CT) for lung cancer screening, early-stage small-sized non-small cell lung cancers (NSCLC) are increasingly detected (2). Surgical resection is the standard treatment, and accurate lymph node (LN) evaluation is critical for prognosis and postoperative management (3,4).
Although systematic LN dissection is well established in lung cancer surgery, its necessity in clinical N0 patients with tumors ≤2 cm remains controversial due to the relatively low incidence of LN metastasis (5,6). Moreover, extensive LN dissection is associated with prolonged operative time and increased risk of complications such as chylothorax and nerve injury (7,8). Evidence also suggests that LN dissection may impart immunosuppressive effects, potentially diminishing the efficacy of immunotherapy (9,10). Thus, a key challenge is to minimize the invasiveness of LN dissection without compromising staging accuracy.
A thorough understanding of LN metastasis patterns in NSCLC ≤2 cm is essential for determining the optimal extent of dissection. Previous studies suggest that LN involvement varies by tumor location (11,12), and factors such as tumor size and histology have been identified as potential predictors (5,6,13-15). However, existing evidence regarding LN metastasis patterns and risk factors remains inconsistent (5,13,15). While most studies report a significant association between tumor size and LN metastasis (15), some have found no significant difference between tumors ≤1 cm and those >1–2 cm (6). Similarly, although several studies reported no LN metastasis in tumors ≤1 cm (5), other studies have documented such cases (6,15).
To address these uncertainties, we conducted a retrospective analysis of NSCLC patients with tumors ≤2 cm treated at our center over the past 10 years. The aim was to clarify the patterns and risk factors of LN metastasis in NSCLC ≤2 cm. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2049/rc).
Methods
Patients
Patients with small-sized (≤2 cm) clinical N0 NSCLC who underwent surgical resection with adequate LN evaluation from December 2009 to November 2019 in our center were retrospectively screened. All patients received CT examination before surgery. Positron emission tomography (PET)-CT and contrast-enhanced brain magnetic resonance imaging (MRI) were performed for those with pure solid nodules ≥1 cm. Clinical N0 status was defined as the absence of LN enlargement on CT (short-axis diameter <1 cm) and no abnormal uptake on PET-CT. Adequate LN evaluation was defined as dissection of a minimum of three mediastinal LN stations. Exclusion criteria were: (I) fewer than three mediastinal LN stations examined; (II) clinical N1 or N2 disease; (III) neuroendocrine carcinoma components; (IV) receipt of neoadjuvant therapies; (V) adenocarcinoma in situ; (VI) multiple primary lung cancers. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by The First Affiliated Hospital of Nanjing Medical University Institutional Review Board (No. 2022-SR-760) and waiver of consent was granted due to its retrospective nature.
Data collection
Clinical data included age, sex, smoking history, surgical procedure, and operation time. Tumor characteristics consisted of location, size, consolidation-to-tumor ratio (CTR), radiologic appearance, histologic type, differentiation grade, Ki-67 index, and pleural invasion. For each patient, we documented the number of LN stations dissected and the total LNs removed, along with the number of positive LN stations and metastatic LNs. LN stations were defined according to the International Association for the Study of Lung Cancer (IASLC) map (16). Patients were classified into two groups based on LN metastasis status: the metastasis group and non-metastasis group.
Definitions
LN skip metastasis was defined as metastasis to mediastinal (N2) LNs without N1 involvement. LN evaluation rate was calculated as: (number of cases with LN evaluation/total cases) × 100%. LN metastasis rate was calculated as: (number of cases with LN metastasis/number of cases with LN evaluation) × 100%. LN metastatic degree was calculated as: (total number of metastatic LNs/total number of LNs removed) × 100%.
Statistical analysis
Continuous variables were compared using Student’s t-test or analysis of variance (ANOVA), and categorical variables using the Chi-squared test or Fisher’s exact test. Univariate and multivariate logistic regression analyses were performed to identify factors associated with LN metastasis. Overall survival (OS) was defined as time from surgery to death from any cause, compared using the log-rank test. Analyses were conducted using R (v4.1.2). A P value <0.05 was considered statistically significant.
Results
Cohort characteristics
A total of 1,878 patients were included, with 106 (5.6%) with LN metastasis and 1,772 (94.4%) without metastasis (Table 1). The flowchart is shown in Figure 1. The mean number of LNs removed was 12.8 in the metastasis group vs. 10.4 in the non-metastasis group (P<0.001). Patients with metastasis were older (61.7 vs. 58.5 years, P=0.003) and had a higher prevalence of males (53.8% vs. 32.2%, P<0.001) and smokers (36.8% vs. 11.2%, P<0.001). Tumors in the metastatic group were larger (mean diameter: 1.72 vs. 1.29 cm, P<0.001), had higher CTR (0.96 vs. 0.63, P<0.001), and were more frequently pure solid (84.9% vs. 30.5%, P<0.001). Lobectomy was more common in the metastasis group (91.5% vs. 59.0%, P<0.001). Adenocarcinoma was the predominant type in both groups. However, microinvasive adenocarcinoma accounted for 21.9% of non-metastatic cases but was absent in the metastatic group (P<0.001). Poorly differentiated tumors (54.6% vs. 16.4%, P<0.001) and pleural invasion (28.3% vs. 5.0%, P<0.001) were significantly more common in the metastasis group.
Table 1. Demographic and baseline characteristics of patients in both groups.
| Characteristics | LN non-metastasis group (n=1,772) | LN metastasis group (n=106) | P |
|---|---|---|---|
| Age (years) | 58.5±11.0 | 61.7±8.6 | 0.003 |
| Sex | <0.001 | ||
| Female | 1,202 (67.8) | 49 (46.2) | |
| Male | 570 (32.2) | 57 (53.8) | |
| Smoking history | <0.001 | ||
| Never | 1,573 (88.8) | 67(63.2) | |
| Ever | 199 (11.2) | 39 (36.8) | |
| Lobe location | 0.661 | ||
| Right upper | 678 (38.3) | 34 (32.1) | |
| Right middle | 177 (10.0) | 10 (9.4) | |
| Right lower | 288 (16.3) | 17 (16.0) | |
| Left upper | 358 (20.2) | 26 (24.5) | |
| Left lower | 271 (15.3) | 19 (17.9) | |
| Tumor size (cm) | 1.29±0.47 | 1.72±0.31 | <0.001 |
| CTR | 0.63±0.27 | 0.96±0.11 | <0.001 |
| Radiologic appearance | <0.001 | ||
| Subsolid | 1,232 (69.5) | 16 (15.1) | |
| Solid | 540 (30.5) | 90 (84.9) | |
| Surgical procedure | <0.001 | ||
| Segmentectomy | 668 (37.7) | 4 (3.8) | |
| Wedge resection | 59 (3.3) | 5 (4.7) | |
| Lobectomy | 1,045 (59.0) | 97 (91.5) | |
| Operation time (min) | 146±47 | 160±69 | 0.004 |
| Histologic type | <0.001 | ||
| Adenocarcinoma | 1,706 (96.3) | 94 (88.7) | |
| Squamous carcinoma | 44 (2.5) | 3 (2.8) | |
| Adenosquamous carcinoma | 22 (1.2) | 9 (8.5) | |
| Differentiation degree | <0.001 | ||
| Low | 166 (16.4) | 47 (54.6) | |
| Moderate | 400 (39.4) | 35 (40.7) | |
| High | 448 (44.2) | 4 (4.7) | |
| Pleural invasion | 89 (5.0) | 30 (28.3) | <0.001 |
| Number of LNs removed | 10.4±5.1 | 12.8±5.8 | <0.001 |
Data are presented as number (%) or mean ± SD. CTR, consolidation-to-tumor ratio; LN, lymph node; SD, standard deviation.
Figure 1.
Flow diagram of patient selection. LN, lymph node; N, node; NSCLC, non-small cell lung cancers.
Patterns of LN metastasis
A total of 19,621 LNs were resected, averaging 10.5 per patient. Among these, 374 were pathologically positive, corresponding to an overall metastatic degree of 1.9%. Of the 8,403 N1 LNs, 191 were positive (metastatic degree: 2.3%). Among 11,218 N2 LNs, 183 were positive (metastatic degree: 1.6%). Of the 106 patients with nodal metastasis, 86 (4.6%) had N1 involvement and 65 (3.5%) had N2 involvement. Skip metastasis occurred in 20 patients (1.1%).
The details of LN metastasis rates and degrees for tumors in different lung lobes are shown in Figure 2 and Table 2. The nodal metastasis rates were: right upper 4.8% (34/712), right middle 5.3% (10/187), right lower 5.6% (17/305), left upper 6.8% (26/384), and left lower 6.6% (19/290) (P=0.48). The metastatic degree differed significantly among lobes (P=0.01), with values of 1.8% (138/7,596), 1.9% (33/1,770), 1.3% (44/3,349), 2.4% (89/3,728), and 2.2% (70/3,178), respectively.
Figure 2.
The rates and degrees of LN metastasis for tumors in different lung lobes. (A) LN metastasis rate (%). (B) LN metastatic degree (%). LLL, left lower lobe; LN, lymph node; LUL, left upper lobe; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.
Table 2. LN metastasis patterns for tumors in right lung.
| Characteristics | Total | Station 2R | Station 3 | Station 4R | Station 7 | Station 8 | Station 9 | Station 10 | Station 11 | Station 12 |
|---|---|---|---|---|---|---|---|---|---|---|
| Right upper | ||||||||||
| Cases with LN evaluation† | 712 (100.0) | 375 (52.7) | 16 (2.3) | 390 (54.8) | 679 (95.4) | 18 (2.5) | 243 (34.1) | 651 (91.4) | 412 (57.9) | 324 (45.5) |
| Cases with LN metastasis‡ | 34 (4.8) | 14 (3.7) | 2 (12.5) | 20 (5.1) | 2 (0.3) | 0 (0.0) | 0 (0.0) | 28 (4.3) | 4 (1.0) | 0 (0.0) |
| Total number of metastatic LNs§ | 138 (1.8) | 36 (3.0) | 2 (7.1) | 38 (3.2) | 7 (0.4) | 0 (0.0) | 0 (0.0) | 49 (3.0) | 6 (0.9) | 0 (0.0) |
| Right middle | ||||||||||
| Cases with LN evaluation | 187 (100.0) | 106 (56.7) | 4 (2.1) | 98 (52.4) | 182 (97.3) | 8 (4.3) | 68 (36.4) | 138 (73.8) | 140 (74.9) | 97 (51.9) |
| Cases with LN metastasis | 10 (5.3) | 3 (2.8) | 0 (0.0) | 5 (5.1) | 3 (1.6) | 0 (0.0) | 1 (1.5) | 5 (3.6) | 1 (0.7) | 2 (2.1) |
| Total number of metastatic LNs | 33 (1.9) | 4 (1.4) | 0 (0.0) | 6 (2.2) | 5 (1.3) | 0 (0.0) | 1 (1.0) | 10 (3.8) | 2 (0.7) | 5 (3.2) |
| Right lower | ||||||||||
| Cases with LN evaluation | 305 (100.0) | 153 (50.2) | 12 (3.9) | 154 (50.5) | 301 (98.7) | 17 (5.6) | 156 (51.1) | 209 (68.5) | 242 (79.3) | 171 (56.1) |
| Cases with LN metastasis | 17 (5.6) | 0 (0.0) | 0 (0.0) | 1 (0.6) | 10 (3.3) | 1 (5.9) | 4 (2.6) | 5 (2.4) | 9 (3.7) | 1 (0.6) |
| Total number of metastatic LNs | 44 (1.3) | 0 (0.0) | 0 (0.0) | 2 (0.5) | 13 (1.5) | 1 (4.2) | 5 (2.0) | 6 (1.3) | 15 (3.1) | 2 (0.6) |
Data are presented as number (%). †, LN evaluation rate was calculated as: (number of cases with LN evaluation/total cases) ×100%. ‡, LN metastasis rate was calculated as: (number of cases with LN metastasis/number of cases with LN evaluation) ×100%. §, LN metastatic degree was calculated as: (total number of metastatic LNs/total number of LNs removed) ×100%. LN, lymph node.
Tumors in the right upper lobe exhibited significantly higher metastasis rates in the upper mediastinal (stations 2R, 3, 4R) and hilar (station 10) LNs—3.7%, 12.5%, 5.1%, and 4.3%, respectively (Table 2). Metastasis was rare in the lower mediastinal LN stations, with only two cases (0.3%) in station 7 and none in stations 8 or 9. No obvious differences in nodal involvement were observed for right middle lobe tumors (Table 2). Right lower lobe tumors had higher metastasis rates in lower mediastinal (stations 7, 8, 9) and hilar (stations 10, 11) nodes: 3.3%, 5.9%, 2.6%, 2.4%, and 3.7%, respectively (Table 2). Upper mediastinal involvement was uncommon, with one case (0.6%) in station 4R and none in station 2R. Left upper lobe tumors frequently involved stations 5, 6, 10, and 11 (4.2%, 2.5%, 6.5%, and 2.1%, respectively) (Table 3). Lower mediastinal metastasis was infrequent: three cases (0.8%) in station 7, one (0.4%) in station 9. For left lower lobe tumors, stations 7, 10, and 11 showed relatively higher metastasis rates (3.2%, 3.8%, and 5.3%), whereas stations 5 and 6 were rarely involved (one case each) (Table 3).
Table 3. LN metastasis patterns for tumors in left lung.
| Characteristics | Total | Station 4L | Station 5 | Station 6 | Station 7 | Station 8 | Station 9 | Station 10 | Station 11 | Station 12 |
|---|---|---|---|---|---|---|---|---|---|---|
| Left upper | ||||||||||
| Cases with LN evaluation† | 384 (100.0) | 4 (1.0) | 288 (75.0) | 198 (51.6) | 355 (92.4) | 8 (2.1) | 227 (59.1) | 323 (84.1) | 189 (49.2) | 248 (64.6) |
| Cases with LN metastasis‡ | 26 (6.8) | 0 (0.0) | 12 (4.2) | 5 (2.5) | 3 (0.8) | 0 (0.0) | 1 (0.4) | 21 (6.5) | 4 (2.1) | 3 (1.2) |
| Total number of metastatic LNs§ | 89 (2.4) | 0 (0.0) | 19 (3.5) | 6 (1.7) | 8 (1.2) | 0 (0.0) | 2 (0.5) | 37 (4.5) | 9 (2.6) | 8 (1.5) |
| Left lower | ||||||||||
| Cases with LN evaluation | 290 (100.0) | 0 (0.0) | 217 (74.8) | 113 (39.0) | 281 (96.9) | 10 (3.4) | 220 (75.9) | 260 (89.7) | 209 (72.1) | 159 (54.8) |
| Cases with LN metastasis | 19 (6.6) | 0 (0.0) | 1 (0.5) | 1 (0.9) | 9 (3.2) | 0 (0.0) | 3 (1.4) | 10 (3.8) | 11 (5.3) | 2 (1.3) |
| Total number of metastatic LNs | 70 (2.2) | 0 (0.0) | 1 (0.3) | 1 (0.5) | 22 (3.5) | 0 (0.0) | 4 (1.1) | 15 (1.9) | 21 (5.3) | 6 (1.7) |
Data are presented as number (%). †, LN evaluation rate was calculated as: (number of cases with LN evaluation/total cases) ×100%. ‡, LN metastasis rate was calculated as: (number of cases with LN metastasis/number of cases with LN evaluation) ×100%. §, LN metastatic degree was calculated as: (total number of metastatic LNs/total number of LNs removed) ×100%. LN, lymph node.
Risk factors of LN metastasis
In the univariate regression analysis, male, smoking, tumor size ≥1 cm, pure-solid nodule, ≥10 LNs removed, adenosquamous carcinoma, and pleural invasion were associated with LN metastasis (Table 4). Multivariate regression analysis confirmed tumor size ≥1 cm [odds ratio (OR): 64.41; 95% confidence interval (CI): 9.95–877.52; P<0.001], pure-solid nodule (OR: 7.88; 95% CI: 4.63–14.37; P<0.001), ≥10 LNs removed (OR: 1.64; 95% CI: 1.01–2.76; P=0.045), adenosquamous carcinoma (OR =6.02, 95% CI: 2.27–15.76), and pleural invasion (OR: 3.66; 95% CI: 2.17–6.11; P<0.001) as independent risk factors for LN metastasis.
Table 4. Univariate and multivariate regression analysis of LN metastasis.
| Characteristics | n | LN metastasis, n (%) |
Univariate OR (95% CI) | Multivariate regression analysis | |
|---|---|---|---|---|---|
| OR (95% CI) | P | ||||
| Age, years | |||||
| <60 | 913 | 44 (4.8) | Ref. | ||
| ≥60 | 965 | 62 (6.4) | 1.36 (0.91–2.02) | ||
| Sex | 0.053 | ||||
| Female | 1,251 | 49 (3.9) | Ref. | Ref. | |
| Male | 627 | 57 (9.1) | 2.45 (1.65–3.64) | 1.55 (0.99–2.43) | |
| Smoking history | 0.57 | ||||
| Never | 1,490 | 67 (4.5) | Ref. | Ref. | |
| Ever | 388 | 39 (10.1) | 2.37 (1.57–3.58) | 0.87 (0.54–1.39) | |
| Lobe location | |||||
| Right upper | 712 | 34 (4.8) | Ref. | ||
| Right middle | 187 | 10 (5.3) | 1.13 (0.55–2.32) | ||
| Right lower | 305 | 17 (5.6) | 1.18 (0.65–2.14) | ||
| Left upper | 384 | 26 (6.8) | 1.45 (0.86–2.45) | ||
| Left lower | 290 | 19 (6.6) | 1.40 (0.78–2.49) | ||
| Tumor size, cm | <0.001 | ||||
| <1.0 | 688 | 0 | Ref. | Ref. | |
| 1.0–2.0 | 1,190 | 106 (8.9) | 135.56 (19.67–17,100.92) | 64.41 (9.95–877.52) | |
| Radiologic appearance | <0.001 | ||||
| Subsolid | 1,248 | 16 (1.3) | Ref. | Ref. | |
| Pure solid | 630 | 90 (14.3) | 12.83 (7.47–22.05) | 7.88 (4.63–14.37) | |
| Number of LNs removed | 0.045 | ||||
| <10 | 887 | 26 (2.9) | Ref. | Ref. | |
| ≥10 | 991 | 80 (8.1) | 2.91 (1.85–4.57) | 1.64 (1.01–2.76) | |
| Histologic type | <0.001 | ||||
| Adenocarcinoma | 1,800 | 94 (5.2) | Ref. | Ref. | |
| Squamous carcinoma | 47 | 3 (6.4) | 1.24 (0.38–4.06) | 0.37 (0.09–1.03) | |
| Adenosquamous carcinoma | 31 | 9 (29.0) | 7.42 (3.33–16.57) | 6.02 (2.27–15.76) | |
| Pleural invasion | <0.001 | ||||
| Absent | 1,759 | 76 (4.3) | Ref. | Ref. | |
| Present | 119 | 30 (25.2) | 7.46 (4.65–11.98) | 3.66 (2.17–6.11) | |
CI, confidence interval; LN, lymph node; OR, odds ratio; Ref., reference.
Survival analysis
Patients without LN metastasis demonstrated significantly better OS than those with LN metastasis [hazard ratio (HR) =3.85; 95% CI: 2.84–18.53; P<0.001]. No significant difference in OS was observed between patients with N1 and those with N2 LN involvement (HR =1.41; 95% CI: 0.59–3.47; P=0.44) (Figure 3).
Figure 3.
Survival outcome. (A) The OS of patients with LN metastasis and those without LN metastasis. (B) The OS of patients with N1 and those with N2 LN involvement. HR, hazard ratio; LN, lymph node; N, node; OS, overall survival.
Discussion
With the widespread use of CT for lung cancer screening, early-stage small-sized NSCLC are increasingly detected. Nevertheless, the optimal extent of LN dissection for these tumors remains debated. This study was designed to characterize patterns and risk factors of LN metastasis in NSCLC ≤2 cm to minimize surgical morbidity without compromising oncological outcomes.
Previous studies indicate an LN metastasis incidence of 3.7–19.4% in early-stage NSCLC (13,17-19). In our cohort of 1,878 NSCLC patients, the overall LN metastasis rate was 5.6%, with N1 and N2 involvement rates of 4.6% and 3.5%, respectively, which was consistent with existing literature. We further observed distinct lobe-specific patterns of LN spread. Upper lobe tumors are primarily involved in the upper mediastinal stations, with lower mediastinal involvement being rare. Notably, station 3 had high metastasis rate and degree (12.5% and 7.1%). This may be attributed to selection bias, as station 3 was generally dissected selectively. For right middle lobe tumors, metastasis rates were comparable between upper and lower mediastinal LNs. Lower lobe tumors predominantly involved lower mediastinal LNs, with rare spread to the upper mediastinal or aortic LNs. These distribution patterns are consistent with earlier reports (11,20-22). For instance, Okada et al. (11) observed no lower mediastinal nodal metastases from upper lobe tumors and only one upper mediastinal metastasis from a lower lobe tumor in 141 NSCLC patients with N2 disease.
Based on the patterns of LN metastasis, a lobe-specific dissection strategy has been proposed (7,11). For upper-lobe tumors, subcarinal (inferior mediastinal) dissection is not necessary if the hilar and superior mediastinal LNs are tumor-free (7,11). For lower-lobe tumors, superior mediastinal and aortic LNs dissection can be omitted if the hilar and inferior mediastinal LNs are intact. Previous studies show that lobe-specific dissection achieves oncological outcomes equivalent to systematic nodal dissection in early-stage NSCLC (23-25). The lobe-specific metastasis patterns identified in our study further substantiate the rationale for this approach. Nevertheless, the extent of lobe-specific dissection remains debated, particularly concerning whether subcarinal LNs (station 7) should be dissected for upper lobe tumors (25-27). Our data revealed station 7 metastasis in five cases of upper lobe tumors, all of which were pure solid nodules ≥1 cm in diameter. Therefore, for upper lobe tumors ≥1 cm with a pure solid appearance, dissection of the station 7 LNs is recommended.
Evidence regarding the risk factors for LN metastasis in early NSCLC remains inconsistent (13,17,19,28). Our analysis identified tumor size ≥1 cm, pure solid nodule, ≥10 LNs removed, adenosquamous carcinoma, and pleural invasion as independent risk factors for nodal metastasis in NSCLC ≤2 cm. No LN metastasis was found in tumors <1 cm. A study by Lee et al. (13) that included 593 patients with part-solid clinical stage I lung adenocarcinoma also found no LN metastasis in those with tumors <1 cm. Similarly, Deng et al. reported no LN metastasis in patients with tumors <1 cm in 354 patients with cT1-stage NSCLC (18). However, a study by Ye et al. (14) of 651 patients with clinical stage IA lung adenocarcinoma reported an LN metastasis rate of 5.08% in tumors ≤1 cm, which might be attributed to the higher proportion of pure solid nodules in their cohort. Based on this evidence, we suggest that LN dissection may be omitted for tumors <1 cm, but should be performed for tumors 1–2 cm. Subsolid nodules had significantly lower metastasis rates than pure solid nodules (1.3% vs. 14.3%), with no metastasis observed in pure ground-glass opacity (GGO) nodules. Ye et al. (14) also concluded that LN metastasis was significantly more common in pure solid nodules than in part-solid nodules. Thus, adequate LN evaluation is necessary for pure solid lung cancers, while a conservative approach may be appropriate for subsolid nodules.
The association between the number of LNs removed and prognosis is also debated (29-31). An analysis of 3,269 patients who underwent sublobar resection for early-stage NSCLC demonstrated superior survival in those with more than 4 LNs removed (31). Our retrospective analysis of the SEER database indicated that removing ≥3 LNs during sublobar resection was associated with improved survival (32). Samayoa et al. (29) recommended the removal of at least 10 LNs. In the present study, removing ≥10 LNs was identified as an independent risk factor for LN metastasis in patients with NSCLC ≤2 cm, underscoring the importance of adequate nodal assessment for accurate staging.
This retrospective study delineates patterns and risk factors of LN metastasis in NSCLC with tumors ≤2 cm. However, given the inherent limitations of the retrospective design, the clinical applicability of these patterns in guiding the extent of LN dissection requires validation in large prospective trials.
Conclusions
Lobe-specific LN dissection is a reasonable strategy for patients with NSCLC ≤2 cm. For upper lobe tumors exhibiting a pure solid appearance and measuring ≥1 cm, dissection of the lower mediastinal station 7 LNs is recommended. Tumor size ≥1 cm, pure solid nodules, ≥10 LNs removed, adenosquamous carcinoma, and pleural invasion were significantly associated with LN metastasis. LN dissection may be safely omitted in patients with pure GGO nodules or tumors ≤1 cm.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by The First Affiliated Hospital of Nanjing Medical University Institutional Review Board (No. 2022-SR-760) and waiver of consent was granted due to its retrospective nature.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2049/rc
Funding: This work was supported by the Nanjing Postdoctoral Science Foundation funded project (No. BSHNJ2023004, to X.P.), the China Postdoctoral Science Foundation (No. 2024M751217, to X.P.), the Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2023832, to L.C.), and the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital (No. DL202402, to L.C.).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2049/coif). X.P. reports funding from the Nanjing Postdoctoral Science Foundation funded Project (No. BSHNJ2023004) and the China Postdoctoral Science Foundation (No. 2024M751217). L.C. reports funding from the Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2023832) and the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital (No. DL202402). The other authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2049/dss
References
- 1.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74:12-49. 10.3322/caac.21820 [DOI] [PubMed] [Google Scholar]
- 2.National Lung Screening Trial Research Team ; Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409. 10.1056/NEJMoa1102873 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016;11:39-51. 10.1016/j.jtho.2015.09.009 [DOI] [PubMed] [Google Scholar]
- 4.Burdett S, Pignon JP, Tierney J, et al. Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. Cochrane Database Syst Rev 2015;2015:CD011430. 10.1002/14651858.CD011430 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Yu X, Li Y, Shi C, et al. Risk factors of lymph node metastasis in patients with non-small cell lung cancer ≤ 2 cm in size: A monocentric population-based analysis. Thorac Cancer 2018;9:3-9. 10.1111/1759-7714.12490 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Pani E, Kennedy G, Zheng X, et al. Factors associated with nodal metastasis in 2-centimeter or less non-small cell lung cancer. J Thorac Cardiovasc Surg 2020;159:1088-1096.e1. 10.1016/j.jtcvs.2019.07.089 [DOI] [PubMed] [Google Scholar]
- 7.Okada M, Sakamoto T, Yuki T, et al. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer. Ann Thorac Surg 2006;81:1028-32. 10.1016/j.athoracsur.2005.09.078 [DOI] [PubMed] [Google Scholar]
- 8.Abughararah TZ, Jeong YH, Alabbood F, et al. Lobe-specific lymph node dissection in stage IA non-small-cell lung cancer: a retrospective cohort study. Eur J Cardiothorac Surg 2021;59:783-90. 10.1093/ejcts/ezaa369 [DOI] [PubMed] [Google Scholar]
- 9.Zhao JL, Nie YQ, Yang P, et al. Effect of selective lymph node dissection on immune function in patients with T1 stage non-small cell lung cancer: a randomized controlled trial. Transl Cancer Res 2021;10:2918-31. 10.21037/tcr-21-524 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Fear VS, Forbes CA, Neeve SA, et al. Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used. Cancer Immunol Immunother 2021;70:3249-58. 10.1007/s00262-021-02934-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Okada M, Tsubota N, Yoshimura M, et al. Proposal for reasonable mediastinal lymphadenectomy in bronchogenic carcinomas: role of subcarinal nodes in selective dissection. J Thorac Cardiovasc Surg 1998;116:949-53. 10.1016/S0022-5223(98)70045-5 [DOI] [PubMed] [Google Scholar]
- 12.Miyoshi S, Shien K, Toyooka S, et al. Validity of using lobe-specific regional lymph node stations to assist navigation during lymph node dissection in early stage non-small cell lung cancer patients. Surg Today 2014;44:2028-36. 10.1007/s00595-013-0772-5 [DOI] [PubMed] [Google Scholar]
- 13.Lee SY, Jeon JH, Jung W, et al. Predictive Factors for Lymph Node Metastasis in Clinical Stage I Part-Solid Lung Adenocarcinoma. Ann Thorac Surg 2021;111:456-62. 10.1016/j.athoracsur.2020.05.083 [DOI] [PubMed] [Google Scholar]
- 14.Ye B, Cheng M, Li W, et al. Predictive factors for lymph node metastasis in clinical stage IA lung adenocarcinoma. Ann Thorac Surg 2014;98:217-23. 10.1016/j.athoracsur.2014.03.005 [DOI] [PubMed] [Google Scholar]
- 15.Choi S, Yoon DW, Shin S, et al. Importance of Lymph Node Evaluation in ≤2-cm Pure-Solid Non-Small Cell Lung Cancer. Ann Thorac Surg 2024;117:586-93. 10.1016/j.athoracsur.2022.11.040 [DOI] [PubMed] [Google Scholar]
- 16.Rusch VW, Asamura H, Watanabe H, et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol 2009;4:568-77. [DOI] [PubMed] [Google Scholar]
- 17.Zhang Y, Sun Y, Shen L, et al. Predictive factors of lymph node status in small peripheral non-small cell lung cancers: tumor histology is more reliable. Ann Surg Oncol 2013;20:1949-54. 10.1245/s10434-012-2829-x [DOI] [PubMed] [Google Scholar]
- 18.Deng HY, Zhou J, Wang RL, et al. Surgical Choice for Clinical Stage IA Non-Small Cell Lung Cancer: View From Regional Lymph Node Metastasis. Ann Thorac Surg 2020;109:1079-85. 10.1016/j.athoracsur.2019.10.056 [DOI] [PubMed] [Google Scholar]
- 19.Cho S, Song IH, Yang HC, et al. Predictive factors for node metastasis in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg 2013;96:239-45. 10.1016/j.athoracsur.2013.03.050 [DOI] [PubMed] [Google Scholar]
- 20.Kotoulas CS, Foroulis CN, Kostikas K, et al. Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location. Lung Cancer 2004;44:183-91. 10.1016/j.lungcan.2003.10.012 [DOI] [PubMed] [Google Scholar]
- 21.Watanabe Y, Shimizu J, Tsubota M, et al. Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. Chest 1990;97:1059-65. 10.1378/chest.97.5.1059 [DOI] [PubMed] [Google Scholar]
- 22.Ichinose Y, Kato H, Koike T, et al. Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station. J Thorac Cardiovasc Surg 2001;122:803-8. 10.1067/mtc.2001.116473 [DOI] [PubMed] [Google Scholar]
- 23.Deng HY, Qin CL, Li G, et al. Can lobe-specific lymph node dissection be an alternative to systematic lymph node dissection in treating early-stage non-small cell lung cancer: a comprehensive systematic review and meta-analysis? J Thorac Dis 2018;10:2857-65. 10.21037/jtd.2018.04.137 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Wang Z, Qi Z, Cheng D, et al. Lobe-Specific Node Dissection Can Be a Suitable Alternative to Systematic Lymph Node Dissection in Highly Selective Early-Stage Non-Small-Cell Lung Cancer Patients: A Meta-Analysis. Ann Thorac Cardiovasc Surg 2021;27:143-50. 10.5761/atcs.oa.20-00136 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Hishida T, Miyaoka E, Yokoi K, et al. Lobe-Specific Nodal Dissection for Clinical Stage I and II NSCLC: Japanese Multi-Institutional Retrospective Study Using a Propensity Score Analysis. J Thorac Oncol 2016;11:1529-37. 10.1016/j.jtho.2016.05.014 [DOI] [PubMed] [Google Scholar]
- 26.Adachi H, Sakamaki K, Nishii T, et al. Lobe-Specific Lymph Node Dissection as a Standard Procedure in Surgery for Non-Small Cell Lung Cancer: A Propensity Score Matching Study. J Thorac Oncol 2017;12:85-93. 10.1016/j.jtho.2016.08.127 [DOI] [PubMed] [Google Scholar]
- 27.Ma W, Zhang ZJ, Li Y, et al. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T1a N0 M0 non-small cell lung cancer. J Cancer Res Ther 2013;9:S101-5. 10.4103/0973-1482.119119 [DOI] [PubMed] [Google Scholar]
- 28.Chen B, Xia W, Wang Z, et al. Risk analyses of N2 lymph-node metastases in patients with T1 non-small cell lung cancer: a multi-center real-world observational study in China. J Cancer Res Clin Oncol 2019;145:2771-7. 10.1007/s00432-019-03006-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Samayoa AX, Pezzi TA, Pezzi CM, et al. Rationale for a Minimum Number of Lymph Nodes Removed with Non-Small Cell Lung Cancer Resection: Correlating the Number of Nodes Removed with Survival in 98,970 Patients. Ann Surg Oncol 2016;23:1005-11. 10.1245/s10434-016-5509-4 [DOI] [PubMed] [Google Scholar]
- 30.Ludwig MS, Goodman M, Miller DL, et al. Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer. Chest 2005;128:1545-50. 10.1378/chest.128.3.1545 [DOI] [PubMed] [Google Scholar]
- 31.Cao J, Xu J, He Z, et al. Prognostic impact of lymphadenectomy on outcomes of sublobar resection for stage IA non-small cell lung cancer ≤2 cm. J Thorac Cardiovasc Surg 2018;156:796-805.e4. 10.1016/j.jtcvs.2018.03.122 [DOI] [PubMed] [Google Scholar]
- 32.He Z, Li Z, Xu S, et al. Prognostic Significance of Lymph Node Count Removed at Sublobar Resection in Pathologic Stage IA Non-Small-cell Lung Cancer: A Population-Based Analysis. Clin Lung Cancer 2021;22:e563-73. 10.1016/j.cllc.2020.09.015 [DOI] [PubMed] [Google Scholar]