Abstract
Objective
Besides the discussion on parenchymal margin, data on the extent of lymph node (LN) dissection are scarce, especially in segmentectomy. This study aimed to investigate the extent of LN dissection and detection of occult disease in segmentectomy compared with lobar resection.
Methods
We performed a single-institution, retrospective analysis for patients who underwent segmentectomy or lobectomy for clinical T1N0M0 (≤3 cm) NSCLC from 2012 to 2022. The extent of LN dissection and the rate of detection of occult LN disease were compared. N1 nodes were further classified as collected as a specimen during the operation (N1 dissection) and the nodes retrieved from lung specimens by pathologists (N1 lung specimen).
Results
During the study period, 957 lobectomies and 402 segmentectomies were performed for clinical T1N0M0 NSCLC. The median number of sampled LNs was significantly higher in the lobectomy group (18 versus 12; p < 0.001). This tendency was similar across all node groups, including N2 nodes (7 versus 5), N1 dissection nodes (6 versus 4), and most significantly N1 lung specimen nodes (4 versus 0; all p < 0.001) There was a significant difference in N1 occult nodes (13.3% versus 3.7%; p < 0.001), whereas the difference was not significant in N2 occult nodes (5.5% versus 3.2%; p = 0.074).
Conclusions
Segmentectomy was associated with less LN sampling, which translated into lower detection of occult nodal metastasis in N1 LNs. Although standardized pathologic dissection could potentially improve detection, there is likely an inevitable inferiority in LN sampling with segmentectomy.
Keywords: NSCLC, Segmentectomy, Lymph node dissection
Introduction
Over the previous few years, two large randomized controlled trials from Japan and the United States have reported the noninferiority of segmentectomy to lobectomy for survival in early-stage NSCLC.1,2 Sublobar resection, including segmentectomy, is a new standard for early NSCLC, and its application is expected to expand. Although this paradigm change will deliver more opportunities for lung parenchymal preservation, it raises new clinical challenges, such as occult nodal metastasis diagnosed on final pathology after sublobar resection. Occult nodal disease in stage I NSCLC is not rare, and the prevalence was reported at 14.3% for thoracotomy and 11.6% for video-assisted thoracic surgery (VATS) from the Society of Thoracic Surgeons database.3 Besides the discussion on parenchymal resection, data on the extent of lymph node (LN) dissection are scarce, especially in segmentectomy. This study aimed to investigate the extent of LN dissection and detection of occult disease in segmentectomy compared with lobar resection to detect the area of improvement.
Patients and Methods
We performed a single-center retrospective analysis of patients who underwent segmentectomy or lobectomy for clinical T1N0M0 (≤3 cm) NSCLC at the University of Pittsburgh Medical Center from January 1, 2012, to December 31, 2022. The patients with pathologic nodal disease were detected, and their clinicopathologic background was compared with the patients without occult nodal disease. The extent of nodal harvest and occult nodal detection rate were compared between lobectomy and segmentectomy. Of note, survival analysis with occult nodal disease is not the primary focus of this article, which was analyzed in a separate article currently under review.
In addition to the occult nodal detection rate, the extent of LN dissection was compared between lobectomy and segmentectomy. LN sampling was analyzed by total count and station at each level (N1 versus N2). N1 nodes were further classified as nodes collected from intraoperative dissection (N1 dissection) and nodes retrieved from lung specimens dissected by pathologists (N1 lung specimen). Although our division encourages meticulous LN dissection, there was no mandated protocol for uniform lymphadenectomy across the study period except for the evolving guidelines. There was no standardized protocol for sampling stations #5 and #6, and this variability should be acknowledged as a limitation of our analysis. Following the most recent American College of Surgeons (ACS) Commission on Cancer and National Comprehensive Cancer Network guidelines, implemented in 2021, a guideline-concordant LN dissection was defined as a minimum of one N1 station and three N2 stations sampled or a complete LN dissection. Overall survival was compared between lobectomy and segmentectomy for the entire cohort.
Patients were staged according to the eighth edition of the American Joint Committee on Cancer staging system. All patients underwent preoperative imaging (computerized tomography [CT] scan and positron emission tomography/CT). Clinical stage was obtained with a combination of preoperative imaging and staging procedures. All patients with suspected nodal disease who met the criteria of American College of Chest Physicians guidelines4 were considered for preoperative nodal staging in the form of endobronchial ultrasound fine-needle aspiration or mediastinoscopy before resection. All patients had tissue diagnoses of malignancy before proceeding with resection, preoperatively or intraoperatively. Patients undergoing bilobectomy, concurrent anatomical resections, or pneumonectomy were excluded. In addition, patients who received neoadjuvant treatment and exhibited coexisting small cell carcinoma histology, synchronous tumors, positive margins, or inadequate preresection nodal staging were excluded. Anatomical segmentectomy was accomplished by the removal of one or more pulmonary segments with the goal of an R0 resection. This was accomplished by the individual isolation and division of at least two segmental bronchial and vascular structures. Approval for this study was obtained from the institutional review board of the University of Pittsburgh (STUDY20050076), which waived the requirement for individual patient consent.
Statistical Analysis
Distributions of continuous variables (age, tumor size, LNs harvested) were analyzed using Wilcoxon or t tests, as appropriate, whereas Fisher’s exact tests were used to compare frequencies of categorical measures (sex, histology, stage). Survival time was analyzed using the Kaplan-Meier method with a log-rank test. Logistic regression models were conducted to identify factors associated with occult nodal detection. All statistical analyses were performed using the IBM SPSS software for Mac version 29 (SPSS, Inc., Chicago, IL).
Results
During the study period, 957 lobectomies and 402 segmentectomies were performed for clinical T1N0M0 NSCLC. Occult LN metastasis was identified in 140 patients after lobectomy versus 21 patients after segmentectomy (14.6% versus 5.2%; p < 0.001). Among them, 32 cases with lobectomy (22.9%) and two cases with segmentectomy (9.5%) were found node positive with intraoperative frozen section. Of note, eight patients in the lobectomy group were converted from originally planned segmentectomy owing to node-positive status with frozen section. The overall survival was similar between lobectomy and segmentectomy (median, 106.3 months versus 103.6; p = 0.576) (Supplementary Fig. 1A). The patients with occult N1 disease or N2 disease had significantly shorter median overall survival than the patients without occult nodal disease (median, 76.7 and 49.1 versus 107.2 months; p < 0.001 for both) (Supplementary Fig. 1B), whereas there is no statistically significant difference between N1 and N2 diseases (p = 0.398). In the patients without occult nodal disease (pN0), the overall survival was similar between lobectomy and segmentectomy (median, 107.2 versus 106.2 months; p = 0.924) (Supplementary Fig. 1C). Adjuvant chemotherapy was delivered in 140 patients (87.0% of pN+ patients). An ad hoc analysis in this population found significantly longer overall survival than the patients who did not receive adjuvant chemotherapy (median, 84.7 versus 27.9 months; p = 0.001) (Supplementary Fig. 1D).
The demographic and clinical variable distributions between the segmentectomy and lobectomy groups are presented in Table 1. The patient’s age and smoking history were similar across the groups. Most cases were performed by a minimally invasive approach (>90% in both groups), with VATS or robot-assisted thoracic surgery (RATS). The lobectomy group had larger tumors (median, 2.0 versus 1.6 cm; p < 0.001) and higher maximum standardized uptake value of the primary tumors (median, 3.8 versus 2.2; p < 0.001). The number of sampled node stations was higher in the lobectomy group (median, 5 versus 4; p < 0.001). Likewise, the median number of sampled LNs was significantly higher in the lobectomy group (18 versus 12; p < 0.001). This tendency was similar across all node groups, including N2 nodes (7 versus 5), N1 dissection nodes (6 versus 4), and most significantly N1 lung specimen nodes (4 versus 0; all p < 0.001) (Fig. 1). As a result, guideline-concordant dissection was achieved more frequently in the lobectomy group (51.0% versus 44.0%; p = 0.020), whereas guideline-concordant dissection was not associated with overall survival difference (median, 100.0 versus 106.3 months; p = 0.737) (Supplementary Fig. 2). N1 LN sampling frequencies at stations #10, #11, and #12 are presented in Supplementary Figure 3. Sampling rates are higher in lobectomy than segmentectomy at stations #10 (71.6% versus 61.9%) and #11 (88.6% versus 80.3%), both significant (p < 0.001). Station #12 shows similar sampling rates (28.0% versus 29.9%) with no significant difference (p = 0.492). The positive rate for each station was higher in lobectomy for #10 (4.2% versus 0.5%; p < 0.001), #11 (4.4% versus 1.7%; p = 0.016), and #12 (2.6% versus 0.2%; p = 0.002).
Table 1.
Demographics and Patients’ Characteristics of Each Group
| Variables | Segmentectomy |
Lobectomy |
p Value | |
|---|---|---|---|---|
| No. of patients (%) | No. of patients (%) | |||
| Total number | 402 | 957 | ||
| Sex | Male | 150 (37.3) | 409 (42.7) | 0.070 |
| Female | 252 (62.7) | 548 (57.3) | ||
| Age, y, median [IQR] | 68 [63, 74] | 68 [61, 74] | 0.068 | |
| Smoking history | Never | 40 (10.0) | 120 (12.5) | 0.198 |
| Past smoker | 256 (63.7) | 563 (58.8) | ||
| Current smoker | 106 (26.4) | 274 (28.6) | ||
| Smoking, pack-years, median [IQR] | 40 [20–50] | 38 [19–50] | 0.089 | |
| Laterality | Right | 179 (44.5) | 622 (65.0) | < 0.001 |
| Left | 223 (55.5) | 335 (35.0) | ||
| Lobe | Right upper | 92 (22.9) | 353 (36.9) | < 0.001 |
| Right middle | 2 (0.5) | 84 (8.8) | ||
| Right lower | 85 (21.1) | 185 (19.3) | ||
| Left upper | 153 (38.1) | 202 (21.1) | ||
| Left lower | 70 (17.4) | 133 (13.9) | ||
| Approach | Open | 21 (5.2) | 84 (8.8) | 0.017 |
| VATS | 287 (71.4) | 615 (64.3) | ||
| RATS | 94 (23.4) | 258 (27.0) | ||
| Histology | Adenocarcinoma | 277 (69.3) | 663 (69.4) | 0.164 |
| Squamous cell carcinoma | 94 (23.5) | 191 (20.0) | ||
| Large cell carcinoma | 8 (2.0) | 38 (4.0) | ||
| Adenosquamous cell carcinoma | 8 (2.0) | 18 (1.9) | ||
| Others | 13 (3.3) | 46 (4.8) | ||
| Clinical tumor size, cm, median [IQR] | 1.6 [1.2, 2.0] | 2.0 [1.5, 2.5] | < 0.001 | |
| Clinical T stage | cT1a | 59 (14.5) | 56 (5.9) | < 0.001 |
| cT1b | 243 (60.4) | 477 (49.8) | ||
| cT1c | 100 (24.9) | 424 (44.3) | ||
| SUVmax, median, [IQR] | 2.2 [1.2–4.4] | 3.8 [2.0–7.0] | < 0.001 | |
| No. lymph node harvest | Total, median [IQR] | 12 [7–17] | 18 [13–24] | < 0.001 |
| N1 dissection, median [IQR] | 4 [1–7] | 6 [3–9] | < 0.001 | |
| N1 lung, median [IQR] | 0 [0–2] | 4 [2–7] | < 0.001 | |
| N2, median [IQR] | 5 [3–9] | 7 [4–12] | < 0.001 | |
| No. lymph node station harvest | Total, median [IQR] | 4 [3–5] | 5 [4–5] | < 0.001 |
| N1, median [IQR] | 2 [1–2] | 2 [1–2] | < 0.001 | |
| N2, median [IQR] | 2 [2–3] | 3 [2–3] | 0.005 | |
| Pathologic N stage | pN0 | 381 (94.8) | 817 (85.4) | < 0.001 |
| pN1 | 8 (2.0) | 88 (9.2) | ||
| pN2 | 13 (3.2) | 52 (5.4) | ||
| Guideline-concordant dissection | 177 (44.0) | 488 (51.0) | 0.020 | |
Pearson’s chi-squared test for categorical variables and Wilcoxon rank sum tests for continuous variables.
IQR, interquartile range; RATS, robot-assisted thoracic surgery; SUVmax, maximum standardized uptake value; VATS, video-assisted thoracic surgery.
Figure 1.
Box-and-whisker plot illustrating the distribution of the count of harvested lymph nodes for each lymph node group (red, N2 nodes; blue, N1 dissection nodes; light blue, N1 lung specimen nodes). The boxes represent the interquartile range from the 25th to 75th percentile, with the horizontal line inside the box indicating the median value. The whiskers extend to the smallest and largest observations within 1.5 times the interquartile range, and outliers beyond this range are presented as individual points.
In the pathologic stage, 88 patients in the lobectomy group (9.2%) and eight patients in the segmentectomy group (2.0%) were staged pN1. In comparison, 52 patients in the lobectomy group (5.4%) and 13 patients in the segmentectomy group (3.2%) were staged pN2. Among pN2 patients, positive N1 nodes were not detected in 13 patients (25% of pN2) in the lobectomy group and six patients (46% of pN2) in the segmentectomy group (p = 0.190). The frequency of occult nodal detection rate by each tumor size is presented in Figure 2. In the lobectomy group, occult nodal disease was identified in 16.1% (9 of 47; N1 12.5% and N2 3.6%) even in clinical T1 tumors (≤1 cm). The segmentectomy group consistently showed lower occult node detection rates, with none found in clinical T1a tumors (0 of 59).
Figure 2.
Frequency of occult nodal disease in each tumor size category. Red, pN2; blue, pN1. The segmentectomy group showed no occult nodal disease in clinical T1a tumors (0 of 59). Across all T1 subgroups, lobectomy consistently detected more occult nodes than segmentectomy.
The details of the detection rate for each LN group are presented in Figure 3. There was a significant difference in N1 occult node detection between lobectomy and segmentectomy (13.3% versus 3.7%; p < 0.001), whereas the difference was not significant in N2 occult nodes (5.5% versus 3.2%; p = 0.074) (Fig. 3A). In further detail for N1 LN groups, the segmentectomy group has lower detection rates in both N1 dissection nodes (8.4% versus 2.5%; p < 0.001) and N1 lung specimen nodes (7.6% versus 1.7%; p < 0.001). Of note, when accounting for eight cases with intraoperative conversion to lobectomy as originally planned segmentectomy, the tendency is unchanged for both N1 (12.8% versus 5.1%; p < 0.001) and N2 (4.8% versus 4.9%; p = 1.000) (Fig. 3B).
Figure 3.
Occult nodal detection rate in each lymph node group. Red, N2 nodes; blue, N1 dissection nodes; light blue, N1 lung specimen nodes. (A) Lobectomy versus segmentectomy, analysis based on what was actually performed. (B) Analysis based on the original intent of surgery, accounting for eight intraoperative conversions to lobectomy as segmentectomy.
Variables associated with occult nodal disease detection are presented in Table 2. Although patient and tumor characteristics likely reflect the true incidence of occult LN metastasis, the surgical approach and extent of lymphadenectomy primarily influence the detection rate. To account for baseline differences, logistic regression models were used to identify factors associated with occult nodal detection. Given that VATS lobectomy is the most widely adopted approach for early-stage NSCLC, we selected it as the reference standard. The model identified segmentectomy compared with lobectomy (odds ratio [OR] = 0.27; 95% confidence interval [CI]: 0.17–0.45; p < 0.001), open approach compared with VATS (OR = 3.03; 95% CI: 1.79–5.14; p < 0.001), RATS approach compared with VATS (OR = 2.02; 95% CI: 1.33–3.07; p = 0.001), the number of sampled stations (OR = 1.16; 95% CI: 1.02–1.33; p = 0.024), and maximum standardized uptake value of the primary tumor (OR = 1.05; 95% CI: 1.01–1.09; p = 0.009) (Fig. 4). Age, the number of sampled nodes, guideline-concordant dissection, and clinical tumor size were not independent predictors for occult nodal detection in this model.
Table 2.
Variables Associated with Occult Node Detection
| Variables | No Occult Disease (n = 1198) | Occult Disease (n = 161) | p Value | |
|---|---|---|---|---|
| pN stage | pN1 | - | 96 | |
| pN2 | - | 65 | ||
| Operation | Lobectomy (%) | 817 (85.4) | 140 (14.6) | < 0.001 |
| Segmentectomy (%) | 381 (94.8) | 21 (5.2) | ||
| Approach | Open (including conversion) (%) | 76 (72.4) | 29 (27.6) | < 0.001 |
| VATS (%) | 818 (90.7) | 84 (9.3) | ||
| RATS (%) | 304 (86.4) | 48 (13.6) | ||
| Smoking | Never (%) | 140 (87.5) | 20 (12.5) | 0.531 |
| Past (%) | 717 (89.7) | 102 (10.3) | ||
| Current (%) | 341 (90.9) | 39 (9.1) | ||
| cT stage | cT1 (%) | 106 (92.2) | 9 (7.8) | 0.007 |
| cT2 (%) | 648 (90.0) | 72 (10.0) | ||
| cT3 (%) | 444 (84.7) | 80 (15.3) | ||
| Age, y, median [IQR] | 68 [62–74] | 68 [61–73] | 0.399 | |
| SUVmax, median [IQR] | 2.9 [1.6–5.8] | 4.9 [2.8–7.6] | < 0.001 | |
| Clinical tumor size (cm), median [IQR] | 1.8 [1.4–2.3] | 2.0 [1.6–2.5] | 0.001 | |
| Sampled node | Total, median [IQR] | 16 [11–22] | 19 [12–26] | < 0.001 |
| Sampled station, median [IQR] | 4 [3.5–5] | 5 [4–5] | 0.081 | |
| Guideline-concordant dissection | 586 (48.9) | 79 (49.1) | 1.000 | |
IQR, interquartile range; RATS, robot-assisted thoracic surgery; SUVmax, maximum standardized uptake value; VATS, video-assisted thoracic surgery.
Figure 4.
Forest plot illustrating the ORs for factors associated with occult nodal detection. Error bars represent the 95% CIs for each OR. A dashed red line at OR = 1 indicates no effect. CI, confidence interval; OR, odds ratio; RATS, robot-assisted thoracic surgery; SUVmax, maximum standardized uptake value; VATS, video-assisted thoracic surgery.
Comment
NSCLC with occult nodal metastasis presents a challenging clinical situation, both diagnostic and therapeutic. Even with the relatively high sensitivity of positron emission tomography/CT, 81.3% in a meta-analysis,5 occult nodal disease cannot be totally excluded, especially for N1 disease that is difficult to evaluate even with invasive modalities (mediastinoscopy and endoscopic bronchial ultrasound). In the subset analysis of nonrandomized patients in the Cancer and Leukemia Group B 140503 trial, the exclusion rate with nodal upstaging was 6.4% in the setting of mandatory LN assessment, even after the strict preoperative workup.6
One important difference found between segmentectomy and lobectomy is the extent of LN dissection. In a National Cancer Database study, the extent of LNs harvested was significantly different between lobectomy and segmentectomy (mean, 10.8 versus 8.5; p < 0.001), which was associated with an increased upstaging rate (N1, 6.7% versus 2.5%; N2, 3.9% versus 2.4%; both p < 0.001).7 More recently, another National Cancer Database analysis repeatedly found the same trends of LN examination with lobectomy (mean, 12.0) and segmentectomy (9.1); wedge resection showed a further decrease (6.3). This observed difference in LN harvest resulted in different upstaging rates (lobectomy, 7.7%; segmentectomy, 3.8%; wedge resection, 2.7%; p <0.001).8 A subanalysis of the Japan Clinical Oncology Group 0802 also reported lower occult nodal detection rates in segmentectomy compared with lobectomy (3.4% versus 8.3%; p < 0.001).9 Although these reports analyzed a large number of cases, details of the LN dissection were lacking, and the area of improvement was not clearly reported.
In the present study, the comparison between lobectomy and segmentectomy revealed a statistically significant difference in the number and station count of harvested LNs and the occult nodal detection rate. However, it should be noted that the occult nodal detection rate was not different between the groups for the N2 detection rate, particularly when intraoperative conversion cases were categorized as segmentectomy. Theoretically, the extent of mediastinal node dissection is independent of the extent of lung resection, allowing the same quality of dissection even with sublobar resection. Previously reported differences in N2 node detection may be attributed to operator preferences in the context of sublobar resection, and there may be an effect of conversion to lobectomy on the basis of positive nodes detected with frozen sections. With appropriate attention, occult N2 disease can likely be detected with similar quality even in the setting of segmentectomy.
In contrast, the inferiority of dissection and occult node detection rate were more prominent in N1 LNs. Our analysis revealed that this difference was partially rooted in the LN from the lung specimen dissected by pathologists outside the operating room. This discrepancy in number may be difficult to improve, given the size difference of lung specimens, which could be up to five times larger with lower lobectomy than superior segmentectomy. Although LN drainage theoretically follows the segmental bronchus,10 this is not clinically confirmed, and “skip metastasis” to nodes outside resected segments could occur. In our cohort, the harvest of stations #10 and #11 was inferior in segmentectomy. Although this pattern may vary by institution or surgeon, a deliberate effort to improve N1 LN dissection is essential, even though ACS guidelines mandate sampling of only one N1 station.
Despite a somewhat inevitable inferiority from different specimen sizes, refined pathologic dissection may alleviate the disadvantage. It was reported that standard pathology practice frequently leaves a large number of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis.11 In this study, refined and standardized pathologic examination could retrieve additional nodes in 90% of the patients, and 11% of the patients underwent upstaging. Although it is unclear whether this type of intervention mitigates the disadvantage of smaller specimens in segmentectomy, it should be considered given the significantly lower occult node detection rate with specimens from segmentectomy. Future efforts should focus on establishing standardized, high-quality pathologic processing to optimize LN assessment.
Even with the challenge of pathologic harvesting, the inferior surgical LN harvest in N1 dissection and N2 nodes and the occult node detection rate with N1 dissection nodes warrant surgeons’ efforts to improve. One potential way of improvement is the RATS approach. The minimally invasive approach is now widely used in thoracic surgery, but the Society of Thoracic Surgeons database analysis in 2012 found an inferior occult node detection rate with the VATS approach compared with the thoracotomy approach (11.6% versus 14.3%).3 Since the emergence of the RATS approach over the previous decade, several institution-level reports found superior LN dissection with the RATS approach compared with the VATS approach,12,13 whereas proof with large database analysis is currently lacking. The effect of the surgical approach is dependent on each surgeon’s experience, and RATS is just an example of possible measures to improve LN harvesting. Surgeons should continue making efforts for better surgical staging in N1 LNs regardless of the surgical approach.
The quality measurement of LN dissection is a topic requiring further discussion. The ACOSOG Z0030 trial is still a landmark trial, which found no prognostic difference between LN sampling and dissection.14 However, more LN harvesting correlates with a higher occult nodal detection rate, and the extent of adequate LN count has been debated.7,8 The use of station count over LN count as a quality measure is another key consideration owing to the greater interevaluator variability in LN enumeration. The current ACS guidelines recommend a station-based sampling strategy as a minimum of one N1 station and three N2 stations sampled, whereas an analysis found only a marginal survival advantage over the previous recommendation (≥10 LNs).15 Likewise, our data did not reveal advantages in occult node detection or survival in the patients who met versus did not meet the current station-based sampling recommendation. Although the supporting evidence is not very strong, it is to be noted that these quality measures have improved the adherence to LN sampling guidelines over time, from 35.6% in 2006 to 49.1% in 2016,15 showing the importance of quality monitoring. Although further data collection is warranted, surgeons should continue high-quality LN dissection to achieve accurate staging and precise postoperative treatment selections.
The survival benefit of adjuvant chemotherapy in occult node-positive patients is consistent with previous reports.7,16 Given that one of the key advantages of extensive LN dissection is identifying high-risk patients who may benefit from adjuvant therapy, this finding is important. However, interpreting survival differences in this setting is complicated by selection bias, which warrants a deeper analysis beyond the scope of this article. To date, prospective studies have not definitively established the true benefit of adjuvant chemotherapy in patients with occult nodal disease.
This study has several limitations in addition to the retrospective design. First, our database lacks some radiographic (central location,17 presence of ground-glass component9) and pathologic variables (subtypes of adenocarcinoma,18 spread through airspace19) with the reported association with occult metastasis. Thus, our model is not perfect for predicting occult node metastasis and adjusting the risk of occult node metastasis, although it was not the primary objective of this study. Second, our inclusion criteria (tumor size ≤3 cm) were different from the criteria for segmentectomy (≤2 cm), most solidly supported by the randomized control trials. Our institutional data support segmentectomy for cT1c patients,20 as in other reports from Japan.21 The inclusion of 3 cm in this study would be helpful for the expanded application of segmentectomy, especially for patients with marginal physiological reserve. The compliance rate with ACS guidelines for LN sampling was relatively low in this cohort, but it is noted that the recommendations were implemented in 2021.22 Despite these limitations, the present study clarified the difference in LN dissection and occult node detection between lobectomy and segmentectomy, showing the direction of improvement in this topic.
In conclusion, occult LN metastasis is not a rare condition in clinical T1N0M0 NSCLC, even in tumors ≤1 cm in size. Segmentectomy was associated with less LN sampling, which translated into lower detection of occult nodal metastasis in N1 LNs. Although refined pathologic dissection could potentially improve detection, there may be an inevitable inferiority in LN sampling with segmentectomy.
CRediT Authorship Contribution Statement
Yota Suzuki: Conceptualization, Formal analysis, Writing - original draft.
Rajeev Dhupar: Conceptualization, Writing - original draft.
Inderpal S. Sarkaria: Writing - review & editing.
Ian G. Christie: Investigation.
Summer N. Mazur: Investigation.
Arjun Pennathur: Validation.
James D. Luketich: Writing - review & editing.
Ryan M. Levy: Writing - review & editing.
Rodney J. Landreneau: Conceptualization.
Matthew J. Schuchert: Project administration.
Informed Patient Consent and Consent to Publication
Approval for this study was obtained from the institutional review board of the University of Pittsburgh (STUDY20050076), which waived the requirement for individual patient consent.
Disclosure
The authors declare no conflict of interest.
Acknowledgments
We acknowledge funding from the Sampson Family Endowed Chair in Thoracic Surgical Oncology at the University of Pittsburgh (AP).
Footnotes
Cite this article as: Suzuki Y, Dhupar R, Sarkaria IS, et al. Occult node detection with lobectomy versus segmentectomy for stage IA NSCLC. JTO Clin Res Rep 2025;6:100861.
Note: To access the supplementary material accompanying this article, visit the online version of the JTO Clinical and Research Reports at www.jtocrr.org and at https://doi.org/10.1016/j.jtocrr.2025.100861.
Supplementary Data
Supplementary Figure 1.
Supplementary Figure.
2
Supplementary Figure 3.
References
- 1.Altorki N., Wang X., Kozono D., et al. Lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer. N Engl J Med. 2023;388:489–498. doi: 10.1056/NEJMoa2212083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Saji H., Okada M., Tsuboi M., et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet. 2022;399:1607–1617. doi: 10.1016/S0140-6736(21)02333-3. [DOI] [PubMed] [Google Scholar]
- 3.Boffa D.J., Kosinski A.S., Paul S., Mitchell J.D., Onaitis M. Lymph node evaluation by open or video-assisted approaches in 11,500 anatomic lung cancer resections. Ann Thorac Surg. 2012;94:347–353. doi: 10.1016/j.athoracsur.2012.04.059. [DOI] [PubMed] [Google Scholar]
- 4.Silvestri G.A., Gonzalez A.V., Jantz M.A., et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S–e250S. doi: 10.1378/chest.12-2355. [DOI] [PubMed] [Google Scholar]
- 5.Schmidt-Hansen M., Baldwin D.R., Hasler E., Zamora J., Abraira V., Roqué I., Figuls M. PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. Cochrane Database Syst Rev. 2014;2014:CD009519. doi: 10.1002/14651858.CD009519.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kohman L.J., Gu L., Altorki N., et al. Biopsy first: lessons learned from Cancer and Leukemia Group B (CALGB) 140503. J Thorac Cardiovasc Surg. 2017;153:1592–1597. doi: 10.1016/j.jtcvs.2016.12.045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Razi S.S., Nguyen D., Villamizar N. Lobectomy does not confer survival advantage over segmentectomy for non-small cell lung cancer with unsuspected nodal disease. J Thorac Cardiovasc Surg. 2020;159:2469–2483.e4. doi: 10.1016/j.jtcvs.2019.10.165. [DOI] [PubMed] [Google Scholar]
- 8.Mynard N., Nasar A., Rahouma M., et al. Extent of resection influences survival in early-stage lung cancer with occult nodal disease. Ann Thorac Surg. 2022;114:959–967. doi: 10.1016/j.athoracsur.2022.01.038. [DOI] [PubMed] [Google Scholar]
- 9.Maniwa T., Okami J., Miyoshi T., et al. Lymph node dissection in small peripheral lung cancer: supplemental analysis of JCOG0802/WJOG4607L. J Thorac Cardiovasc Surg. 2024;168:674–683.e1. doi: 10.1016/j.jtcvs.2023.11.023. [DOI] [PubMed] [Google Scholar]
- 10.Kim A.W. Lymph node drainage patterns and micrometastasis in lung cancer. Semin Thorac Cardiovasc Surg. 2009;21:298–308. doi: 10.1053/j.semtcvs.2009.11.001. [DOI] [PubMed] [Google Scholar]
- 11.Ramirez R.A., Wang C.G., Miller L.E., et al. Incomplete intrapulmonary lymph node retrieval after routine pathologic examination of resected lung cancer. J Clin Oncol. 2012;30:2823–2828. doi: 10.1200/JCO.2011.39.2589. [DOI] [PubMed] [Google Scholar]
- 12.Haruki T., Takagi Y., Kubouchi Y., et al. Comparison between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery for mediastinal and hilar lymph node dissection in lung cancer surgery. Interact Cardiovasc Thorac Surg. 2021;33:409–417. doi: 10.1093/icvts/ivab112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Toker A., Özyurtkan M.O., Demirhan Ö., Ayalp K., Kaba E., Uyumaz E. Lymph node dissection in surgery for lung cancer: comparison of open vs. video-assisted vs. robotic-assisted approaches. Ann Thorac Cardiovasc Surg. 2016;22:284–290. doi: 10.5761/atcs.oa.16-00087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Darling G.E., Allen M.S., Decker P.A., et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011;141:662–670. doi: 10.1016/j.jtcvs.2010.11.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Heiden B.T., Eaton D.B., Jr., Chang S.H., et al. Assessment of updated commission on cancer guidelines for intraoperative lymph node sampling in early stage NSCLC. J Thorac Oncol. 2022;17:1287–1296. doi: 10.1016/j.jtho.2022.08.009. [DOI] [PubMed] [Google Scholar]
- 16.Deng J., Zhong Y., Wang T., et al. Lung cancer with PET/CT-defined occult nodal metastasis yields favourable prognosis and benefits from adjuvant therapy: a multicentre study. Eur J Nucl Med Mol Imaging. 2022;49:2414–2424. doi: 10.1007/s00259-022-05690-3. [DOI] [PubMed] [Google Scholar]
- 17.Lee P.C., Port J.L., Korst R.J., Liss Y., Meherally D.N., Altorki N.K. Risk factors for occult mediastinal metastases in clinical Stage I non-small cell lung cancer. Ann Thorac Surg. 2007;84:177–181. doi: 10.1016/j.athoracsur.2007.03.081. [DOI] [PubMed] [Google Scholar]
- 18.Hung J.J., Yeh Y.C., Jeng W.J., Wu Y.C., Chou T.Y., Hsu W.H. Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller. Eur J Cardiothorac Surg. 2016;50:329–336. doi: 10.1093/ejcts/ezv485. [DOI] [PubMed] [Google Scholar]
- 19.Vaghjiani R.G., Takahashi Y., Eguchi T., et al. Tumor spread through air spaces is a predictor of occult lymph node metastasis in clinical stage IA lung adenocarcinoma. J Thorac Oncol. 2020;15:792–802. doi: 10.1016/j.jtho.2020.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Chan E.G., Chan P.G., Mazur S.N., et al. Outcomes with segmentectomy versus lobectomy in patients with clinical T1cN0M0 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2021;161:1639–1648.e2. doi: 10.1016/j.jtcvs.2020.03.041. [DOI] [PubMed] [Google Scholar]
- 21.Hattori A., Matsunaga T., Fukui M., Takamochi K., Oh S., Suzuki K. Oncologic outcomes of segmentectomy for stage IA radiological solid-predominant lung cancer >2 cm in maximum tumour size. Interact Cardiovasc Thorac Surg. 2022;35 doi: 10.1093/icvts/ivac246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Nissen A.P., Vreeland T.J., Teshome M., et al. American College of Surgeons Commission on Cancer Standard for Curative-intent Pulmonary Resection. Ann Thorac Surg. 2022;113:5–8. doi: 10.1016/j.athoracsur.2021.05.051. [DOI] [PubMed] [Google Scholar]