Spatial classification of clinical T1a–bN0 non-small cell lung cancer in superior segment based on three-dimensional reconstruction: optimizing surgical margin and operative strategy

Introduction

Lung cancer remains one of the leading causes of cancer-related mortality worldwide (1). With the widespread use of thin-section computed tomography (CT) (2), an increasing number of early-stage lung cancers have been detected. Over the past two decades, sublobar resection has become a key surgical option for patients with early-stage non-small cell lung cancer (NSCLC).

Multiple randomized controlled trials (RCTs) have demonstrated that sublobar resection provides oncologic outcomes comparable to those of lobectomy while better preserving functional lung tissue. The CALGB140503 trial revealed that among patients with peripheral NSCLC tumors measuring ≤2 cm in diameter, sublobar resection resulted in similar 5-year disease-free survival (DFS) and overall survival (OS) compared to lobectomy (3), along with superior preservation of pulmonary function. Although the overall recurrence rates between the two approaches were not significantly different, a higher rate of local recurrence (LR) was observed after sublobar resection (3). Furthermore, the JCOG0802 trial reported that segmentectomy achieved non-inferior recurrence-free survival (RFS) compared to lobectomy in patients with peripheral NSCLC tumors ≤2 cm and a consolidation-to-tumor ratio (CTR) >0.5 on thin-section CT (4). Notably, segmentectomy was associated with superior OS. However, a higher incidence of LR was again noted in the segmentectomy group (4). Supplementary analysis identified pure solid appearance on thin-section CT, a surgical margin smaller than the tumor diameter, and male sex as independent risk factors for LR after segmentectomy (5).

In addition, several retrospective studies have highlighted a close correlation between tumor location and the risk of LR. For example, Nishio et al. (6) found that tumors located in the right upper lobe and those in bilateral basal segments were associated with relatively high LR rates of 21.9% and 20.8%, respectively. In contrast, Jones et al. (7) reported that right superior segment (S⁶) tumors had the highest LR rate (9.0%), while left upper division tumors had the lowest (3.4%). Handa et al. (8) observed a poorer prognosis in patients with S⁶ tumors compared to those with basal segment tumors, which was accompanied by a higher frequency of mediastinal lymph node metastases. Furthermore, Watanabe et al. (9) identified distinct lymphatic metastasis pathways between the superior and basal segments of the lower lobe, which may influence prognosis. These findings collectively suggest a high propensity for LR and poor prognosis following resection of S⁶. They also provide preliminary insights into potential mechanisms, such as unique tumor biology and lymphatic dissemination patterns associated with S⁶ tumors.

It is generally believed that the technical complexity of segmentectomy depends on the specific segments being resected. Specifically, complex segmentectomies demand greater surgical expertise than simple segmentectomies, which may contribute to higher rates of postoperative complications and LR (10,11). For example, segmentectomies involving the bilateral S⁶ segments, the apicoposterior segment of the left upper lobe, and the left lingular segment are often considered technically less challenging than those involving the right upper segments or basal segments (12). However, resection of the S⁶ segment is frequently associated with inadequate surgical margins, which may contribute to its relatively high LR rate. The supplementary analysis of JCOG0802 revealed that the surgical margin for left S⁶ segmentectomy was significantly smaller than that for other left-sided segments, with 24.1% of patients exhibiting a margin distance smaller than the tumor diameter (5). Similarly, Jones et al. (7) found that surgical margins following bilateral S⁶ segmentectomies were generally insufficient. They recommended that the surgical margin to tumor diameter ratio in right S⁶ segmentectomy should reach 1.5 to achieve better survival outcomes. However, the factors leading to insufficient surgical margins in S⁶ segmentectomy have not been systematically investigated. Therefore, this study aims to establish a three-dimensional (3D) spatial classification system for S⁶ tumors to analyze margin adequacy and optimize surgical planning.

The 3D reconstruction software used in The First Affiliated Hospital of Nanjing Medical University, “InFerVision”, has been widely adopted and validated in clinical practice. For instance, Bian et al. (13) employed “InFerVision” to analyze the morphological variations of lower lobe segments and their influence on the venous drainage patterns of V⁶b2 and V⁶b3. Subsequently, the same research team applied this platform and proposed the concept of inter-multisegmental veins (IMSVs) for the first time (14).

This study aims to resolve the problem of insufficient surgical margins in S⁶ segmentectomies. It is expected to improve preoperative planning and surgical strategies for sublobar resections in S⁶ NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2401/rc).

Methods

Study cohort

This retrospective cohort study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Review Board of The First Affiliated Hospital of Nanjing Medical University (No. 2025-SR-1172), and individual consent for this retrospective analysis was waived.

We retrospectively analyzed clinical data of patients with clinical T1a–bN0 S⁶ NSCLC who underwent thoracoscopic surgery between December 2019 and December 2023. Inclusion criteria were as follows: (I) complete DICOM data of preoperative chest CT; (II) diagnosis of clinical T1a–bN0 S⁶ NSCLC; (III) underwent thoracoscopic S⁶ segmentectomy, extended S⁶ segmentectomy, or combined resection of S⁶ or mono subsegment of S⁶ plus adjacent subsegments (with up to two additional wedge resections in the ipsilateral lung permitted); and (IV) solitary lesion located in the lower lobe. Exclusion criteria included: (I) incomplete clinical information; (II) unsatisfactory CT or 3D CT bronchography and angiography (3D-CTBA) image quality; (III) multiple lesions in the lower lobe; and (IV) maximum tumor diameter >2 cm. Ultimately, 699 patients were eligible for analysis (Figure 1).

Figure 1 Flow chart of patient selection. S⁶: superior segment; S^6c: including combined resection of S⁶ or mono subsegment of S⁶ plus adjacent subsegments, such as resection of S^6+8a or S^6b+8a; S⁶ⁿ: including mono S⁶ segmentectomy and extended S⁶ segmentectomy. 3D-CTBA, three-dimensional computed tomography bronchography and angiography; CT, computed tomography; CTR, consolidation-to-tumor ratio; NSCLC, non-small cell lung cancer.

3D reconstruction

The CT images were transformed into 3D-CTBA images using the “InferVision” software (15). The software automatically generated the lesion and its associated 2 cm simulative cutting margin. This margin took the form of a quasi-sphere, resembling the lesion’s shape, and was uniformly expanded by 2 cm from the lesion’s outer surface.

Measurement method of CTR and depth ratio

The CTR was quantified using thin-slice CT images in lung window settings. Consolidation was defined as an area of increased opacification that completely obscured underlying vascular structures, while ground-glass opacity (GGO) was identified as hazy increased attenuation without obscuration of vascular patterns. The CTR was calculated as the ratio of the maximum consolidation diameter to the maximum tumor dimension (16). Depth ratio measurements were performed by first identifying the bronchial opening’s center (O) in the lobar cross-section. A radial line was drawn from O to the lesion’s center (A) and extended to the pleural surface (B). The OB distance was divided into three equal segments representing inner (0–33.3%), middle (33.4–66.6%), and outer (66.7–100%) lung regions. The depth ratio was calculated as BA/BO (17) (Figure 2).

Figure 2 Measurement of the depth ratio in a 3D-CTBA image. A: the center of the lesion; B: the point where the radial line drawing from O to A extended to the pleural surface; O: the center of the bronchial opening of the lobe to which the tumor belongs. 3D-CTBA, three-dimensional computed tomography bronchography and angiography.

Definition of the intersegmental plane

Based on previous anatomical studies (18,19) and The First Affiliated Hospital of Nanjing Medical University’s clinical experience (20), intersegmental boundaries between S⁶ and basal segments were defined according to the intersegmental veins: V⁶b2 (between S⁶b and S⁹a), V⁶b3 (between S⁶b and S⁸a), and V⁶c [between S⁶c and S¹⁰a or S* (S⁷b when B⁷ is B⁷ab type or B⁷b type in the right lower lobe)]. In this study, we used the “InferVision” software to simulate the volume of each lung segment in the lower lobe and to identify the intersegmental plane between the S⁶ segment and the basal segments (Figure 3). During surgery, the intersegmental plane was identified using either a modified inflation-deflation method or indocyanine green (ICG) fluorescence staining (21,22). The modified inflation-deflation method requires a waiting period of several minutes but produces a relatively clear and stable boundary. In contrast, ICG fluorescence staining provides rapid visualization of the plane, though the effect is transient and requires immediate marking with electrocautery.

Figure 3 Demonstration of the intersegmental plane based on intersegmental veins (A) and the relative volume of the lower lobe segments (B). S*: subsuperior segment; S⁶: superior segment; S⁸: anterior basal segment; S⁹: lateral basal segment; S¹⁰: posterior basal segment; V⁶b2: intersegmental vein between S⁶b and S⁹a; V⁶b3: intersegmental vein between S⁶b and S⁸a; V⁶c: intersegmental vein between S⁶c and S¹⁰a or S* (S⁷b when B⁷ is B⁷ab type or B⁷b type in the right lower lobe).

Spatial classification system

Based on 3D reconstructed anatomical relationships between the simulated 2 cm cutting margin sphere and adjacent structures, we established a novel spatial classification system for S⁶ NSCLC (Figure 4):

• S⁶-I: margin sphere located above the intersegmental plane;
• S⁶-II: margin sphere extended below the intersegmental plane;
• S⁶-IIa: margin sphere didn’t involve main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a);
• S⁶-IIb: margin sphere involved main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a);
• S⁶-III: margin sphere involved main trunks of the lower lobe (e.g., A^7-10 or B^7-10).

Figure 4 Demonstration of the S⁶-I group (A,B), the S⁶-IIa group (C,D), the S⁶-IIb group (E,F), and the S⁶-III group (G,H). S⁶-I: margin sphere located above the intersegmental plane; S⁶-IIa: margin sphere did not involve main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a); S⁶-IIb: margin sphere involved main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a); S⁶-III: margin sphere involved main trunks of the lower lobe (e.g., A^7-10 or B^7-10). A^7-10: basal segmental artery; A⁸a: lateral subsegmental artery of the anterior basal segmental artery; B^7-10: basal segmental bronchus; B⁸a: lateral subsegmental bronchus of the anterior basal segmental bronchus; S*: subsuperior segment; S⁶: superior segment; V⁶b2: intersegmental vein between S⁶b and S⁹a; V⁶b3: intersegmental vein between S⁶b and S⁸a; V⁶c: intersegmental vein between S⁶c and S¹⁰a or S* (S⁷b when B⁷ is B⁷ab type or B⁷b type in the right lower lobe).

Evaluation of surgical methods and margin

Surgical approaches for S⁶ NSCLC were categorized into two types: segment-based S⁶ resection (S⁶ⁿ) and subsegment-based S⁶ resection (S^6c). S⁶ⁿ included mono S⁶ segmentectomy and extended S⁶ segmentectomy. Extended S⁶ segmentectomy was defined as resection of S⁶ crossing the intersegmental plane with partial removal of adjacent segments, while preserving the main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a) (23). S^6c referred to combined resection of S⁶ or mono subsegment of S⁶ plus adjacent subsegments, such as resection of S^6+8a or S^6b+8a. In S^6c procedures, the main subsegmental structures of the basal segments (e.g., A⁸a and B⁸a) were explicitly transected. For surgical margin measurement, the pleural surface-based margin distance method described by Goldstein et al. (24) was adopted. During surgery, all specimens were kept intact and measured fresh. The pleural surface-based margin distance was defined as the shortest vertical distance from the edge of the palpated tumor to the staple line, which was measured using a ruler placed on the pleural surface. All surgical margin measurements were jointly determined by two experienced thoracic surgeons, and the specimens were immediately sent for frozen section analysis after measurement. To comprehensively evaluate margin adequacy, the following variables were calculated: margin/diameter ratio, margin distance ≥2 cm, and margin/diameter ratio ≥1.

Statistical analysis

Statistical analyses were performed using R software (version 4.3.0). For normally distributed continuous variables, data were expressed as mean ± standard deviation (SD). Comparisons between the two groups were conducted using the t-test, and comparisons among multiple groups were performed using the analysis of variance (ANOVA) test. For non-normally distributed continuous variables, data were presented as median (1^st quartile, 3^rd quartile). The Mann-Whitney test was used for comparisons between two groups, and the Kruskal-Wallis test was applied for multiple groups. Categorical variables were presented as number (%) and analyzed by the χ² test or Fisher’s exact test. A two-sided P value <0.05 was considered statistically significant.

Results

Patients and clinical characteristics of the study cohort

Among the 699 eligible patients, 388 (55.5%) were classified as S⁶-I, 248 (35.5%) as S⁶-II, and 63 (9.0%) as S⁶-III (Table 1). Sex distribution differed significantly among the three groups (P<0.001), with the proportion of females being highest in S⁶-III (84.1%), followed by S⁶-II (73.0%) and S⁶-I (62.4%). A significant difference was also observed in depth ratio (P<0.001) (Table 1). In S⁶-I and S⁶-II, no cases were found in the inner region. The outer region accounted for 64.7% and 58.1%, respectively, while the middle region accounted for 35.3% and 41.9%. In S⁶-III, no cases were found in the outer region; 65.1% were in the middle region, and 34.9% in the inner region. Of the three groups, variables such as age, smoking history, pulmonary comorbidity, cardiac comorbidity, side, and CTR did not demonstrate statistical significance (P=0.41, P=0.051, P=0.84, P=0.71, P=0.18, and P=0.49) (Table 1).

In the analysis of operative and pathology characteristics, surgical methods varied significantly among the three groups (P<0.001) (Table 2). In S⁶-I, 385 cases (99.2%) underwent S⁶ⁿ, 3 cases (0.8%) underwent S^6c. In S⁶-II, 207 cases (83.5%) underwent S⁶ⁿ, 41 cases (16.5%) underwent S^6c. In S⁶-III, 55 cases (87.3%) underwent S⁶ⁿ, 8 cases (12.7%) underwent S^6c. Among the three groups, surgical margin-related variables such as margin distance, margin distance ≥2 cm, margin/diameter ratio, and margin/diameter ratio ≥1 were statistically significant (P<0.001) (Table 2). In S⁶-I, the median margin was 2.50 cm [interquartile range (IQR), 2.00 to 3.50 cm], with 85.6% of cases having a margin distance ≥2 cm and 99.0% having a margin/diameter ratio ≥1. In S⁶-II, the median margin was 1.80 cm (IQR, 1.30 to 2.20 cm), with 48.0% of cases having a margin distance ≥2 cm and 85.9% having a margin/diameter ratio ≥1. By contrast, in S⁶-III, the median margin was 1.00 cm (IQR, 0.70 to 1.20 cm); none of the cases had a margin distance ≥2 cm, and only 57.1% had a margin/diameter ratio ≥1. No significant differences were observed for histology and tumor diameter (P=0.39 and P=0.74) (Table 2).

Subanalysis of the S⁶-III group

Given that S⁶-III cases had the narrowest surgical margins, we further examined whether the surgical approach influenced margin outcomes by dividing them into S⁶ⁿ and S^6c subgroups. In the S⁶ⁿ subgroup, the median surgical margin was 1.00 cm (IQR, 0.75 to 1.20 cm), the margin/diameter ratio was 1.11 (IQR, 0.71 to 1.50), and 32 cases (58.2%) had a margin/diameter ratio ≥1 (Table 3). While in the S^6c subgroup, the median surgical margin was 0.90 cm (IQR, 0.57 to 1.02 cm), the margin/diameter ratio was 0.92 (IQR, 0.79 to 1.24), and 4 cases (50.0%) had a margin/diameter ratio ≥1 (Table 3). No statistically significant differences were observed in margin distance, margin/diameter ratio, and margin/diameter ratio ≥1 between the two subgroups (P>0.05) (Table 3).

Subanalysis of the S⁶-II group

Patients in S⁶-II were subdivided into S⁶-IIa and S⁶-IIb based on whether the margin sphere involved the main subsegmental structures of the basal segments (e.g., A⁸a or B⁸a). This subanalysis included 248 patients, with 173 (69.8%) in S⁶-IIa and 75 (30.2%) in S⁶-IIb (Table 4). Significant differences between the two groups were observed in depth ratio, surgery, margin distance, margin distance ≥2 cm, margin/diameter ratio, and margin/diameter ratio ≥1 (P<0.001) (Table 4). Compared to S⁶-IIa, S⁶-IIb had a higher proportion of the middle region (70.7% vs. 29.5%) and a lower proportion of the outer region (29.3% vs. 70.5%) in the depth ratio. For surgical methods, in S⁶-IIa, 165 cases (95.4%) underwent S⁶ⁿ, and only 8 cases (4.6%) underwent S^6c. While in S⁶-IIb, 42 cases (56.0%) underwent S⁶ⁿ, and 33 cases (44.0%) underwent S^6c. S⁶-IIa had a higher median margin [2.00 cm (IQR, 1.50 to 2.50 cm)] compared to S⁶-IIb [1.40 cm (IQR, 0.80 to 1.75 cm)]. Similarly, the median margin/diameter ratio was higher in S⁶-IIa [2.00 (IQR, 1.54 to 2.67)] than in S⁶-IIb [1.30 (IQR, 0.75 to 2.00)]. In S⁶-IIa, 101 cases (58.4%) have a margin distance ≥2 cm, which is higher than the 18 cases (24.0%) in S⁶-IIb. Furthermore, 165 cases (95.4%) in S⁶-IIa have a margin/diameter ratio ≥1, compared to 48 cases (64.0%) in S⁶-IIb. No significant differences were found for side, CTR, histology, and tumor diameter (P>0.05) (Table 4).

We further divided S⁶-IIb cases into two subgroups based on surgical methods: S⁶ⁿ and S^6c (Table 5). In S⁶-IIb, the median surgical margin for S^6c was 1.80 cm (IQR, 1.50 to 2.00 cm), higher than that of S⁶ⁿ [0.80 cm (IQR, 0.60 to 1.37 cm)] (P<0.001) (Table 5). Similarly, the median margin/diameter ratio was higher in S^6c [1.88 (IQR, 1.25 to 2.50)] than that of S⁶ⁿ [0.80 (IQR, 0.62 to 1.40)] (P<0.001). Among the 33 cases undergoing S^6c, 16 (48.5%) had a margin distance ≥2 cm, and 31 (93.9%) had a margin/diameter ratio ≥1. In contrast, among the S⁶ⁿ cases, only 2 (4.8%) had a margin distance ≥2 cm, and 17 (40.5%) had a margin/diameter ratio ≥1. The differences between the two groups were statistically significant (P<0.001) (Table 5).

Discussion

With the increasing use of sublobar resection for early-stage lung cancer, the optimal surgical margin has become a key clinical concern. The JCOG0802 trial required a margin distance ≥2 cm or a margin/diameter ratio ≥1 for eligibility; patients who did not meet these criteria or had positive margins were excluded (4). The supplementary analysis further confirmed that a margin/diameter ratio <1 was an independent risk factor for LR after segmentectomy (5). In contrast, the JCOG0804 trial suggested that for tumors ≤2 cm in diameter and with a CTR ≤0.25, a margin ≥5 mm was sufficient (25). A narrative review focused on surgical margin in sublobar resection identified six studies that examined the association between the margin/diameter ratio and postoperative recurrence, most of which indicated that the ratio <1 was a significant predictor of recurrence or reduced survival (26). Based on these studies, we included variables such as margin distance, margin/diameter ratio, margin distance ≥2 cm, and margin/diameter ratio ≥1 to evaluate the adequacy of the surgical margin.

Among the three groups, S⁶-I showed significantly larger surgical margins than S⁶-II and S⁶-III. This difference was likely due to the surgical method used. In S⁶-I, all cases had margin spheres located above the intersegmental plane. Most cases (385, 99.2%) underwent S⁶ⁿ, which is a straightforward segmental resection that often obtains a larger surgical margin. In S⁶-II, the surgical margin distances fell between those of S⁶-I and S⁶-III. In S⁶-III, the margin spheres were located deeper in 3D space and involved main trunks of the lower lobe. Notably, performing S^6c in these cases did not yield better surgical margins than S⁶ⁿ. Therefore, for cases classified as S⁶-III, a thorough evaluation of factors including CTR, age, gender, general health status, and pulmonary function reserve is necessary to determine whether to perform lobectomy. The subanalysis of S⁶-II showed that cases in S⁶-IIa often had higher surgical margins compared to S⁶-IIb. Among the 173 cases in S⁶-IIa, 165 (95.4%) underwent S⁶ⁿ, and 8 (4.6%) underwent S^6c. Moreover, 165 cases (95.4%) had a margin/diameter ratio ≥1, indicating that most cases met the surgical margin requirement. Therefore, we believe that when the tumor’s margin sphere extends beyond the intersegmental plane but does not involve main subsegmental structures of the basal segments, surgery can be planned in units of S⁶, such as S⁶ segmentectomy or extended S⁶ segmentectomy. Among the 75 cases in S⁶-IIb, 42 (56.0%) underwent S⁶ⁿ, 33 (44.0%) underwent S^6c. Patients undergoing S^6c had higher surgical margins compared to those undergoing S⁶ⁿ. Therefore, we believe that if the margin sphere extends beyond the intersegmental plane and involves main subsegmental structures of the basal segments, surgery should be planned by subsegment to ensure sufficient surgical margins. For example, performing S^6c, such as resection of S^6+8a, may be necessary.

Our study revealed statistically significant differences in depth ratio across all spatial groups, indicating that this parameter may serve as an auxiliary indicator for spatial classification and, indirectly, for surgical planning. Among the 395 cases in the outer region, 251 (63.5%) were classified as S⁶-I, 122 (30.9%) as S⁶-IIa, and only 22 (5.6%) as S⁶-IIb, with no cases belonging to S⁶-III. Therefore, for most tumors located in the outer region, performing S⁶ⁿ is sufficient to achieve an adequate surgical margin. Among the 282 cases in the middle region, 137 (48.6%) were S⁶-I, 51 (18.1%) were S⁶-IIa, 53 (18.8%) were S⁶-IIb, and 41 (14.5%) were S⁶-III. All 22 cases in the inner region belonged to S⁶-III. Consequently, tumors located in the middle or inner regions often have margin spheres involving more anatomical structures. In such cases, performing S^6c or even lobectomy may be necessary to obtain an adequate surgical margin.

This study presents a new spatial classification system using 3D reconstruction technology to evaluate the surgical margin in S⁶ segmentectomy for early-stage NSCLC. Our key findings demonstrate that the spatial relationship between the tumor margin sphere and adjacent anatomical structures significantly influences the surgical margin. Specifically, our analysis showed that the S⁶-III group exhibited the smallest margin distances, often failing to meet the recommended threshold of a margin/diameter ratio ≥1, whereas the S⁶-I group consistently achieved sufficient surgical margins. These results highlight the critical role of preoperative 3D reconstruction in optimizing surgical strategies for sublobar resection.

Our findings align with prior researches which emphasized the technical challenges of segmentectomy. Specifically, the JCOG0802 and CALGB140503 trials established the non-inferiority of segmentectomy to lobectomy in OS and RFS, but noted higher LR rates, partly attributable to insufficient surgical margins (3,4). For instance, both Jones et al. and the supplementary analysis of JCOG0802 identified inadequate surgical margins in S⁶ segmentectomies (5,7), consistent with our observations in the S⁶-III and S⁶-IIb groups. The spatial classification system proposed here extends these insights by quantifying how tumor location relative to adjacent anatomical structures influences margin outcomes. For example, the S⁶-IIb subgroup, in which the margin sphere involved main subsegmental structures of the basal segments, required S^6c to achieve adequate surgical margins.

Several anatomical variations inherent to pulmonary structures likely influence the outcomes of our study. First, notable differences exist in bronchial angles and segmental distribution between the upper and lower lobes. The angles between the bronchi in the upper lobe are often larger and display a radial distribution, which comparatively facilitates surgical planning for combined segmentectomy or subsegmentectomy. In contrast, the angles between the bronchi in the lower lobe are relatively smaller and exhibit converging patterns, which make surgical planning for combined segmentectomy or subsegmentectomy more challenging. Consequently, compared to the upper lobe, a greater number of segments or subsegments are often required for resection in the lower lobe to achieve sufficient surgical margins. Additionally, the subsuperior segment (S*), an atypical segment of the lower lobe, can affect the anatomical recognition and naming of the remaining segments in the lower lobe, thus influencing surgical planning. Zhou et al. (27) conducted the first large-sample research on the prevalence and anatomical features of S*. They found that the incidence of S* was approximately 32.04%, with various anatomical types. The volume of S* was smaller than other segments of the lower lobe, and it was closer in size to a subsegment. Therefore, in our study, we considered S* as an independent subsegment structure between the superior and basal segments. If the surgical margin sphere involves main trunks of S* (A* or B*), it is classified into the S⁶-IIb group and requires resection of S⁶ plus S* to ensure an adequate surgical margin. Moreover, venous variations are frequently observed in the S⁶ segment. Specifically, The First Affiliated Hospital of Nanjing Medical University has previously studied the prevalence, reflux patterns, and clinical significance of V⁶ (13,28). The reflux patterns and variations in the intersegmental veins (V⁶b2, V⁶b3, V⁶c) often lead to changes in the intersegmental plane, which also affect surgical planning. Furthermore, some intersegmental veins were not visible in the 3D-CTBA images of this study. In such instances, the intersegmental plane could only be predicted based on the anatomical distribution of arteries and bronchi. Therefore, we plan to further investigate the impact of different anatomical variations on S⁶ surgical planning in future studies.

Several limitations of this study should be acknowledged. First, the retrospective design may introduce selection bias, despite rigorous inclusion criteria. Second, the single-center cohort and relatively small sample size (e.g., S⁶-III, n=63) limit generalizability. Third, although 3D reconstruction with “InferVision” software provides precise anatomical mapping, its reliance on CT image quality and equipment requires validation across multiple centers. Future prospective studies should focus on standardizing 3D-based classification and evaluating its impact on long-term outcomes, such as RFS and DFS.

Conclusions

This study establishes a 3D-driven spatial classification system that effectively stratifies surgical margin risk in S⁶ segmentectomies. By identifying cases requiring subsegment-based resections or lobectomies, this system enhances the accuracy and safety of precision surgery for S⁶ NSCLC.

Acknowledgments

The authors thank all the study participants, research staff, and students who participated in this study and greatly appreciate the assistance of the AME Thoracic Surgery Collaborative Group and associated organizations.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2401/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2401/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2401/prf

Funding: This study was supported by the National Science Foundation of China (No. 62471122).

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-2401/coif). The authors have no conflicts of interest to declare.

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. The study protocol was approved by the Ethics Review Board of The First Affiliated Hospital of Nanjing Medical University (No. 2025-SR-1172), and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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