Prognostic value of a three-dimensional spatial classification system for clinical T1a-bN0 non-small cell lung cancer in the superior segment.
- 1Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract
Recurrence after segmentectomy in non-small cell lung cancer (NSCLC) remains a clinical challenge, particularly for tumors in the superior segment of the lower lobe (S6). We hypothesized that this was attributable to the unique spatial location of S6 tumors and the difficulty in achieving adequate surgical margins. Therefore, we developed a three-dimensional (3D) spatial classification system for S6 tumors and investigated its prognostic value. This retrospective cohort study included 916 patients with clinical T1a-bN0 S6 NSCLC who underwent thoracoscopic segmentectomy from August 2015 to April 2023. Tumors were classified into four groups (S6-I to S6-IV) based on the relationship between a simulated 2-cm margin sphere and adjacent anatomical structures: S6-I (margin sphere located above the intersegmental plane), S6-II (margin sphere extended below the intersegmental plane but did not involve main subsegmental structures of the basal segments), S6-III (margin sphere extended below the intersegmental plane and involved main subsegmental structures of the basal segments), and S6-IV (margin sphere involved main trunks of the lower lobe). Surgical methods were categorized as S6 segmentectomy (S6-Seg; including isolated and extended S6 segmentectomy) or combined S6 subsegmentectomy (S6-Comb; combined resection of S6 or its subsegments plus adjacent subsegments, such as resection of S6+8a or S6b+8a). The primary endpoint was recurrence-free survival (RFS). Counterfactual mediation analysis was conducted to assess the mediating role of margin distance. The 5-year RFS rates were 96.9% for S6-I, 95.3% for S6-II, 81.5% for S6-III, and 76.6% for S6-IV (log-rank P<0.001). In multivariable analysisadjusted for age, consolidation-to-tumor ratio (CTR), and tumor size, spatial classification was independently associated with RFS [S6-III vs. S6-I: hazard ratio (HR) =5.30, P<0.001; S6-IV vs. S6-I: HR =5.11, P<0.001]. Counterfactual mediation analysis demonstrated that the association between spatial classification and RFS was largely mediated by margin distance [proportion mediated (PM), 84.0% and 92.0% for S6-III vs. S6-I and S6-IV vs. S6-I, respectively]. In the S6-III subgroup, S6-Comb was associated with superior RFS compared with S6-Seg [HR =0.23, 95% confidence interval (CI): 0.07-0.78, P=0.02], an effect partly mediated by margin distance. In the S6-IV subgroup, surgical method was not associated with RFS. The spatial classification system effectively stratifies recurrence risk in S6 NSCLC. Its association with recurrence is largely mediated by surgical margin distance, but its primary strength lies in preoperative risk prediction. We propose a preliminary, anatomy-guided hypothesis-generating algorithm: S6-Seg for S6-I and S6-II tumors, S6-Comb for S6-III tumors, and consideration of lobectomy for S6-IV tumors,which requires validation in prospective studies.
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BibTeX
@article{yang2026prognostic,
title = {{Prognostic value of a three-dimensional spatial classification system for clinical T1a-bN0 non-small cell lung cancer in the superior segment.}},
author = {Yihan Yang and Angat Naresh Chadha and Yingchao Gu and Ruizhi Gong and Qianrui Ren and Xinfeng Xu and Wei Wen and Zhibo Wang and Quan Zhu},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-0934},
url = {https://europepmc.org/article/MED/42999403},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Prognostic value of a three-dimensional spatial classification system for clinical T1a-bN0 non-small cell lung cancer in the superior segment.
AU - Yihan Yang
AU - Angat Naresh Chadha
AU - Yingchao Gu
AU - Ruizhi Gong
AU - Qianrui Ren
AU - Xinfeng Xu
AU - Wei Wen
AU - Zhibo Wang
AU - Quan Zhu
PY - 2026
DA - 2026/09/29
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0934
UR - https://europepmc.org/article/MED/42999403
AB - Recurrence after segmentectomy in non-small cell lung cancer (NSCLC) remains a clinical challenge, particularly for tumors in the superior segment of the lower lobe (S6). We hypothesized that this was attributable to the unique spatial location of S6 tumors and the difficulty in achieving adequate surgical margins. Therefore, we developed a three-dimensional (3D) spatial classification system for S6 tumors and investigated its prognostic value. This retrospective cohort study included 916 patients with clinical T1a-bN0 S6 NSCLC who underwent thoracoscopic segmentectomy from August 2015 to April 2023. Tumors were classified into four groups (S6-I to S6-IV) based on the relationship between a simulated 2-cm margin sphere and adjacent anatomical structures: S6-I (margin sphere located above the intersegmental plane), S6-II (margin sphere extended below the intersegmental plane but did not involve main subsegmental structures of the basal segments), S6-III (margin sphere extended below the intersegmental plane and involved main subsegmental structures of the basal segments), and S6-IV (margin sphere involved main trunks of the lower lobe). Surgical methods were categorized as S6 segmentectomy (S6-Seg; including isolated and extended S6 segmentectomy) or combined S6 subsegmentectomy (S6-Comb; combined resection of S6 or its subsegments plus adjacent subsegments, such as resection of S6+8a or S6b+8a). The primary endpoint was recurrence-free survival (RFS). Counterfactual mediation analysis was conducted to assess the mediating role of margin distance. The 5-year RFS rates were 96.9% for S6-I, 95.3% for S6-II, 81.5% for S6-III, and 76.6% for S6-IV (log-rank P<0.001). In multivariable analysisadjusted for age, consolidation-to-tumor ratio (CTR), and tumor size, spatial classification was independently associated with RFS [S6-III vs. S6-I: hazard ratio (HR) =5.30, P<0.001; S6-IV vs. S6-I: HR =5.11, P<0.001]. Counterfactual mediation analysis demonstrated that the association between spatial classification and RFS was largely mediated by margin distance [proportion mediated (PM), 84.0% and 92.0% for S6-III vs. S6-I and S6-IV vs. S6-I, respectively]. In the S6-III subgroup, S6-Comb was associated with superior RFS compared with S6-Seg [HR =0.23, 95% confidence interval (CI): 0.07-0.78, P=0.02], an effect partly mediated by margin distance. In the S6-IV subgroup, surgical method was not associated with RFS. The spatial classification system effectively stratifies recurrence risk in S6 NSCLC. Its association with recurrence is largely mediated by surgical margin distance, but its primary strength lies in preoperative risk prediction. We propose a preliminary, anatomy-guided hypothesis-generating algorithm: S6-Seg for S6-I and S6-II tumors, S6-Comb for S6-III tumors, and consideration of lobectomy for S6-IV tumors,which requires validation in prospective studies.
SN - 2218-6751
SN - 2226-4477
ER -