Prognostic value of a three-dimensional spatial classification system for clinical T1a–bN0 non-small cell lung cancer in the superior segment
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: 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 (S 6 ). We hypothesized that this was attributable to the unique spatial location of S 6 tumors and the difficulty in achieving adequate surgical margins. Therefore, we developed a three-dimensional (3D) spatial classification system for S 6 tumors and investigated its prognostic value. Methods: This retrospective cohort study included 916 patients with clinical T1a–bN0 S 6 NSCLC who underwent thoracoscopic segmentectomy from August 2015 to April 2023. Tumors were classified into four groups (S 6 -I to S 6 -IV) based on the relationship between a simulated 2-cm margin sphere and adjacent anatomical structures: S 6 -I (margin sphere located above the intersegmental plane), S 6 -II (margin sphere extended below the intersegmental plane but did not involve main subsegmental structures of the basal segments), S 6 -III (margin sphere extended below the intersegmental plane and involved main subsegmental structures of the basal segments), and S 6 -IV (margin sphere involved main trunks of the lower lobe). Surgical methods were categorized as S 6 segmentectomy (S 6 -Seg; including isolated and extended S 6 segmentectomy) or combined S 6 subsegmentectomy (S 6 -Comb; combined resection of S 6 or its subsegments plus adjacent subsegments, such as resection of S 6+8a or S 6b+8a ). The primary endpoint was recurrence-free survival (RFS). Counterfactual mediation analysis was conducted to assess the mediating role of margin distance. Results: The 5-year RFS rates were 96.9% for S 6 -I, 95.3% for S 6 -II, 81.5% for S 6 -III, and 76.6% for S 6 -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 [S 6 -III vs. S 6 -I: hazard ratio (HR) =5.30, P<0.001; S 6 -IV vs. S 6 -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 S 6 -III vs. S 6 -I and S 6 -IV vs. S 6 -I, respectively]. In the S 6 -III subgroup, S 6 -Comb was associated with superior RFS compared with S 6 -Seg [HR =0.23, 95% confidence interval (CI): 0.07–0.78, P=0.02], an effect partly mediated by margin distance. In the S 6 -IV subgroup, surgical method was not associated with RFS. Conclusions: The spatial classification system effectively stratifies recurrence risk in S 6 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: S 6 -Seg for S 6 -I and S 6 -II tumors, S 6 -Comb for S 6 -III tumors, and consideration of lobectomy for S 6 -IV tumors,which requires validation in prospective studies.
Institution: Jiangsu Province Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223890122