The Sequence of Vessel Ligation during Lobectomy Affects Survival in Spread Through Air Spaces (STAS)-Positive Stage I Lung Adenocarcinoma

D. Chen¹, X. Xu², Y. Chen^2
1Zhongshan Hospital of Fudan University, Shanghai, Shanghai ²Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu

Purpose: We aimed to investigate the impact of the sequence of vessel ligation during lobectomy on spread through air spaces (STAS)-positive stage I lung adenocarcinoma by analyzing the number of circulating tumor cells (CTCs) in pre- and postoperative peripheral blood.

Methods: A retrospective patient cohort from 2014 to 2018 was included in this study, in which the effect of the sequence of intraoperative vessel ligation during lobectomy was investigated with propensity-score matching (PSM) performed. Synchronously, a prospective cohort comprised of 124 stage I patients with lung adenocarcinoma undergoing lobectomy during 2022 was enrolled, whose peripheral blood samples were collected for counting CTCs. Changes in peripheral CTCs were compared between artery-first (A-first) and vein-first (V-first) groups.

Results: After PSM, a total of 506 patients undergoing lobectomy were included in the retrospective cohort, among whom presence of STAS was identified in 208 patients (41.1%). In this cohort, multivariate analysis revealed that the A-first technique was associated with unfavorable overall survival (OS) and recurrence-free survival (RFS) in both stage IA and IB STAS-positive disease. However, the A-first technique was not an independent predictor of worse OS and RFS compared with the V-first one in stage IA and IB STAS-negative patients. Subgroup analysis of STAS+ stage IB disease further suggested that the V-first technique was associated with better 5-year OS and RFS than the A-first one in patients who did not receive adjuvant chemotherapy (ACT). However, the ligation-associated survival advantage was not evident in patients to whom ACT was administered. In the prospective cohort, an incremental change in CTCs was observed in 43 of 66 patients (65.2%) in the A-first group and 22 of 58 (37.9%) in the V-first group (P < 0.01) after surgery.

Conclusion: Early ligation of pulmonary veins might prevent CTCs from spreading into the circulation and therefore improve survival in stage I STAS-positive lung ADC. Administration of ACT might be considered for stage IB lung ADC undergoing A-first lobectomy once presence of STAS was identified in permanent sections.

Identify the source of the funding for this research project: None