The utility of video-assisted thoracic surgery in vein-first lobectomy for lung cancer with consideration of circulating tumor cells (CTCs): a narrative review
Noriyoshi Sawabata
, Nagisa Hashimoto
Contributions: (I) Conception and design: N Sawabata; (II) Administrative support: N Sawabata; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.
Background and Objective: The vein-first surgical approach in lobectomy for non-small cell lung cancer (NSCLC), which involves ligating the pulmonary vein before the artery and bronchus, is hypothesized to reduce the dissemination of circulating tumor cells (CTCs) during surgery. This review explores the utility of video-assisted thoracic surgery (VATS) for this technique, focusing on its impact on CTCs and clinical outcomes.
Methods: A literature review was conducted using PubMed, Scopus, and Google Scholar for studies published up to June 2025. The search included clinical trials, meta-analyses, and prospective/retrospective cohort studies examining the impact of vein-first VATS lobectomy on CTCs and patient outcomes.
Key Content and Findings: The vein-first approach may reduce intraoperative CTC dissemination. Some studies, including meta-analyses, suggest that this technique is associated with improved disease-free survival (DFS) and overall survival (OS) compared to the artery-first approach, without increasing operative time, blood loss, or postoperative complications. The proposed mechanisms include minimizing tumor manipulation prior to venous control and reducing intratumoral pressure. However, the existing evidence is largely based on non-randomized studies with methodological limitations.
Conclusions: VATS combined with a vein-first approach is a technically feasible strategy that may offer oncologic benefits by reducing CTC spread. However, due to the limitations of the current evidence, large-scale, prospective randomized trials are crucial to validate these findings and to define the patient populations that would benefit most from this technique.
Keywords: Video-assisted thoracic surgery (VATS); vein-first lobectomy; lung cancer; circulating tumor cells (CTCs); surgical technique
Received: 03 May 2025; Accepted: 09 September 2025; Published online: 24 September 2025.
doi: 10.21037/vats-25-15
Introduction
Surgical resection remains the cornerstone of curative-intent treatment for early-stage non-small cell lung cancer (NSCLC). Video-assisted thoracic surgery (VATS) has become the standard of care for lobectomy, offering patients reduced postoperative pain, shorter hospital stays, and faster recovery compared to traditional open thoracotomy (1,2).
Beyond the benefits of a minimally invasive approach, attention has shifted towards refining surgical techniques to improve long-term oncologic outcomes. One such refinement is the “vein-first” approach to pulmonary lobectomy, where the pulmonary vein is ligated before the pulmonary artery and bronchus. The primary rationale for this technique is to minimize the risk of disseminating circulating tumor cells (CTCs) during surgical manipulation of the tumor-bearing lobe. CTCs, which are cancer cells shed from a primary tumor into the bloodstream, are considered a key precursor to metastasis (3,4) and their presence is associated with a poorer prognosis in NSCLC patients (5).
While the vein-first concept is biologically plausible, its clinical benefit remains a subject of debate. Several studies have compared the vein-first and artery-first techniques, but their findings are varied and often limited by study design. To date, there is no recent narrative review that synthesizes the current evidence on vein-first VATS lobectomy with a specific focus on CTCs as a mechanistic link to survival outcomes, nor one that critically discusses the technical and research-related nuances.
This review aims to address this gap by synthesizing the current literature on the utility of vein-first VATS lobectomy for lung cancer. We will evaluate its impact on CTC dynamics and patient survival, discuss the proposed biological mechanisms, critically appraise the quality of the available evidence, and outline future directions for research. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-25-15/rc).
Methods
A literature review was conducted to identify relevant studies published up to June 2025 using the PubMed, Scopus, and Google Scholar databases. The search strategy included a combination of MeSH terms and free-text words such as “vein-first”, “artery-first”, “lobectomy”, “lung cancer”, “NSCLC”, “VATS”, “thoracoscopic”, and “circulating tumor cells”.
Inclusion criteria were: (I) clinical trials, meta-analyses, prospective or retrospective cohort studies; (II) studies comparing vein-first versus artery-first lobectomy; (III) studies reporting on at least one of the following outcomes: CTC counts, overall survival (OS), disease-free survival (DFS), recurrence, or operative outcomes; and (IV) articles published in English. Case reports, editorials, letters, and reviews that did not provide original data were excluded. The selection of articles was performed independently by two authors, with discrepancies resolved by consensus. The detailed search strategy is summarized in Table 1.
Table 1
| Items | Specification |
|---|---|
| Date of search | The initial search conducted on April 28, 2025, and a final updated search on June 20, 2025 |
| Databases and other sources searched | Electronic databases searched were PubMed, Scopus, and Google Scholar. Additionally, the reference lists of key review articles and included studies were manually screened to identify any further relevant publications |
| Search terms used | A combination of MeSH and free-text keywords was utilized. The core search string was structured as follows: (“vein-first” OR “venous-first” OR “vein ligation first”) AND (“artery-first”) AND (“lobectomy” OR “pulmonary resection”) AND (“lung cancer” OR “non-small cell lung cancer” OR “NSCLC”) AND (“VATS” OR “video-assisted thoracic surgery” OR “thoracoscopic”) AND (“circulating tumor cells” OR “CTCs”) |
| Timeframe | From database inception to June 2025 |
| Inclusion and exclusion criteria | Inclusion criteria |
| • Study type: randomized clinical trials, meta-analyses, prospective cohort studies, and retrospective cohort studies | |
| • Population: patients undergoing VATS lobectomy for NSCLC | |
| • Intervention & comparison: direct comparison between a vein-first and an artery-first surgical technique | |
| • Outcomes: studies reporting on at least one of the following: CTC counts, survival rates (OS, DFS), recurrence rates, or detailed perioperative outcomes | |
| Exclusion criteria | |
| • Publication type: case reports, editorials, letters to the editor, and narrative reviews without original data analysis | |
| • Language: studies not published in the English language | |
| • Content: studies lacking sufficient data for the outcomes of interest or not directly comparing the two specified surgical approaches | |
| Selection process | Two authors (N.S. and N.H.) independently screened the titles and abstracts of all retrieved articles to identify potentially eligible studies. The full text of these selected articles was then thoroughly reviewed to confirm eligibility based on the predefined inclusion and exclusion criteria. Any disagreements during the selection process were resolved through discussion and consensus with a third author |
CTC, circulating tumor cell; DFS, disease-free survival; MeSH, Medical Subject Headings; NSCLC, non-small cell lung cancer; OS, overall survival; VATS, video-assisted thoracic surgery.
Results
Comparative outcomes of vein-first vs. artery-first lobectomy
The literature comparing vein-first and artery-first VATS lobectomy reports on three main categories of outcomes: survival rates, CTC dynamics, and perioperative results.
Survival and recurrence
A meta-analysis by Zhao et al. [2021], which included seven studies, found that the vein-first approach was associated with significantly better DFS [risk ratio (RR) 0.52] and 5-year OS (RR 0.60) compared to the artery-first approach (6). However, the same review noted no significant difference in the risk of local recurrence or distant metastasis (6). A randomized clinical trial (RCT) by Wei et al. [2019] also reported a trend towards improved survival, although the primary endpoint was CTCs (7).
CTCs
The impact on intraoperative CTC dissemination is a key focus. The RCT by Wei et al. [2019] demonstrated that patients undergoing vein-first lobectomy had significantly lower postoperative levels of folate receptor-positive CTCs compared to those in the artery-first group (7). This provides direct evidence supporting the hypothesis that early venous ligation reduces tumor cell shedding. However, a prospective study by Sawabata et al. [2021] found no significant difference in the detection of clustered CTCs between the groups, although they did find that the postoperative detection of CTC clusters was a predictor of recurrence (8).
Operative and postoperative outcomes
Across multiple studies, including retrospective cohorts and meta-analyses, the vein-first approach has been shown to be as safe as the artery-first technique. Operative time, intraoperative blood loss, the incidence of postoperative complications, and the length of hospital stay were consistently found to be comparable between the two groups (6-9). This indicates that the vein-first technique does not add significant surgical complexity or risk in experienced hands. A summary of reported outcomes is presented in Table 2.
Table 2
| Outcome | Vein-first approach | Artery-first approach | References |
|---|---|---|---|
| Operative time (minutes) | Comparable/no significant difference reported | Standard | (6-9) |
| Intraoperative blood loss (mL) | Comparable/no significant difference reported | Standard | (6-9) |
| Postoperative complications (%) | Comparable rates reported | Standard | (6-8) |
| Length of hospital stay (days) | Comparable/no significant difference reported | Standard | (6-9) |
| Postoperative CTC detection/levels | Significantly lower postoperative levels reported in RCT | Standard/baseline | (6-8) |
| DFS | Improved (RR 0.52 in a meta-analysis) | Standard | (6) |
| OS | Improved (RR 0.60 in a meta-analysis) | Standard | (6) |
| Recurrence/metastasis | No significant difference reported in some studies | Standard | (6,7) |
CTC, circulating tumor cell; DFS, disease-free survival; OS, overall survival; RCT, randomized clinical trial; RR, risk ratio.
Mechanisms of reduced CTC dissemination
Several plausible mechanisms have been proposed to explain how the vein-first approach may reduce CTC dissemination during surgery (Figure 1).
- Minimization of tumor manipulation: this is the central hypothesis. By ligating the venous outflow tract first, subsequent manipulation of the lung lobe during dissection of the artery and bronchus is less likely to push tumor cells into the systemic circulation (7,9). Physical handling of the tumor is a known factor that can increase CTC levels.
- Reduction of intratumoral vascular pressure: securing the primary venous outflow before extensive tumor manipulation is thought to prevent pressure spikes that could force cells into circulation (9,10). The concept is supported by studies in colorectal cancer surgery showing that early vein ligation can contain cells within the specimen (10).
- Improved hemodynamic stability: some studies have noted that the vein-first approach may be associated with more stable intraoperative hemodynamics and less blood loss. Stable blood pressure and minimized bleeding could help maintain vascular integrity and reduce the chances of tumor cells escaping into circulation through damaged vessels (6,7).
A summary of these mechanisms is presented in Table 3.
Table 3
| Potential mechanism | Description | Supporting evidence |
|---|---|---|
| Minimization of tumor manipulation | Ligating the pulmonary vein before extensive manipulation of the tumor-bearing lobe serves as a primary barrier, preventing the mechanical extrusion of tumor cells into the systemic circulation | This is the central hypothesis, supported by RCT data showing lower postoperative CTC levels and analyses on surgical manipulation dynamics (7,9) |
| Reduction of intratumoral pressure | By securing the main venous outflow first, the pressure gradient that facilitates the passive shedding of tumor cells from the tumor vasculature into the bloodstream may be reduced | This concept is supported by research in other surgical fields (e.g., colorectal surgery) showing that early vein ligation can decrease intravascular pressure within the tumor (9,10) |
| Improved hemodynamic stability | The vein-first technique may be associated with more stable intraoperative hemodynamics and reduced bleeding. This stability helps maintain vascular integrity, minimizing potential escape routes for tumor cells | Some studies have reported more stable blood pressure and less blood loss in the vein-first group, suggesting this as an additional, indirect benefit (6,7) |
CTC, circulating tumor cell; RCT, randomized clinical trial.
Discussion
This review synthesizes the evidence for the vein-first approach in VATS lobectomy, focusing on its role in mitigating CTC spread. While the technique is oncologically appealing and supported by some favorable data, a critical appraisal reveals significant limitations in the current body of literature that warrant a cautious interpretation of its benefits.
Critical appraisal of current evidence
A major limitation of the existing research is the predominance of retrospective, non-randomized studies. These are susceptible to selection bias, where surgeons may preferentially choose the vein-first technique for smaller, more peripheral tumors that are technically less demanding (3,11-14). Although some studies used propensity score matching to mitigate this (9,15), residual confounding is likely. The few RCTs conducted were often small and may lack the statistical power to definitively conclude on survival differences. Furthermore, there is significant heterogeneity across studies in terms of patient populations, tumor stages, and surgical experience, making direct comparisons challenging (3,9,11-14).
Technical challenges and opposing views
The vein-first approach is not without its challenges and is not universally accepted. Anatomically, it can be technically demanding, particularly for right upper lobe tumors (15-17) or in the presence of bulky hilar lymphadenopathy (18-21). Such difficulties could prolong operative time or increase the risk of vascular injury. Moreover, not all studies support its superiority. A recent study on robotic-assisted lobectomy found no significant differences in survival or recurrence between vein-first and artery-first groups, suggesting the surgical platform itself may influence outcomes (11). This highlights that the benefits may not be universal and could depend on patient selection, tumor characteristics (e.g., central vs. peripheral), and surgical platform.
The role and limitations of CTCs
Our review highlights CTCs as a key mechanistic link, yet the clinical utility of CTC detection itself is still evolving. There is no single standardized method for CTC isolation and analysis, leading to variability in detection rates and counts across studies (21-23). While the presence of CTCs is generally a poor prognostic marker, it is not yet established whether surgically-induced transient increases in CTCs have the same clinical implications as pre-existing CTC levels (24,25). More research is needed to validate CTCs as a surrogate endpoint for long-term survival in surgical trials.
Implications for practice and future research
Given the current evidence, advocating for the routine adoption of the vein-first technique for all VATS lobectomies would be premature. However, it represents a safe and feasible option that may confer a benefit in select patients. The decision should be left to the surgeon’s discretion, based on tumor anatomy and their technical expertise.
The most pressing need is for a large-scale, multicenter RCT. Such a trial should stratify patients by tumor location and size, use standardized CTC detection methods, and be adequately powered to assess long-term DFS and OS. Future research should also focus on optimizing surgical techniques—whether VATS or robotic-assisted thoracic surgery (RATS)—to minimize all forms of tumor handling, with CTC dynamics serving as a valuable biological endpoint.
Conclusions
The vein-first approach in VATS lobectomy is a promising technique founded on a strong biological rationale to reduce the intraoperative dissemination of tumor cells. Existing evidence suggests it may improve long-term survival without compromising surgical safety. However, these findings are derived primarily from methodologically limited studies. Until definitive evidence from large-scale randomized trials becomes available, the vein-first technique should be considered a valuable tool in the thoracic surgeon’s armamentarium, to be applied based on individualized anatomical and clinical judgment.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-25-15/rc
Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-25-15/prf
Funding: None.
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-25-15/coif). N.S. serves as an unpaid editorial board member of Video-Assisted Thoracic Surgery from March 2025 to February 2027. The other author has 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.
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/.
References
- Yan TD, Black D, Bannon PG, et al. Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer. J Clin Oncol 2009;27:2553-62. [Crossref] [PubMed]
- Cao C, Manganas C, Ang SC, et al. Video-assisted thoracic surgery versus open thoracotomy for non-small cell lung cancer: a meta-analysis of propensity score-matched patients. Interact Cardiovasc Thorac Surg 2013;16:244-9. [Crossref] [PubMed]
- Song J, Ye X, Peng Q, et al. Circulating Tumor cells and multiple indicators combined to identify the risk of poorer prognosis in patients with resected non-small cell lung cancer. BMC Cancer 2024;24:1491. [Crossref] [PubMed]
- Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781-91. [Crossref] [PubMed]
- Xu Y, Ren X, Jiang T, et al. Circulating tumor cells (CTCs) and hTERT gene expression in CTCs for radiotherapy effect with lung cancer. BMC Cancer 2023;23:475. [Crossref] [PubMed]
- Zhao T, Zhang C, Zhao C, et al. Vein-first versus artery-first ligation procedure for lung cancer surgery: An updated review. J Cardiothorac Surg 2021;16:272. [Crossref] [PubMed]
- Wei S, Guo C, He J, et al. Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non-Small Cell Lung Cancer: A Randomized Clinical Trial and Registry-Based Propensity Score Matching Analysis. JAMA Surg 2019;154:e190972. [Crossref] [PubMed]
- Sawabata N, Nakane S, Yoshikawa D, et al. Vein-first Lobectomy for Lung Cancer Assessed According to the Status of Clustered Circulating Tumour Cells. Cancer Diagn Progn 2021;1:443-50. [Crossref] [PubMed]
- Demicheli R, Fornili M, Ambrogi F, et al. Recurrence dynamics for non-small-cell lung cancer: effect of surgery on the development of metastases. J Thorac Oncol 2012;7:723-30. [Crossref] [PubMed]
- Hayashi N, Egami H, Kai M, et al. No-touch isolation technique reduces intraoperative shedding of tumor cells into the portal vein during resection of colorectal cancer. Surgery 1999;125:369-74.
- Singh G, Abraham PJ, Xie R, et al. Vein-first vs. artery-first robotic lobectomy outcomes in non-small cell lung cancer. J Thorac Dis 2024;16:368-78. [Crossref] [PubMed]
- Minnich DJ, Bryant AS, Ashley DH, et al. Inflow and outflow occlusion technique of the pulmonary artery and veins for the technically difficult left upper lobectomy. Eur J Cardiothorac Surg 2012;41:353-6. [Crossref] [PubMed]
- Sumitomo R, Fukui T, Marumo S, et al. Effects of vessel interruption sequence during thoracoscopic lobectomy for non-small cell lung cancer. Gen Thorac Cardiovasc Surg 2018;66:464-70. [Crossref] [PubMed]
- Shiiya H, Ujiie H, Chiba R, et al. Impact of pulmonary vein-first ligation during lobectomy on the postoperative survival and recurrence rates in patients with non-small cell lung cancer: a multicenter propensity score-matched study. Surg Today 2024;54:1369-78. [Crossref] [PubMed]
- Xiang Z, Feng N, Wu B, et al. The influence of different sequences of vessel ligation on long-term survival during video-assisted thoracoscopic lobectomy for non-small cell lung cancer: A matched cohort study. Medicine (Baltimore) 2023;102:e35619. [Crossref] [PubMed]
- Lavoie J, Burrows FA, Hansen DD. Video-assisted thoracoscopic surgery for the treatment of congenital cardiac defects in the pediatric population. Anesth Analg 1996;82:563-7. [Crossref] [PubMed]
- Lavoie J, Burrows FA, Hansen DD. Video-assisted thoracoscopic surgery for the treatment of congenital cardiac defects in the pediatric population. Anesth Analg 1996;82:563-7. [Crossref] [PubMed]
- Naruke T, Tsuchiya R, Kondo H, et al. Lymph node sampling in lung cancer: how should it be done? Eur J Cardiothorac Surg 1999;16:S17-24. [Crossref] [PubMed]
- Lewis RJ. Simultaneously stapled lobectomy: a safe technique for video-assisted thoracic surgery. J Thorac Cardiovasc Surg 1995;109:619-25. [Crossref] [PubMed]
- Kirby TJ, Mack MJ, Landreneau RJ, et al. Lobectomy--video-assisted thoracic surgery versus muscle-sparing thoracotomy. A randomized trial. J Thorac Cardiovasc Surg 1995;109:997-1001; discussion 1001-2. [Crossref] [PubMed]
- Sugi K, Kaneda Y, Esato K. Video-assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer. World J Surg 2000;24:27-30; discussion 30-1. [Crossref] [PubMed]
- Chen L, He J, Liang H, et al. A dual-mode microfluidic chip embedded with photoelectrochemical sensing and fluorescence imaging for phenotypic analysis of tumor cells. Talanta 2025;295:128275. [Crossref] [PubMed]
- Lin Q, Chen X, Hong Y, et al. Microfluidic chip coupled with photoelectrochemical/fluorescence dual-modal sensing system for the efficient enrichment and detection of circulating tumor cells. Talanta 2025; Epub ahead of print. [Crossref]
- Cieslik SA, Zafra AG, Driemel C, et al. Phenotypic diversity of CTCs and tdEVs in liquid biopsies of tumour-draining veins is linked to poor prognosis in colorectal cancer. J Exp Clin Cancer Res 2025;44:9. [Crossref] [PubMed]
- Mastronicola R, Kayser E, Le Roux P, et al. Study of the survival of patients with head and neck cancer in relation to Circulating Tumor Cells (CTCs). PLoS One 2025;20:e0320485. [Crossref] [PubMed]
Cite this article as: Sawabata N, Hashimoto N. The utility of video-assisted thoracic surgery in vein-first lobectomy for lung cancer with consideration of circulating tumor cells (CTCs): a narrative review. Video-assist Thorac Surg 2025;10:26.
