Real-world perioperative and long-term oncologic outcomes after standardized thoracoscopy without access incision (TWAI) major pulmonary resections for non-small cell lung cancer: a retrospective cohort of more than 2,000 patients

Introduction

Minimally invasive thoracic surgery has undergone major evolution over the past decades, establishing video-assisted thoracoscopic surgery (VATS) as the standard approach for early-stage non-small cell lung cancer (NSCLC). Compared with thoracotomy, VATS lobectomy is associated with less postoperative pain, lower analgesic requirements, and shorter hospital stay (1). The multicenter VIOLET trial (2) and subsequent meta-analyses (3) confirmed the safety, effectiveness, and cost-efficiency of this approach.

Lobectomy has long been considered the reference operation for stage I NSCLC, particularly for larger or biologically aggressive tumors. However, segmentectomies, have progressively gained acceptance as curative options for small, peripheral lesions. This paradigm shift has been consolidated in the May 2024 update of the National Comprehensive Cancer Network guidelines (4), which now recognise segmentectomy as a standard treatment in selected cases. The evidence stems mainly from two phase III randomized trials. The Japanese JCOG 0802/WJOG 4607L trial (5) demonstrated improved overall survival (OS) after segmentectomy for clinical T1a–b NSCLC, despite a slightly higher local recurrence rate, while the CALGB 140503 study (6,7) reported no significant differences in OS or recurrence between lobar and sublobar resections.

These data have redefined surgical indications worldwide. In Japan, segmentectomy now accounts for nearly half of anatomical resections for stage I NSCLC, whereas its adoption in Western countries remains heterogeneous, largely dependent on institutional experience and availability of high-precision imaging. Although randomized trials set the foundation for this change, their strict inclusion criteria limit extrapolation to everyday practice. Demonstrating comparable outcomes in a large, unselected population is therefore crucial to validate the oncologic safety of segmentectomy in the real world. Initial scepticism toward VATS for major pulmonary resections, primarily related to oncologic adequacy, has since been addressed. Major resections were defined as lobectomy, bilobectomy, pneumonectomy, and segmentectomy; wedge resections were excluded. The American College of Chest Physicians now recommends thoracoscopic resection as the preferred approach for stage I NSCLC (8). Surgeons performing thoracoscopy without access incision (TWAI) lobectomy must nonetheless maintain oncologic rigor, with complete lymph-node dissection and adequate margins, to ensure equivalence in long-term outcomes (9). Our institution implemented its thoracoscopic program in 1994 and adopted a standardized fissure-based, closed-chest technique for stage I NSCLC in 2007 (10). Earlier analyses described perioperative outcomes, nodal dissection quality, and 5-year survival in an initial cohort of 648 patients (11,12). The present study extends this experience to more than 2,000 prospectively collected cases, aiming to assess the long-term oncologic results of TWAI lobectomy and segmentectomy performed with consistent high-quality standards. Beyond perioperative safety, it seeks to document how the systematic use of complete thoracoscopy has accompanied, the global shift toward segmentectomies as a cornerstone of curative surgery for early-stage NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-62/rc).

Methods

Study design and database

All data were prospectively collected in the institutional thoracic surgery database (Institut Mutualiste Montsouris, Paris). The registry includes all thoracoscopic procedures on an intention-to-treat basis, recording intraoperative events and conversions to thoracotomy. Postoperative staging followed the 8th edition of the tumor-node-metastasis (TNM) classification (13). Survival endpoints were defined as follows: OS from surgery to death or last follow-up; disease-free survival (DFS) from surgery to recurrence or death. In-hospital mortality was defined as death within 30 days or during the initial hospitalization; 90-day outcomes were also evaluated.

Postoperative follow-up was standardised and included clinical assessment and chest computed tomography (CT) at 3, 6, 9, and 12 months after surgery, then every 6 months for the following 2 years, and annually thereafter for 2 additional years. Additional medical consultations were performed in the event of new or concerning symptoms. Missing outcome data were documented; no patients were lost to follow-up in the survival cohort.

Patient population

For perioperative analysis, all TWAI major pulmonary resections performed at the Institute Mutualiste Montsouris between January 2007 and July 2023 were included. Early technical development phase [1994–2006] and robotic-assisted procedures (~300) were excluded. The technical development phase corresponded to the thoracoscopic approach, during which the technique was not yet standardised in terms of surgeon positioning, port placement, and instrumentation; from 2007 onward, a uniform and standardised technique was adopted by all surgeons in the department.

Demographic, clinical, and pathological data were collected prospectively.

Preoperative work-up included thoracic CT, fluorine-18 fluorodeoxyglucose positron emission tomography-CT, and brain magnetic resonance imaging (or CT if contraindicated). Endobronchial ultrasound (EBUS) was used for mediastinal and hilar staging in cases of suspected nodal disease; negative EBUS with persistent suspicion led to mediastinoscopy.

Before 2021, lobectomy was performed for all localized or locally advanced tumors within a multimodal treatment strategy. Segmentectomy was considered a compromise procedure and was therefore reserved for patients deemed unable to tolerate lobectomy due to impaired functional status. Since 2021, the indications for segmentectomy have expanded to include intentional resections for peripheral tumors <2 cm with a consolidation-to-tumor ratio (CTR) >0.5, as well as for patients with impaired pulmonary function, prior lung resections, or multiple synchronous lesions, in accordance with the results of the JCOG0802/WJOG4607L and CALGB 140503 trials. Conversely, lobectomy was performed for central tumors, tumors ≥2 cm, suspected or confirmed nodal involvement, or when intraoperative frozen section analysis revealed inadequate margins after a planned segmentectomy, prompting conversion. Wedge resection was not included as an oncologic option in this cohort.

Postoperative management was conducted according to contemporary multidisciplinary tumor board recommendations. Adjuvant systemic therapy was administered in node-positive patients in accordance with prevailing guidelines. In cases of recurrence during follow-up, systemic treatment was introduced when indicated.

Perioperative management

Enhanced recovery after surgery (ERAS) principles were progressively introduced, following European Society of Thoracic Surgeons recommendations (14). The program included multidisciplinary preoperative assessment (respiratory physiotherapy, nutrition, geriatric evaluation when indicated), early mobilization, and early removal of drains. Arrhythmia prophylaxis with preoperative amiodarone was implemented from 2018 (15), and venous thromboembolism prevention used daily low-molecular-weight heparin until full ambulation. A formalized ERAS pathway was established in 2023 with dedicated nursing coordination; given this timing, its direct impact on outcomes was minimal for the present cohort.

Operative technique

All operations were performed using a standardized fissure-first, closed-chest TWAI approach derived from the posterior technique described by Richards et al. (16). Procedures were done entirely under monitor vision with a high-definition deflectable endoscope and three to four ports, without utility incision.

Radical hilar and mediastinal lymph node dissection was systematic. Right-sided dissections included stations 2, 4, and 7–10; left-sided dissections included 5–10. Interlobar and intersegmental nodes (stations 12–13) were routinely cleared, and frozen-section analysis verified N1 nodes and intersegmental margins. If inadequate margins or tumor infiltration were detected, conversion to lobectomy was performed. Limited or omitted nodal dissection was reserved for patients aged >80 years or unfit for adjuvant therapy.

Segmentectomy planning employed three-dimensional (3D) reconstruction software (Visible Patient^®) to delineate segments and ensure adequate resection margins, defined as at least twice the tumor diameter. Histologic assessment verified the intersegmental plane (ISP) margin-to-tumor ratio (ISP ≥1 considered adequate). The ISP margin ratio was measured on the inflated and fixed lung specimen, after removal of the staple line (approximately 5 mm). The shortest distance between the tumor and the nearest ISP was measured and then normalised to the tumor diameter to obtain the ISP margin ratio.

Chest tubes were removed when drainage was <400 mL/day without significant air leak (<20 mL/min on the Thopaz^® system).

Statistical analysis

Analyses were performed using IBM SPSS Statistics 25 (IBM Corp.) and Stata (StataCorp). Categorical variables were summarized as counts and percentages; continuous variables as medians [interquartile range (IQR)]. Survival curves were generated by Kaplan-Meier and compared using log-rank tests. Univariate Cox proportional hazards models identified factors associated with OS and DFS; Multivariable modelling was not performed due to insufficient events in key subgroups. Proportional hazard assumptions were verified by log-log plots. Group comparisons used chi-square or Fisher’s exact tests for categorical data and Student’s t-test for continuous data. Significance was defined as P<0.05.

Ethics consideration

The institutional database was declared to the French Data Protection Authority (CNIL; No. 1682873v0). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The protocol was approved by the ethics committee of the French Society for Thoracic and Cardiovascular Surgery (No. CERC-CTCV-2024-07-08_35494), and individual consent was waived according to French regulations.

Results

Patient characteristics and type of resection

Between 1994 and 2023, a total of 2,711 TWAI procedures were recorded, including 2,425 performed with curative intent for NSCLC. After exclusion of early non-standardised cases performed before 2007, 2,232 major pulmonary resections by VATS were eligible for analysis. After excluding 108 patients with incomplete outcome data who were not eligible for time-to-event analyses, there was no loss to follow-up in the survival cohort. A total of 2,124 patients constituted the perioperatives cohort. Among them, 1,889 patients with confirmed NSCLC treated with curative intent were eligible for survival analysis (Figure S1).

Baseline characteristics

Baseline characteristics are summarised in Table 1, based on 2,124-patient cohort.

Median patient age was 68 years (IQR: 61–73 years), with an equal sex distribution (52% women). The majority were current or former smokers (76.9%), with preserved pulmonary function [median FEV₁ 88.6% predicted, diffusing capacity for carbon monoxide (DLCO) 73.6%]. Among all resections, 1,319 (62.1%) were lobectomies and 776 (36.5%) segmentectomies, confirming a progressive increase in sublobar resections over the study period. Bilobectomy (0.8%), pneumonectomy (0.1%), and combined lobectomy with segmentectomy (0.5%) were rare. The distribution of lobectomies by lobe is shown in Table 1, reflecting a predominance of right upper lobe resections (39.9%), followed by right lower (19.4%) and left upper lobes (16.3%).

Operative outcomes and complications

Operative and postoperative data are detailed in Table 2, based on 2,124-patient cohort.

Median operative time was 160 minutes (IQR: 125–200 minutes), with median blood loss of 80 mL (IQR: 40–150 mL). Conversion to thoracotomy occurred in 5.4% (n=114) of cases and decreased over time, from 7.8% before 2015 to 4.3% after 2020. Conversion causes included vascular injury (n=41), dense adhesions or fissure fusion (n=36), oncologic concerns (n=9), and technical difficulties such as selective ventilation failure or limited exposure (n=28). Thirty-day mortality was 0.3% (n=7), and 90-day mortality was 1% (n=22). Causes of early death included acute respiratory distress syndrome (n=3), pulmonary embolism (n=1), splenic rupture (n=1), intraoperative cardiac injury (n=1), and systemic embolism after lobar torsion (n=1). Median chest-tube duration was 3 days (IQR: 2–5 days), and hospital stay 5 days (IQR: 4–7 days). Postoperative complications occurred in 32.6% (n=693) of patients, predominantly respiratory (22.3%). The most frequent were prolonged air leak (11.1%), emphysema or pneumothorax (4.9%), and pneumonia (4.1%). Cardiac complications accounted for 2.5% (mainly atrial fibrillation, 2.2%), with lower rates observed after 2018 following systematic amiodarone prophylaxis (15). Other complications (hemorrhagic 1.6%, infectious 1.5%) were uncommon. Only 0.4% of patients required reoperation for bleeding, and 0.28% experienced pulmonary embolism.

Operative outcomes showed low conversion and mortality rates despite the large cohort and broad real-world inclusion.

Pathological and oncological findings

Pathologic results are summarised in Table 3, based on 2,124-patient cohort. NSCLC represented 88.8% (n=1,887) of resections. Two undifferentiated tumors (0.05%) were also identified and included in the survival analysis. Adenocarcinoma was predominant (72.9%, n=1,549), following by squamous cell carcinoma accounted for 11.8% (n=251), Carcinoid tumors for 5.5% (n=116), metastatic lesions for 1.9% (n=41), and benign nodules for 2.7% (n=58). Four nodules (0.2%) could not be localised intraoperatively.

Oncological findings are summarised in Table 4, based on 1,889-patient cohort.

Tumor size

Median tumor size was 2 cm (IQR: 1.5–3.0 cm); 40.2% of lesions measured <2 cm and 33.8% between 2 and 5 cm.

Lymph node dissection

A median of 16 lymph nodes (IQR: 12–22) were harvested. Adequate nodal dissection (≥6 nodes) was achieved in 78.5% (n=1,667), while it was limited (<6 nodes) in 5.2% (n=111) and intentionally omitted in 2.2% (n=47), mainly in elderly or frail patients.

Pathological stage

Upstaging from clinical to pathological stage (above pIB stage) occurred in 11.4% of clinical stage IA and 25.9% of stage IB tumors, due primarily to occult nodal disease (N1: 3.9–6.9%; N2: 4.1–10.7%). Downstaging from IB to IA occurred in 7.7%, reflecting radiologic overestimation.

Pathological nodal involvement

Overall, 116 patients (6.1%) were pN1 and 126 patients (6.7%) were pN2, corresponding to all cases of pathological nodal involvement identified after systematic lymph-node dissection, including 70 patients with skip metastases (N2 without N1 involvement).

Resection status

Microscopic negative parenchymal margins were achieved in 99.9% of cases, with only two R1 resections (0.1%). According to International Association for the Study of Lung Cancer (IASLC) definitions (17), 91.2% (n=1,723) were classified as R0, while 5.1% (n=97) were categorized as R(un), mainly due to intentionally omitted nodal dissection in elderly or frail patients.

These results confirm a high oncologic completeness rate across the entire cohort.

Survival analysis: based on 1,889-patient cohort

Overall survival (OS) and disease-free survival (DFS)

The survival cohort comprised 1,889 patients with histologically confirmed NSCLC and undifferentiated tumor. Median follow-up was 55.6 months (~4.6 years), 5-year OS was 83.0% (95% CI: 81–85%) and DFS 75.7% (95% CI: 74–78%) (Figure 1).

Figure 1 OS (A) and DFS (B) for all TWAI major pulmonary resections. CI, confidence interval; DFS, disease-free survival; OS, overall survival; TWAI, thoracoscopy without access incision.

Comparison of segmentectomy vs. lobectomy

Baseline characteristics were largely comparable between segmentectomy and lobectomy groups, with a slightly higher age in the segmentectomy group (Table S1).

Comparative perioperative outcomes by procedure (segmentectomy and lobectomy) are presented in Table S2.

Detailed analyses of postoperative complications, including distribution by procedure, patient-level burden, and classification by type, are provided in Table S3.

Segmentectomy was associated with higher 5-year OS (86.8% vs. 81.0%, P=0.002) and DFS (81.6% vs. 72.7%, P<0.001) compared with lobectomy (Figure 2A,2B). These differences were no longer significant in clinical stage I disease (OS 88.1% vs. 86.9%, P=0.40; DFS 84.5% vs. 80.1%, P=0.08) (Figure 2C,2D).

Figure 2 Comparison of OS and DFS between segmentectomy and lobectomy, in all cases (A,B) and in stage I disease (C,D). CI, confidence interval; DFS, disease-free survival; OS, overall survival.

When stratified by nodal status, outcomes in node-negative (N0) patients were modest for OS: 87.4% vs. 85.5%, P=0.01, but more significant for DFS: 83.4% vs. 78.1%, P<0.001 (Figure 3A,3B). In node-positive (N⁺) disease, OS 82.4% vs. 65.2%, P=0.02 and DFS 73.6% vs. 52.4%, P<0.001 (Figure 3C,3D).

Figure 3 Comparison of OS and DFS between segmentectomy and lobectomy according to nodal status: N0 (A,B) and N+ (C,D). CI, confidence interval; DFS, disease-free survival; OS, overall survival.

Segmentectomy subgroup and prognostic analyses

Pathological stage

In thoracoscopic segmentectomy, survival correlated closely with pathological stage (Figure 4, A1,A2). Five-year OS and DFS for pIA disease reached 88.8% (95% CI: 85–93%), and 86.1% (95% CI: 81–89%), respectively, decreasing gradually for higher stages but remaining above 70% in pII cases, except in pIIA (33%) (95% CI: 0.9–77%).

Figure 4 Prognostic factors in thoracoscopic segmentectomy: OS (left) and DFS (right) according to pathological stage (A1,A2), lymph-node harvested (B1,B2), intersegmental plane ratio (C1,C2), and tumor size (D1,D2). CI, confidence interval; DFS, disease-free survival; OS, overall survival.

Lymph node dissection

Patients with ≥6 harvested nodes had the best long-term outcomes, with 5-year OS of 88% (95% CI: 84–90%) and DFS of 83.3% (95% CI: 79–86%). While the difference in OS was not statistically significant (HR 0.5, 95% CI: 0.22–1.18, P=0.11), DFS was significantly reduced (HR 0.70, 95% CI: 0.23–0.99, P=0.046).

Patients without lymph-node dissection (N0) had intermediate OS (85.2%) but lower DFS (69.5%).

Limited dissections (<6 nodes) showed a non-significant trend toward worse outcomes (Figure 4, B1,B2).

Margin

Margin adequacy was associated with a consistent trend toward improved survival (OS 93.6% vs. 93.1%, P=0.08 and DFS 88.7% vs. 80.1%; P=0.07) (Figure 4, C1,C2). Although these differences did not reach statistical significance.

Tumor size

Lesions <2 cm had higher 5-year OS (88.6%; 95% CI: 84–91%) and DFS (84.2%) compared with lesions ≥2 cm (OS 80.5%, 95% CI: 71–86%, P=0.01; DFS 74.2%, 95% CI: 64–81%; P=0.003) (Figure 4, D1,D2). Tumor size <2 cm was associated with improved OS and DFS in univariable analysis.

Discussion

This large, single-centre retrospective analysis of a prospectively maintained database confirms that a standardized TWAI fissure-first approach for both lobectomy and segmentectomy achieves excellent long-term oncologic outcomes for early-stage NSCLC, with minimal perioperative morbidity and mortality. The 30- and 90-day mortality rates of 0.3% and 1.0% reflect the maturity and reproducibility of this minimally invasive program. These results consolidate previous evidence demonstrating that thoracoscopic major pulmonary resections are safe, feasible, and oncologically sound when performed by experienced teams (18-21). In our series, low conversion and mortality rates further support the safety and reproducibility of the TWAI approach in a large real-world cohort.

The growing role of segmentectomies

Over the past decade, segmentectomy has shifted from a compromise reserved for frail patients to an intentional, parenchyma-sparing oncologic procedure for small, peripheral NSCLC. This change aligns with the landmark JCOG 0802 (5) and CALGB 140503 (6,7) trials, which demonstrated the non-inferiority of segmentectomy in selected patients. In our experience, this shift also reflects a deliberate institutional policy toward parenchyma-sparing surgery for small, peripheral stage I NSCLC. However, these trials were performed in highly selected populations and under ideal surgical conditions that are rarely replicated in everyday practice. Our real-world cohort suggests that, when performed thoracoscopically with strict adherence to oncologic principles, including adequate margins and systematic lymph-node dissection, segmentectomy was associated with equivalent or higher unadjusted survival compared with lobectomy in selected patients. In our series, Segmentectomy was associated with higher 5-year OS and DFS overall, whereas these differences were no longer statistically significant in clinical stage I disease. Although baseline functional operability appeared comparable (Table S1), residual confounding and indication bias inherent to this observational design may partly account for these differences.

The survival advantage seen for small (<2 cm) tumors highlights its suitability for early-stage disease. As the proportion of incidentally detected small nodules continues to rise, segmentectomy may become the most frequent anatomical resection for stage I NSCLC.

Determinants of oncologic quality

Patients with ≥6 harvested nodes had the best long-term outcomes, with 5-year OS of 88.0% and DFS of 83.3%. Omission of nodal dissection was associated with significantly worse DFS, whereas the difference in OS did not reach statistical significance (Figure 4, B2), suggesting an increased risk of recurrence in the absence of lymph-node dissection. Multivariable modelling was not performed due to an insufficient number of events to ensure reliable adjustment. Although other comparisons did not reach statistical significance, hazard ratios consistently suggested a negative impact of inadequate nodal assessment (Figure 4, B1,B2). This emphasises that the oncologic integrity of segmentectomy relies on the same systematic nodal clearance as lobectomy (22). Similarly, achieving an ISP ≥1 was associated with improved OS and DFS. Although not statistically significant, this consistent trend suggests that adequate segmental margins may confer an oncological benefit, supporting current recommendations of securing at least one tumor diameter of clear margin (23) (Figure 4, C1,C2). Our preoperative 3D planning strategy, targeting a margin twice the tumor diameter, ensures conservative yet safe resections.

In node-positive (N⁺) disease, segmentectomy was associated with better unadjusted OS and DFS than lobectomy. However, this finding should be interpreted with caution given the small subgroup size and the high risk of selection bias and residual confounding. But these results are consistent with the hypothesis that systemic therapy exerts a greater influence on prognosis than resection extent (24). These data raise the hypothesis that immediate completion lobectomy for occult N1 involvement may not always be necessary when adjuvant treatment is planned, provided the initial segmentectomy achieved oncologic margins and thorough nodal evaluation.

Technical and technological considerations

The fissure-first, posterior approach used in our program allows radical lymph-node dissection under TWAI vision while preserving the principles of open surgery. Technological advances, including high-definition imaging, energy devices, and indocyanine-green fluorescence, have facilitated safer identification of segmental planes and vessels. Since 2007, our department has used this method systematically, ensuring procedural consistency across the 2,000-case series. Progressive reductions in conversion rates over time further illustrate the impact of increasing surgical experience and technical refinement within this standardized program.

Robotic-assisted thoracic surgery (RATS) provides additional benefits of articulation, tremor filtration, and 3D visualization (25-27). Although excluded from this analysis for homogeneity, robotics may prove especially advantageous for complex segmentectomies or post-immunochemotherapy resections where fibrosis limits mobility (28). Our institution progressively implemented a robotic program during the study period, and future combined TWAI-RATS experience could help define the optimal minimally invasive strategy.

Comparison with external data

When compared with large national datasets, our outcomes appear favourable. The French EPITHOR registry [2016–2022] reported 5-year OS of 80% for lobectomy and 78% for segmentectomy (29), whereas our series achieved 87% OS and 83% DFS in stage I disease. Differences likely reflect case selection, surgical expertise, and nodal dissection quality. Such results demonstrate the potential for excellent outcomes when segmentectomy is performed within a structured, high-volume, minimally invasive program.

Perspectives: beyond surgery

The management of early-stage and oligometastatic NSCLC is rapidly evolving with new systemic and local treatments. Immunochemotherapy, targeted therapy, and advances in imaging have expanded the spectrum of patients eligible for curative-intent local therapy (30-32). Segmentectomy offers a unique balance between oncologic completeness and parenchymal preservation, making it a cornerstone for integrating surgery with multimodal approaches.

In this context, local ablative therapies, such as stereotactic body radiotherapy and percutaneous or bronchoscopic thermal ablation, represent complementary strategies for patients unsuitable for resection or with multiple lesions. Microwave or radiofrequency ablation, delivered either percutaneously or via navigational bronchoscopy, has shown promising results in terms of local control and safety, particularly for small, peripheral tumors or pulmonary metastases. Early clinical studies suggest that bronchoscopic microwave ablation achieves durable control with minimal morbidity, potentially extending curative treatment to medically inoperable patients (33). Future comparative studies should evaluate these options against anatomical resection in well-defined subgroups.

Emerging tools: circulating tumor DNA (ctDNA) and artificial intelligence (AI)

The integration of molecular and computational technologies is redefining postoperative management. ctDNA can detect minimal residual disease earlier than imaging and could guide adjuvant therapy or intensified surveillance. Persisting ctDNA after surgery is associated with early relapse and poor DFS, suggesting a role for ctDNA-guided adjuvant therapy in future trials (34-36).

AI and machine learning also hold great promise for personalising thoracic oncology. Deep-learning algorithms have already matched or surpassed radiologists in detecting early lung cancer on low-dose CT scans (37,38). AI-based models analysing radiomics and digital pathology can predict recurrence and lymph-node involvement more accurately than conventional histopathology (39-41). Integrating these tools into clinical workflows may help surgeons refine risk stratification, tailor the extent of resection, and individualise follow-up protocols.

Study limitations

This study has several limitations inherent to its design.

Although derived from a prospectively maintained database, survival analyses were retrospective and reflect a single-centre experience. As with all observational surgical series, selection bias cannot be entirely excluded. Segmentectomy was more frequently performed for smaller and peripheral tumors, and surgical indications evolved over time, particularly after the expansion of segmentectomy criteria in 2021. No era-stratified or propensity-score analyses were performed; such approaches may further refine comparisons in future work. Consequently, patients undergoing segmentectomy and lobectomy did not constitute strictly identical populations across the study period. Robotic cases were excluded to preserve technical homogeneity, strengthening internal validity but potentially limiting external generalisability.

The number of oncological events in certain subgroups constrained multivariable modelling. In addition, segmentectomies were not subclassified as simple or complex, and tumor size subcategories within stage I disease were not analysed separately. While further stratified analyses may offer additional refinement, the OS patterns observed remained consistent.

Local recurrence was not assessed as an independent endpoint, as recurrence was captured within DFS parameters. Moreover, adjuvant and post-recurrence systemic therapies were not incorporated into adjusted survival models and may have influenced long-term outcomes, particularly in node-positive disease. However, postoperative management followed standardized multidisciplinary and guideline-based strategies, limiting heterogeneity in systemic treatment exposure. A subset of patients also underwent resection for synchronous or metachronous second primary lung cancers, which may have influenced survival trajectories; this nonetheless reflects real-world oncological practice.

Finally, a direct comparison with 10-year outcomes from randomized trials is currently limited because our cohort has not yet reached a uniform 10-year follow-up and because the most recent long-term JCOG0802 results have not yet been fully peer-reviewed/published at the time of submission. Despite these limitations, the large cohort size, prolonged follow-up, and technical consistency of surgical management provide a meaningful real-world complement to randomized evidence.

Conclusions

This retrospective analysis of a prospectively maintained database of more than 2,000 TWAI major pulmonary resections confirms that a standardized fissure-first approach provides excellent long-term oncologic outcomes for early-stage NSCLC, with very low perioperative mortality and morbidity. When performed under strict oncologic standards, including anatomical resection, systematic lymph-node dissection, and adequate margins, thoracoscopic segmentectomy yields survival equivalent to, and in selected patients superior to, lobectomy.

Segmentectomy should now be regarded as an intentional, parenchyma-sparing operation rather than a compromise for high-risk patients. Its oncologic reliability is particularly clear for node-negative, small (<2 cm) peripheral tumors, where lung preservation translates into improved postoperative function without compromising cure.

In node-positive disease, prognosis appears more dependent on systemic therapy than on the extent of resection, supporting a selective rather than systematic approach to completion lobectomy when adjuvant treatment is planned.

The emergence of complementary local treatments, such as stereotactic body radiotherapy and endobronchial or percutaneous thermal ablation, alongside advances in molecular monitoring (ctDNA) and AI-based risk assessment, will further personalise surgical decision-making.

In this evolving landscape, thoracoscopic segmentectomy stands as a pivotal component of multimodal, precision-guided management for early-stage and downstaged NSCLC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-62/rc

Data Sharing Statement: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-62/dss

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-62/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-62/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 protocol was approved by the ethics committee of the French Society for Thoracic and Cardiovascular Surgery (No. CERC-CTCV-2024-07-08_35494), and individual consent was waived according to French regulations.

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

1. D'Amico TA. VATS lobectomy facilitates the delivery of adjuvant docetaxel-carboplatin chemotherapy in patients with non-small cell lung cancer. J Thorac Dis 2016;8:296-7. [Crossref] [PubMed]
2. Lim E, Harris RA, McKeon HE, et al. Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT. Health Technol Assess 2022;26:1-162. [Crossref] [PubMed]
3. Taioli E, Lee D, Lesser M, et al. Long-term survival in video-assisted thoracoscopic lobectomy vs open lobectomy in lung-cancer patients: a meta-analysis. Eur J Cardiothorac Surg 2013;44:591-7. [Crossref] [PubMed]
4. Riely GJ, Wood DE, Ettinger DS, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2024;22:249-74. [Crossref] [PubMed]
5. Saji H, Okada M, Tsuboi M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet 2022;399:1607-17. [Crossref] [PubMed]
6. Altorki N, Wang X, Kozono D, et al. Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer. N Engl J Med 2023;388:489-98. [Crossref] [PubMed]
7. Altorki N, Wang X, Damman B, et al. Lobectomy, segmentectomy, or wedge resection for peripheral clinical T1aN0 non-small cell lung cancer: A post hoc analysis of CALGB 140503 (Alliance). J Thorac Cardiovasc Surg 2024;167:338-47.e1. Erratum in: J Thorac Cardiovasc Surg 2025;169:1181.
8. Howington J, Blum M, Chang A, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e278S-e313S.
9. Treasure T. Videothoracoscopic resection for lung cancer: moving towards a "standard of care". J Thorac Dis 2016;8:E772-4. [Crossref] [PubMed]
10. Gossot D, Ramos R, Brian E, et al. A totally thoracoscopic approach for pulmonary anatomic segmentectomies. Interact Cardiovasc Thorac Surg 2011;12:529-32. [Crossref] [PubMed]
11. Ramos R, Girard P, Masuet C, et al. Mediastinal lymph node dissection in early-stage non-small cell lung cancer: totally thoracoscopic vs thoracotomy. Eur J Cardiothorac Surg 2012;41:1342-8; discussion 1348. [Crossref] [PubMed]
12. Lutz JA, Seguin‑Givelet A, Grigoroiu M, et al. Oncological results of full thoracoscopic major pulmonary resections for clinical Stage I non-small-cell lung cancer. Eur J Cardiothorac Surg 2019;55:263-70. [Crossref] [PubMed]
13. Lababede O, Meziane MA. The Eighth Edition of TNM Staging of Lung Cancer: Chart and Diagrams. Oncologist 2018;23:844-8.
14. Batchelor TJP, Rasburn NJ, Abdelnour-Berchtold E, et al. Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS). Eur J Cardiothorac Surg 2019;55:91-115. [Crossref] [PubMed]
15. Tisdale JE, Wroblewski HA, Wall DS, et al. A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection. Ann Thorac Surg 2009;88:886-93; discussion 894-5. [Crossref] [PubMed]
16. Richards J, Dunning J, Oparka J, et al. Video-assisted thoracoscopic lobectomy: the Edinburgh posterior approach. Ann Cardiothorac Surg 2012;1:61-9.
17. Rami-Porta R, Wittekind C, Goldstraw P, et al. Complete resection in lung cancer surgery: proposed definition. Lung Cancer 2005;49:25-33. [Crossref] [PubMed]
18. Fournel L, Zaimi R, Grigoroiu M, et al. Totally thoracoscopic major pulmonary resections: an analysis of perioperative complications. Ann Thorac Surg 2014;97:419-24. [Crossref] [PubMed]
19. Mariolo AV, Seguin-Givelet A, Gossot D. Fatal Stroke After Reoperation for Lobar Torsion. Ann Thorac Surg 2020;110:e51-3. [Crossref] [PubMed]
20. Gossot D, Seguin-Givelet A. Anatomical variations and pitfalls to know during thoracoscopic segmentectomies. J Thorac Dis 2018;10:S1134-44. [Crossref] [PubMed]
21. Brunelli A, Decaluwe H, Gonzalez M, et al. European Society of Thoracic Surgeons expert consensus recommendations on technical standards of segmentectomy for primary lung cancer. Eur J Cardiothorac Surg 2023;63:ezad224. [Crossref] [PubMed]
22. Yendamuri S, Dhillon SS, Groman A, et al. Effect of the number of lymph nodes examined on the survival of patients with stage I non-small cell lung cancer who undergo sublobar resection. J Thorac Cardiovasc Surg 2018;156:394-402. [Crossref] [PubMed]
23. Nagano M, Sato M. Impact of surgical margin after sublobar resection of lung cancer: a narrative review. J Thorac Dis 2023;15:5750-9. [Crossref] [PubMed]
24. Razi SS, Nguyen D, Villamizar N. Reply from authors: Positive nodes after segmentectomy: Take a deep breath and give adjuvant treatment. J Thorac Cardiovasc Surg 2020;160:e86-7. [Crossref] [PubMed]
25. Rocha Júnior E, Terra RM. Robotic lung resection: a narrative review of the current role on primary lung cancer treatment. J Thorac Dis 2022;14:5039-55. [Crossref] [PubMed]
26. Gao Y, Jiang J, Xiao D, et al. Robotic-assisted thoracic surgery following neoadjuvant chemoimmunotherapy in patients with stage III non-small cell lung cancer: A real-world prospective cohort study. Front Oncol 2022;12:969545. [Crossref] [PubMed]
27. Mao J, Tang Z, Mi Y, et al. Robotic and video-assisted lobectomy/segmentectomy for non-small cell lung cancer have similar perioperative outcomes: a systematic review and meta-analysis. Transl Cancer Res 2021;10:3883-93. [Crossref] [PubMed]
28. Pan H, Zou N, Tian Y, et al. Short-term outcomes of robot-assisted versus video-assisted thoracoscopic surgery for non-small cell lung cancer patients with neoadjuvant immunochemotherapy: a single-center retrospective study. Front Immunol 2023;14:1228451. [Crossref] [PubMed]
29. Thomas PA, Seguin‑Givelet A, Pages PB, et al. Real-world outcomes of lobectomy, segmentectomy and wedge resection for the treatment of stage c-IA lung carcinoma. Eur J Cardiothorac Surg 2024;66:ezae251. [Crossref] [PubMed]
30. Forde PM, Spicer J, Lu S, et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med 2022;386:1973-85. [Crossref] [PubMed]
31. Awad MM, Forde PM, Girard N, et al. Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer. J Clin Oncol 2025;43:1453-62. [Crossref] [PubMed]
32. Girard N, Besada M, Rogula B, et al. Comparative Efficacy of Neoadjuvant Nivolumab Plus Chemotherapy versus Conventional Comparator Treatments in Resectable Non-Small-Cell Lung Cancer: A Systematic Literature Review and Network Meta-Analysis. Cancers (Basel) 2024;16:2492. Erratum in: Cancers (Basel) 2025;17:674. [Crossref] [PubMed]
33. Chan JWY, Lau RWH, Ngai JCL, et al. Transbronchial microwave ablation of lung nodules with electromagnetic navigation bronchoscopy guidance-a novel technique and initial experience with 30 cases. Transl Lung Cancer Res 2021;10:1608-22. [Crossref] [PubMed]
34. Abbosh C, Frankell AM, Harrison T, et al. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA. Nature 2023;616:553-62. [Crossref] [PubMed]
35. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 2017;545:446-51. Erratum in: Nature 2018;554:264.
36. Tran HT, Heeke S, Sujit S, et al. Circulating tumor DNA and radiological tumor volume identify patients at risk for relapse with resected, early-stage non-small-cell lung cancer. Ann Oncol 2024;35:183-9. [Crossref] [PubMed]
37. Ardila D, Kiraly AP, Bharadwaj S, et al. End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography. Nat Med 2019;25:954-61. Erratum in: Nat Med 2019;25:1319.
38. Ardila D, Kiraly AP, Bharadwaj S, et al. Author Correction: End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography. Nat Med 2019;25:1319. Erratum for Nat Med 2019;25:954-61.
39. Dolezal JM, Kochanny S, Zhu A, et al. The use of artificial intelligence with uncertainty estimation to predict lung cancer relapse from histopathology. J Clin Oncol 2022;40:8549.
40. Akram F, Wolf JL, Trandafir TE, et al. Artificial intelligence-based recurrence prediction outperforms classical histopathological methods in pulmonary adenocarcinoma biopsies. Lung Cancer 2023;186:107413. [Crossref] [PubMed]
41. Kanan M, Alharbi H, Alotaibi N, et al. AI-Driven Models for Diagnosing and Predicting Outcomes in Lung Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024;16:674. [Crossref] [PubMed]