The safety and feasibility of non-intubated versus intubated video-assisted thoracic surgery in NSCLC patients after neoadjuvant therapy: a propensity score matching study

Introduction

Lung cancer remains the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases (1). Surgical resection is the cornerstone of treatment for early-stage NSCLC; however, patients presenting with locally advanced disease or high-risk factors often require neoadjuvant therapy to improve resectability and survival outcomes (2). Compared to open thoracotomy, video-assisted thoracoscopic surgery (VATS) has become the standard approach due to its minimally invasive nature, faster recovery, and superior long-term efficacy (3-5).

Advancements in thoracoscopic techniques and enhanced recovery after surgery (ERAS) protocols have driven the adoption of non-intubated video-assisted thoracoscopic surgery (NI-VATS). NI-VATS utilizes laryngeal mask airway (LMA) support for spontaneous ventilation, avoiding the airway trauma associated with double-lumen endotracheal intubation used in intubated VATS (I-VATS). This approach reduces common postoperative complications such as hoarseness, cough, and sore throat (6-8). Regarding ventilation strategies, I-VATS relies on single-lung ventilation [tidal volume: 6 mL/kg, positive end-expiratory pressure (PEEP): 5–10 cmH₂O] (9), whereas NI-VATS employs low-tidal-volume spontaneous breathing (3–4 mL/kg), potentially reducing ventilator-induced lung injury and systemic inflammation (10-13). Furthermore, NI-VATS minimizes neuromuscular blockade and opioid use, preserves mucociliary clearance, and lowers the risk of atelectasis and infection, thereby accelerating recovery (14,15).

Although NI-VATS has demonstrated advantages in specific populations, its safety in patients undergoing neoadjuvant therapy remains insufficiently explored. Following neoadjuvant treatment, patients may experience treatment-induced tissue fibrosis, adhesions, and vascular fragility (16,17). Concurrently, concerns persist among some surgeons and researchers regarding the technique’s safety due to the relatively unstable surgical field and increased mediastinal motion associated with NI-VATS, which heighten surgical complexity. Although NI-VATS has demonstrated tumor efficacy comparable to I-VATS (18) and improved postoperative outcomes (7,19-21), evidence supporting its use in neoadjuvant therapy patients remains limited(some studies excluded NSCLC patient after neoadjuvant therapy). Therefore, we sought to investigate the safety and feasibility of NI-VATS in NSCLC patients following neoadjuvant therapy, aiming to provide evidence for optimizing surgical strategies in this patient population. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2742/rc).

Methods

Research object

This study retrospectively collected clinical data from patients with NSCLC who underwent surgical treatment at the Department of Thoracic Surgery, Affiliated Hospital of Hebei University between June 2022 and December 2024. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Affiliated Hospital of Hebei University (Ethics Approval Number: HDFYLL-IIL-2025-027). Due to its retrospective design and use of anonymized data, the requirement for individual informed consent was waived.

Inclusion criteria: (I) pathologically diagnosed with NSCLC; (II) received neoadjuvant therapy prior to surgery; (III) pre-treatment staging of IIB to III, with post-treatment assessment confirming resectability; (IV) underwent thoracoscopic lobectomy and lymph node dissection.

Exclusion criteria: (I) history of lung surgery; (II) severe cardiovascular or cerebrovascular disease; (III) patients undergoing open thoracotomy; (IV) incomplete clinical data; (V) concurrent other cancers; (VI) tumor recurrence/multiple primary tumors (Figure 1).

Figure 1 Flow chart of study population. I-VATS, intubated video-assisted thoracic surgery; NI-VATS, non-intubated video-assisted thoracic surgery; PSM, propensity score matching.

Anesthesia surgery plan and patient management

All patients abstained from smoking for at least two weeks prior to surgery. Upon admission, preoperative preparations included respiratory nebulization and pulmonary function exercises. Anxiety was alleviated before surgery, and standardized preoperative assessments were conducted.

All patients signed informed consent forms for either NI-VATS or I-VATS, which included explanations of the reasons for surgery, surgical approach, risks, and benefits. The type of surgery was jointly determined preoperatively by the experienced operating surgeon, anesthesiologist, and patient. The NI-VATS group served as the study group, while the I-VATS group served as the control group.

The inclusion criteria for NI-VATS are as follows: American Society of Anesthesiologists (ASA) Classification 1 or 2, absence of severe cardiovascular or cerebrovascular disease, and body mass index (BMI) below 28 kg/m² (22).

Upon entering the operating room, routine antibiotics were administered for infection prevention, and vital signs were monitored. For NI-VATS patients, the Bispectral Index (BIS) was additionally monitored to maintain target sedation levels between 40 and 60.

I-VATS group: upon readiness, intravenous induction with midazolam, sufentanil, etomidate, cisatracurium, and propofol was administered. Following successful induction, double-lumen endotracheal intubation was performed. Intraoperative maintenance involved a combination of inhaled remifentanil, propofol, and desflurane. Deflutide inhalation was discontinued 10–15 minutes before surgery completion. An intercostal nerve block was administered prior to skin closure, and infusions of remifentanil and propofol were ceased after skin closure was completed.

NI-VATS group: the anesthesiologist used ultrasound to locate the thoracic paravertebral space corresponding to the surgical incision, and injected 0.375% bupivacaine 20 mL to complete the thoracic paravertebral block (TPVB), and injected 2% lidocaine 5 mL on the C6 plane to complete the operative side of the vagal nerve block. Following successful nerve blockade, anesthesia was induced with alfentanil, propofol, etomidate and midazolam. Following successful induction, a laryngeal mask was inserted. Intraoperative anesthesia maintenance involved combined inhalation of alfentanil, dexmedetomidine, propofol, and desflurane. Desflurane inhalation was discontinued 10–15 minutes before the end of surgery. An intercostal nerve block was administered prior to skin closure. Arterial blood was drawn for blood gas analysis during the procedure. Necessary interventions were performed based on the blood gas results. Infusion of anesthetic maintenance agents was discontinued after completion of skin closure.

Indications for endotracheal intubation: persistent cough unresponsive to vagal maneuvers, persistent hypoxemia (arterial PaO₂ <60 mmHg or SpO₂ <90%), and/or uncorrectable hypercapnia (arterial PaCO₂ >75 mmHg or pH <7.15), intolerance to mediastinal flutter, severe bleeding, or inadequate surgical exposure.

Postoperative management: all patients follow standardized ERAS protocols. Routinely assess patient consciousness and pain levels within 24 hours; resume oral intake once bowel sounds return to 4 per minute with no nausea or vomiting. On postoperative day 1, repeat laboratory tests including CBC, liver function, renal function, and chest imaging. Routinely record drainage volume; remove drainage tubes when no air leakage is present and drainage volume is <200 mL/24 h. Following drainage tube removal, patients may be discharged if vital signs are stable, white blood cell count is below 10×10⁹, and chest X-ray shows no abnormalities. Patients return to the hospital one month postoperatively for postoperative supportive care and short-term prognosis assessment.

Data collection

Baseline data: basic information [age, gender, smoking status (yes/no), BMI], tumor characteristics [pathological type (squamous/adenocarcinoma), pre-treatment clinical stage (II/III), lesion location (lobe)], neoadjuvant regimen (immunotherapy-chemotherapy, targeted therapy-chemotherapy, chemotherapy, targeted therapy), preoperative laboratory values [white blood cell count (WBC, ×10⁹/L), albumin (g/L)], pulmonary function [forced expiratory volume in 1 second (FEV1, L), diffusion capacity for carbon monoxide (DLCO, predicted %)].

Intraoperative indicators: anesthesia method (I-VATS or NI-VATS), operative time (min), intraoperative blood loss (mL), number of lymph node dissection stations and total lymph nodes removed, R0 resection rate (%), auxiliary airway removal time (min, defined as the time from completion of skin closure to removal of LMA or ETT).

Postoperative indicators: postoperative 24-hour white blood cell count (×10⁹/L), 24-hour albumin (g/L), postoperative fasting duration (h), postoperative day 1 drainage volume (mL), total drainage volume (mL), postoperative hospital stay (d), Total hospitalization cost (¥), postoperative 8- and 24-hour pain scores [Visual Analogue Scale (VAS)], postoperative adverse events: pleural effusion requiring intervention, persistent pneumothorax, respiratory tract infection, atelectasis, gastrointestinal discomfort, postoperative delirium, hoarseness, sore throat, irritating cough.

Statistical analysis

Statistical analysis was performed using SPSS 27.0. Based on collected baseline information, patients were grouped according to anesthesia technique (NI-VATS vs. I-VATS). Propensity scores were calculated using logistic regression, incorporating 12 covariates (e.g., gender, age, smoking history, BMI, neoadjuvant approach, tumor histology, pre-treatment stage, and lesion location). A 1:1 matching was performed, with a calibration threshold of 0.02.

Continuous variables are expressed as mean ± standard deviation. Independent samples t-tests were used for intergroup comparisons. Non-normally distributed continuous variables are presented as median (25–75%), with comparisons performed using the Mann-Whitney U test. Categorical variables are reported as frequencies (%). Intergroup comparisons were conducted using chi-square tests or Fisher’s exact probability test. P<0.05 was considered statistically significant.

Results

A total of 186 eligible cases were screened based on inclusion and exclusion criteria, comprising 37 cases in the NI-VATS group and 149 cases in the I-VATS group. One patient in the NI-VATS group underwent conversion to open surgery due to intraoperative bleeding. Four patients in the I-VATS group underwent conversion to open surgery due to intraoperative bleeding, calcified lymph nodes, or extensive pleural adhesions. These five patients were additionally excluded. No surgery-related deaths occurred. No patients in the NI-VATS group required endotracheal intubation during the procedure. The baseline data for the remaining 181 patients are shown in Table 1. After propensity score matching, 31 well-matched pairs were obtained for analysis (Figure 1).

Baseline data

After PSM, baseline characteristics including patient demographics and tumor features were balanced between the two groups (P>0.05, Table 2).

Intraoperative indicators

There were no statistically significant differences between the two groups in terms of operative time, blood loss, number of lymph node groups dissected, number of lymph nodes removed, or R0 resection rate (P>0.05). However, the NI-VATS group demonstrated a 36.7% reduction in anesthesia auxiliary airway removal time compared to the I-VATS group (12.32±10.46 vs. 19.45±6.81 min, P<0.003), with a statistically significant difference. The post-removal observation times were similar (26.61±10.42 vs. 24.10±7.58 min, P=0.25) (Table 3 and Figure 2).

Figure 2 Comparison between I-VATS and NI-VATS. I-VATS, intubated video-assisted thoracic surgery; NI-VATS, non-intubated video-assisted thoracic surgery; WBC, white blood cell.

Postoperative outcomes

There were no statistically significant differences between groups in 24-hour pain scores (24-VAS), 24-hour albumin levels, albumin change (ΔAlbumin), drainage volume on postoperative day 1, or total drainage volume (P>0.05 for all, Table 3).

The NI-VATS group demonstrated significantly lower pain scores at 8 hours postoperatively (8-VAS, 3.81±1.68 vs. 4.84±1.10, P=0.006). The NI-VATS group also exhibited significantly shorter postoperative fasting duration (6.39±6.61 vs. 10.48±6.53 h, P=0.02). The NI-VATS group exhibited reduced postoperative inflammatory response, with lower 24-hour WBC counts (11.10±2.20 vs. 12.79±3.50 ×10³/L, P=0.03) and a smaller increase in WBC (ΔWBC: 5.24±2.12 vs. 7.00±3.23 ×10/L, P=0.02), with statistically significant differences (Table 3).

Additionally, the NI-VATS group exhibited significantly lower rates of certain postoperative adverse events: postoperative delirium (6.5% vs. 25.8%, P=0.04), irritating cough (9.7% vs. 41.9%, P=0.01), sore throat/hoarseness (16.1% vs. 51.6%, P=0.003), and respiratory tract infection (0% vs. 12.9%, P=0.04). There were no significant differences in the incidence of pleural effusion requiring intervention, persistent pneumothorax, atelectasis, or gastrointestinal discomfort (P>0.05, Table 4).

Finally, the postoperative hospital stay was significantly shorter in the NI-VATS group (6.58±2.43 vs. 9.22±4.87 days, P=0.009), and the total hospitalization cost was significantly lower in the NI-VATS group (47,324.90±6,976.54 vs. 51,477.78±4,939.09 CNY, P=0.009), with statistically significant differences (Table 3).

All 62 patients received further treatment at our hospital within one month postoperatively, with no complications requiring hospitalization during this period.

Additionally, we conducted the Mini-Mental State Examination (MMSE) preoperatively, at 3 days postoperatively, and at 1 month postoperatively for 64 neoadjuvant patients who underwent lobectomy at our hospital between March 2024 and October 2024. After excluding 31 patients with incomplete data, lost to follow-up, or refusal to undergo testing, as well as 4 patients with a preoperative MMSE score <24, A total of 29 patient records were collected (13 in the NI-VATS group and 16 in the I-VATS group). A preoperative-to-postoperative score difference greater than 3 points was used to define cognitive decline. Results showed that the incidence of cognitive decline at 3 days postoperatively was lower in the NI-VATS group than in the I-VATS group, but the difference was not statistically significant. There was no difference in the incidence of postoperative functional cognitive decline at 1 month postoperatively (Table 5).

Discussion

This retrospective cohort study of PSM demonstrates that NI-VATS is a safe and feasible alternative to conventional I-VATS for NSCLC patients undergoing resection after neoadjuvant therapy. Crucially, NI-VATS offers significant advantages in accelerating postoperative recovery and reducing complications, aligning well with ERAS principles.

In terms of intraoperative indicators (operative time, blood loss, lymph node dissection extent, R0 resection rate), the equivalence between the NI-VATS and I-VATS groups, along with comparable conversion rates to open surgery (2.70% vs. 2.68%, P=0.585), provides strong evidence for the feasibility and oncological safety of NI-VATS in specific patient populations following neoadjuvant therapy. Although treatment-related tissue alterations (e.g., fibrosis, vascular fragility) (16,17) may increase surgical difficulty, they did not compromise patient safety during actual procedures. Furthermore, no significant differences were observed in postoperative drainage volume or albumin levels, further confirming comparable surgical trauma and physiological stress levels between groups.

In this study, we clearly observed that compared with the I-VATS group, in the NI-VATS group the anesthesia auxiliary airway removal time was 36.7% shorter (95% CI: 15.33–57.99%, P=0.003) and the postoperative fasting time was 39.0% shorter (95% CI: 12.03–66.03%, P=0.02). We attribute this to the anesthesia strategy employed for spontaneous-breathing surgery. Related literature indicates that this technique reduces intraoperative opioid use by over 50%, diminishing respiratory center suppression and thereby shortening the time to removal auxiliary airway after anesthesia (23). Furthermore, reduced opioid use decreases postoperative nausea and vomiting incidence, facilitating earlier dietary resumption (24). Furthermore, NI-VATS preserves spontaneous breathing, thereby reducing the risk of diaphragmatic paralysis, promoting early postoperative respiratory function recovery, and shortening the required fasting period to prevent aspiration (25).

Regarding postoperative pain, we found no significant difference in 24-hour VAS scores between the two groups. However, the 8-hour VAS scores were lower in the NI-VATS group, which we attribute to the individualized analgesic regimen involving preoperative paravertebral thoracic nerve block in this group. Postoperative pain can limit patients’ ability to cough effectively and clear secretions, leading to inadequate removal of sputum and airway secretions. This increases the risk of atelectasis and pulmonary infection (14). Therefore, the difference in regional anesthesia techniques between groups constitutes an important confounding factor in this retrospective study, which may contribute to the between‑group differences in early postoperative pain and related pulmonary outcomes. Preoperative paravertebral thoracic nerve block and intercostal nerve block show advantages in postoperative pain relief, which is conducive to promoting patient recovery and enhancing patient experience. This technique is equally applicable for pain management in I-VATS patients and is recommended for wider adoption.

In terms of inflammatory response, patients in the NI-VATS group exhibited lower inflammatory markers compared to those in the I-VATS group. Intraoperatively, we clearly observed differences in tidal volume between the two groups. Tidal volume in the NI-VATS group generally ranged from 150–250 mL, while that in the I-VATS group typically ranged from 350–500 mL. Tidal volume during spontaneous ventilation with the laryngeal mask was approximately 50% lower than that during mechanical ventilation, while still meeting physiological requirements. Multiple studies indicate that mechanical positive pressure ventilation induces barotrauma and biotrauma, activating the release of inflammatory mediators (26-28). Simultaneously, intubation itself induces airway trauma, triggering local and systemic inflammatory cascades (29). NI-VATS avoids both the irritation of intubation and the mechanical distension of alveoli caused by positive-pressure ventilation. Mineo et al. noted that non-intubated surgery significantly reduces systemic inflammatory responses, better preserves immune function, and consequently lowers the risk of postoperative infection (30). However, it should be noted that WBC, as a non-specific inflammatory marker, may be affected by various perioperative factors such as surgical stress, steroid administration, and prophylactic antibiotics. These confounding factors were not fully controlled in the present study; therefore, the preliminary results may be biased. In the future, we suggest introducing ESR, CRP, IL-6, PCT and other indicators for further investigation.Regarding postoperative adverse events, we observed no significant differences between the two groups in terms of postoperative pneumothorax, pleural effusion, or atelectasis. However, the incidence of postoperative delirium, irritative cough, sore throat, hoarseness, and postoperative respiratory tract infection was significantly lower in the NI-VATS group compared to the VATS group. Related studies indicate that opioid use, pain, and inflammatory responses may increase the incidence of postoperative delirium (31). Following single-lung ventilation, cerebral oxygen saturation decreases by 20% in half of patients compared to preoperative levels. During NI-VATS procedures, permitting a state of hypercapnia dilates cerebral blood vessels, regulates cerebral blood flow, and enhances intraoperative cerebral oxygenation (32), further reducing postoperative delirium incidence. Concurrently, LMA use provides comprehensive airway protection, preventing mucosal and vocal cord injury while reducing postoperative cough, sore throat, and hoarseness. Studies indicate (33,34) that tracheal intubation causes postoperative sore throat in 40–60% of cases, whereas LMA significantly lowers this incidence. Regarding respiratory tract infections, we believe intubation procedures may compromise airway defense mechanisms, increasing the risk of pathogen colonization and potential infection (35). Additionally, patients in the NI-VATS group can resume oral intake and ambulation earlier postoperatively, enabling early active coughing to clear airway secretions. This reduces the likelihood of respiratory infections, thereby effectively minimizing postoperative adverse events.

The synergistic effects of the aforementioned advantages further revealed a significant 28.6% reduction (95% CI: 11.76–45.50%, P=0.009) in postoperative hospital stay duration among patients in the NI-VATS group. This efficiency gain, coupled with decreased usage of related medications (anesthetics, opioids, infection antibiotics) and potential cost savings associated with shorter hospital stays, resulted in an average savings of 4,152.88¥ per patient (95% CI: 1,074.42–7,231.04, P=0.009). This underscores the health economic value of NI-VATS within the ERAS framework, improving patient outcomes while potentially optimizing resource utilization.

At the same time, we observed that the incidence of postoperative functional cognitive decline on day 3 was lower in the NI-VATS group than in the I-VATS group, which may be closely related to postoperative delirium status. However, no statistically significant difference was found between the two groups, likely due to the small sample size and limited statistical power. Of course, this part of the study is exploratory, and a large number of literatures and related experiments are still needed to further explore it. Research evidence indicates that NI-VATS can reduce the incidence of postoperative cognitive impairment, improve patient treatment compliance, and potentially exert positive effects on long-term survival benefits (12,36,37). Although our study focused on short-term outcomes, these potential long-term benefits warrant investigation in future research.

There are certain limitations in this study. First, the single-center retrospective design limits its generalizability. Second, small sample sizes (31 per group after PSM) may reduce statistical power and the authenticity of related data (e.g., respiratory infection rate of 0% in NI-VATS, comparison of postoperative functional cognition incidence on day 3). Third, owing to the inherent nature of retrospective research, selection bias related to surgeon preference, airway anatomy, tumor complexity, pleural adhesion, and intraoperative technical difficulty could not be fully eliminated by PSM, which may affect the comparability between groups. Fourth, although several outcomes reached statistical significance, the absolute differences (e.g., –7 minutes in auxiliary airway removal time, –4 hours in time to first oral intake, and –1.7×10⁹/L in WBC) were relatively modest. In the absence of predefined minimal clinically important differences (MCID) for these perioperative parameters, the clinical meaningfulness of these findings remains to be further validated. Thus, statistical significance does not necessarily translate into clinically relevant benefit., Finally, we lack long-term prognostic outcomes for patients. This study is an exploratory comparison. Our findings provide preliminary evidence to support the feasibility and potential benefits of NI-VATS and the choice of clinical operation requires multi-disciplinary joint decision-making and combined with the operator’s experience. Future studies should include multicenter randomized controlled trials (RCTs) and molecular biomarkers such as circulating tumor DNA (ctDNA) to evaluate NI-VATS’ impact on the tumor microenvironment and long-term prognosis, thereby further validating its clinical value.

In summary, the findings of this study provide promising initial evidence that NI-VATS is a safe, feasible, and effective surgical approach for NSCLC patients following neoadjuvant therapy. By minimizing airway manipulation, mechanical ventilation, and pharmacological burden, NI-VATS has demonstrated its advantages in enhances postoperative recovery, reduces postoperative adverse events, and reduced hospitalization costs—delivering substantial health economic value and aligning closely with ERAS objectives. It provides promising initial evidence supporting the application of NI-VATS in the neoadjuvant population as a crucial component of ERAS multimodal strategies. Further validation through larger prospective studies, including RCTs, is encouraged.

Conclusions

NI-VATS can be safely used in NSCLC patients following neoadjuvant therapy.

Crucially, NI-VATS offers significant advantages in accelerating postoperative recovery: it shortens auxiliary airway removal and fasting times, reduces inflammatory responses, lowers the incidence of postoperative adverse events (postoperative delirium, irritative cough, sore throat/hoarseness, respiratory tract infections), decreases hospital stays, and reduces hospitalization costs. These benefits align closely with the core principles of ERAS. For eligible patients, NI-VATS may serve as the preferred surgical approach. However, further evaluation and validation of NI-VATS’ clinical value warrants multicenter, large-scale, prospective RCTs.

Acknowledgments

During the preparation of this work the authors used AI in order to polish the language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2742/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2742/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2742/prf

Funding: This work was supported by Medical Science Foundation of Hebei University (2021A12).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2742/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 study was approved by the hospital’s ethics committee (Ethics Approval Number: HDFYLL-IIL-2025-027). Due to its retrospective design and use of anonymized data, the requirement for individual informed consent was waived.

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/.

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