Minimally invasive vs. open chest wall resection in non-small cell lung cancer: a systematic review and meta-analysis
Original Article

Minimally invasive vs. open chest wall resection in non-small cell lung cancer: a systematic review and meta-analysis

Paula Duarte D’Ambrosio1, Rachid Eduardo Noleto da Nobrega Oliveira2, Marcelo Albuquerque Barbosa Martins3, Isabella Cabianca Moriguchi Caetano Salvador4, Luiza Gonzalez de Andrade5, Ricardo Mingarini Terra1, Paulo Manuel Pêgo-Fernandes6, José Ribas Milanez Campos1,6

1Department of Thoracic Surgery, Hospital das Clinicas de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; 2Department of Thoracic Surgery, Barretos Cancer Center, São Paulo, SP, Brazil; 3Federal University Ouro Preto, Minas Gerais, Brazil; 4University Anhembi Morumbi, São Paulo, SP, Brazil; 5University Santo Amaro, São Paulo, SP, Brazil; 6Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

Contributions: (I) Conception and design: PD D’Ambrosio, REN da Nobrega Oliveira; (II) Administrative support: RM Terra, PM Pêgo-Fernandes, JRM Campos; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: ICMC Salvador, LG de Andrade; (V) Data analysis and interpretation: MAB Martins; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Paula Duarte D’Ambrosio, MD. Department of Thoracic Surgery, Hospital das Clinicas de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Dr. Ovídio Pires de Campos, 225 - Cerqueira César, Sao Paulo, SP 05403-010, Brazil. Email: pauladuartedambrosio94@gmail.com.

Background: Minimally invasive chest wall resection (MICWR) has emerged as an alternative to open chest wall resection (OCWR) for lung cancer. This meta-analysis aims to compare perioperative outcomes between MICWR and OCWR in order to evaluate the safety and feasibility of the minimally invasive approach.

Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted until January 20, 2025, for studies comparing MICWR and OCWR in adult patients with non-small cell lung cancer (NSCLC). The effect measures included odds ratios (ORs) for binary outcomes and mean differences (MDs) for continuous outcomes. Statistical analysis was performed using random-effects models. Heterogeneity was assessed with I2 statistics.

Results: Three retrospective studies comprising 2,973 patients were included, with 26.3% undergoing MICWR and 73.7% undergoing OCWR. No significant differences were found in overall mortality [OR 1.12; 95% confidence interval (CI): 0.95 to 1.32; P=0.17; I2=0%] or 90-day mortality (OR 1.00; 95% CI: 0.74 to 1.34; P=0.98; I2=0%). MICWR significantly reduced overall complications (OR 0.36; 95% CI: 0.14 to 0.93; P=0.04; I2=0%). While primary analysis showed no significant difference in length of stay (LOS) (MD −4.92 days; 95% CI: −10.36 to 0.52; P=0.08; I2=84%), sensitivity analysis (leave-one-out) eliminated heterogeneity (I2=0%) and showed a significant LOS reduction favoring MICWR (MD −7.62 days; 95% CI: −11.34 to −3.90).

Conclusions: MICWR offers comparable oncologic outcomes to OCWR while reducing postoperative complications. It may also shorten LOS in selected patients. However, evidence is limited to retrospective studies, warranting prospective trials to confirm these findings and define optimal criteria.

Keywords: Non-small cell lung cancer (NSCLC); chest wall resection (CWR); minimally invasive surgery (MIS); video-assisted thoracoscopic surgery (VATS); robotic-assisted thoracic surgery (RATS)

Submitted Mar 24, 2025. Accepted for publication May 09, 2025. Published online Jul 28, 2025.

doi: 10.21037/tlcr-2025-358

Highlight box

Key findings

• Minimally invasive chest wall resection (MICWR) for primary lung cancer is associated with reduced postoperative complications, shorter hospital stay, and similar oncological outcomes when compared to open chest wall resection (OCWR).

What is known and what is new?

• It is known that OCWR has traditionally been the standard approach for tumors invading the chest wall, but it is associated with significant morbidity.

• This manuscript adds a systematic comparison of MICWR and OCWR, showing that minimally invasive techniques may offer equivalent oncologic safety with improved perioperative outcomes.

What is the implication, and what should change now?

• The findings support the adoption of minimally invasive approaches for selected patients with chest wall invasion, prompting thoracic surgeons to consider MICWR as a feasible and potentially superior alternative in terms of recovery without compromising cancer control. Clinical guidelines and surgical training should increasingly incorporate minimally invasive chest wall techniques.

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases (1-3). Surgical resection remains the primary curative treatment for early-stage NSCLC, and in cases where the tumor involves the chest wall, chest wall resection (CWR) is necessary to achieve complete oncologic resection (4,5). Traditionally, CWR has been performed using an open thoracotomy approach, which provides excellent exposure but is associated with significant morbidity, including postoperative pain, prolonged hospital stay, and respiratory complications (6). With advancements in surgical techniques, minimally invasive surgery (MIS), including video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS), has emerged as an alternative approach for CWR, aiming to reduce surgical trauma while maintaining oncologic effectiveness (7).

Despite the increasing adoption of MIS for lung cancer surgery, the role of minimally invasive CWR (MICWR) in NSCLC remains controversial (8). Proponents argue that MICWR can offer comparable oncologic outcomes to open surgery while reducing complications and enhancing recovery (9,10). However, concerns exist regarding its feasibility in complex CWRs, particularly in cases requiring extensive resection or reconstruction. Furthermore, the long-term oncologic equivalence between MIS and open CWR has not been definitively established, as studies have reported conflicting results regarding recurrence rates, margin status, and survival outcomes (11). Current clinical practice remains variable, with some centers favoring MIS approaches while others adhere to traditional open techniques based on surgeon preference and institutional experience (12,13).

Given this ongoing debate, we performed systematic review and meta-analysis evaluating the efficacy and safety of minimally invasive versus open CWR (OCWR) in NSCLC, incorporating the latest available data to guide surgical decision-making and optimize patient outcomes. We present this article in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-358/rc).

Methods

The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42025644781.

Search strategy and data extraction

We conducted a systematic search of PubMed, Embase, and Cochrane Library from inception through January 20, 2025. The full search strategy is detailed in the Appendix 1. Studies were initially imported into EndNote for deduplication and then into Zotero for screening. Each study was reviewed in Zotero at the title, abstract, and full-text levels based on inclusion and exclusion criteria. Two authors (R.E.N.N.O.) and (I.C.M.C.S.) independently extracted baseline characteristics and outcome data. Disagreements were resolved by consensus with a third author (P.D.D.).

Eligibility criteria

Studies meeting the following criteria were included: retrospective studies or randomized controlled trials (RCTs); comparisons between CWR performed via a minimally invasive approach and thoracotomy; enrollment of adult patients (>18 years old) undergoing CWR for primary lung cancer; and reporting at least one outcome of interest. Articles with overlapping populations or treatments were excluded. No language restrictions were applied.

Endpoints

The endpoints of interest were: overall mortality, mortality in 90 days, length of stay (LOS), and overall complication.

Risk of bias and publication bias

The risk of bias of flexible-randomized studies was assessed by Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I) (14). Each study received a low, moderate, serious, or critical risk of bias in seven domains: confounding; selection of participants; classification of interventions; deviations from intended interventions; missing data; measurement of outcomes, and selection of reported results. Two independent authors conducted the risk of bias assessment (M.A.B.M. and R.E.N.N.O.) and disagreements were resolved unanimously with the senior author (J.R.M.C.).

Quality assessment

The overall quality of the evidence was assessed following the Grading of Recommendation, Assessment, Development, and Evaluations (GRADE) guidelines (15). Non-randomized retrospective studies were categorized as having very low, low, moderate, or high-quality evidence, depending on factors such as risk of bias, result inconsistency, imprecision, publication bias, and the magnitude of treatment effects.

Statistical analysis

Continuous outcomes were analyzed using mean differences (MDs) or standardized MDs (SMDs), and binary endpoints were summarized by odds ratios (ORs), each with 95% confidence intervals. Between-study heterogeneity was evaluated using Cochran’s Q test and the I2 statistic, with P<0.10 and I2>25% indicating significant heterogeneity (16). DerSimonian and Laird random effects models were used for all endpoints (17). Leave-one-out sensitivity analysis was performed for the LOS and overall complications outcomes. The Cochrane Handbook for Systematic Reviews of Interventions was used for data handling and conversion (16). Statistical analyses were performed using R software, version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Study selection and characteristics

A comprehensive search strategy identified a total of 295 articles, as illustrated in Figure 1. After the removal of duplicates and initial screening, 267 articles were excluded due to their titles and abstracts not meeting the inclusion criteria, leaving 28 studies for full-text review. Ultimately, 3 studies were included in this meta-analysis, comprising a total of 2,973 patients, of whom 783 patients (26.3%) underwent resection of the chest wall with minimally invasive and 2,190 (73.7%) with open surgery (18-20). Among the studies included in the meta-analysis, Berry et al. exclusively reported patients with negative surgical margins (18), whereas Purnell et al. included both negative and positive margins, with the majority being negative (20). In contrast, Hennon et al. did not provide information regarding margin status (19). The characteristics of the included studies are summarized in Table 1.

Figure 1 PRISMA flow diagram of study screening and selection. PRISMA, Preferred Reporting Items for Systematic Review and Meta-Analysis.

Table 1

Baseline characteristics of included studies

Characteristics Berry 2011 Hennon 2015 Purnell 2024
Minimally invasive Open Minimally invasive Open Minimally invasive Open
Population 12 93 15 16 756 2,081
Period 2000–2010 2007–2013 2010–2020
Type of study Retrospective study Retrospective study Retrospective study
Country USA USA USA
Margins (negative) 12 (100.0) 93 (100.0) NA NA 641 (84.8) 1,646 (79.0)
Age, years 60±13.1 59.76±10.9 76† 56† 66.0±9.9 65.2±9.8
Tumor size 5.6±2.6 cm 5.4±2.5 cm NA NA <5 cm (n=353);
≥5 cm (n=403)		 <5 cm (n=728);
≥5 cm (n=1,353)
FEV1 (% predicted) 72.0±25.4 67.8±17.3 NA NA NA NA
DLCO (% predicted) 69.4±17.8 66.0±19.1 NA NA NA NA
Comorbidities
   Coronary artery disease 3 15 NA NA NA NA
   Tobacco abuse 10 52 NA NA NA NA
   Chronic obstructive pulmonary disease 5 22 NA NA NA NA
   Diabetes 1 5 NA NA NA NA
   Congestive heart failure 0 1 NA NA NA NA
   Hypertension 5 34 NA NA NA NA
Histology
   Adenocarcinoma NA NA 5 9 274 735
   Squamous cell NA NA 5 4 340 977
   NSCLC, others NA NA 5 3 142 369
Type of surgery
   Lobectomy (MI/Open) 12 (100.0) 93 (100.0) 14 (93.3) 15 (93.8) 756 (100.0) 2,081 (100.0)
   Pneumonectomy (MI/Open) 0 (0) 0 (0) 1 (6.7) 1 (6.2) 0 (0) 0 (0)
Pathologic stage (TNM)
   I 0 0 1 1 90 179
   II 12 64 10 10 414 1,235
   III 0 27 4 4 219 563
   IV 0 2 0 1 33 104
Multimodal therapy (MI/Open)
   Neoadjuvant therapy 4 (33.0) 52 (55.9) 10 (66.7) 10 (62.5) 113 (14.9) 455 (21.9)
   Adjuvant therapy NA NA NA NA 301 (39.8) 787 (37.8)
   Perioperative therapy 0 0 0 0 28 (3.7) 109 (5.2)
Surgical details
   Reconstruction with mesh 4 40 1 9 NA NA
   Number of resected ribs 3.1±0.9
(median)		 3.3±0.9 (median) 3
(range, 1–5)		 3
(range, 1–5)		 NA NA

Data are presented as number of patients, mean ± standard deviation, or n (%). †, median values reported in some studies. DLCO, diffusing capacity of lung for carbon monoxide; FEV1, forced expiratory volume in 1 second; MI, minimally invasive; NA, not available; NSCLC, non-small cell lung cancer; Open, open surgery; TNM, tumor-node-metastasis.

Pooled analysis of all studies

In the pooled analysis, there were no significant differences between the minimally invasive technique and open surgery groups for overall mortality (OR 1.12; 95% CI: 0.95 to 1.32; P=0.17; I2=0%; Figure 2A), mortality in 90 days (OR 1.00; 95% CI: 0.74 to 1.34; P=0.98; I2=0%; Figure 2B), LOS (MD −4.92 days; 95% CI: −10.36 to 0.52; P=0.08; I2=84%; Figure 3A) and overall complication (OR 0.36; 95% CI: 0.14 to 0.93; P=0.04; I2=0%; Figure 3B).

Figure 2 Forest plots of mortality outcomes in lung cancer patients undergoing minimally invasive vs. open chest wall resection. (A) Overall mortality and (B) 90-day mortality. CI, confidence interval; MH, Mantel-Haenszel.
Figure 3 Forest plots of postoperative outcomes in lung cancer patients undergoing minimally invasive vs. open chest wall resection. (A) Length of stay and (B) overall complications. CI, confidence interval; IV, inverse variance; MH, Mantel-Haenszel; SD, standard deviation.

Sensitivity analysis

We performed a leave-one-out sensitivity analysis for LOS and overall morbidity. The withdrawal of the Purnell et al. (20) in LOS outcome eliminated the heterogeneity and changed the significance (MD −7.62 days; 95% CI: −11.34 to −3.90; I2=0%; Figure S1), favoring the minimally invasive technique.

Risk of bias and publications bias

As illustrated in Figure 4, we applied the ROBINS-I tool to assess risk of bias, and all three studies showed a moderate overall risk of bias, primarily due to selection bias (D2) and missing data (D5). Since the studies are observational and retrospective, confounding was a concern, but it was rated as low risk (D1) across all studies. Other domains, including classification of interventions (D3), deviations from intended interventions (D4), measurement of outcomes (D6), and selection of reported results (D7), had a low risk of bias. While some methodological limitations exist, the results remain valuable but should be interpreted with caution.

Figure 4 Critical appraisal of studies according to ROBINS-I. ROBINS-I, Risk of Bias In Non-randomized Studies - of Interventions.

Quality assessment

According to the GRADE assessment, one outcome evaluated in this study was classified as high-quality evidence: According to the GRADE assessment, the outcomes evaluated in this study were overall mortality, 90-day mortality, length of hospital stay, and overall complications. Length of hospital stay was classified as very low-quality evidence. Overall mortality, 90-day mortality, and overall complications were classified as moderate-quality evidence. The main factors responsible for reducing the quality of evidence were high heterogeneity and the observational retrospective design of the included studies. A detailed quality assessment is available in the Figure S2, and GRADE assessment is detailed in the Figure S3.

Discussion

This systematic review and meta-analysis evaluated three studies involving 2,973 patients who underwent minimally invasive or OCWR for non-small cell lung cancer (18-20). Our findings indicate no significant difference in overall mortality or 90-day mortality between the two approaches. However, minimally invasive techniques were associated with a significant reduction in overall complications, suggesting a potential clinical advantage. Furthermore, sensitivity analysis demonstrated that excluding one study (Purnell et al.) eliminated heterogeneity and altered the significance of length of hospital stay (20), favoring the minimally invasive approach.

The role of minimally invasive thoracic surgery (MITS) in oncologic lung resection has expanded over the past decade, but its application in cases requiring CWR remains controversial (11,21). Traditional open thoracotomy has been considered the gold standard, mainly due to its superior exposure, which facilitates large resections and complex reconstructions (9,22,23). However, recent studies suggests that VATS and RATS may offer similar oncologic outcomes while enhancing postoperative recovery (24-26). Our findings align with this trend, indicating that minimally invasive approaches may reduce overall complications without compromising survival outcomes.

One of the key advantages associated with minimally invasive techniques is a shorter hospital stay, particularly after pulmonary resection (27,28). While our primary analysis showed a non-significant reduction in LOS, the sensitivity analysis (leave-one-out) demonstrated a significant benefit in favor of the minimally invasive approach when the study by Purnell et al. was excluded (20). This suggests that institutional variability and differences in postoperative protocols may influence this outcome. Previous studies have shown that VATS and RATS facilitate earlier mobilization, reduce ventilatory support, and improve postoperative pain control, leading to faster discharge (29-31). However, variations in discharge criteria, rehabilitation protocols, and pain management among different institutions could explain the heterogeneity observed in LOS.

Beyond hospital stay, our meta-analysis found that MIS significantly reduced overall complications. The lower surgical trauma, reduced blood loss, and preservation of respiratory mechanics associated with MITS may explain the lower pulmonary and infectious complication rates (32-35). These findings reinforce previous reports indicating that minimally invasive techniques improve postoperative outcomes in thoracic surgery. Despite the potential benefits of MITS, patient selection remains crucial. Tumors with extensive chest wall invasion often require complex en-bloc resections and reconstruction, which may limit the feasibility of minimally invasive approaches (36-38). Additionally, the surgeon’s expertise plays a critical role in determining outcomes, as MITS for CWR requires a longer learning curve (39-41).

This meta-analysis has notable limitations. First, the exclusive inclusion of retrospective studies may have introduced selection bias. To mitigate this, we conducted sensitivity analyses. Additionally, the small number of studies (n=3) limits generalizability and precludes a subgroup analysis. Another limitation was the lack of complete data on surgical margins, a crucial factor in assessing oncologic effectiveness. Lastly, the high heterogeneity in the length of hospital stay analysis suggests that institutional factors and differences in postoperative recovery may have influenced the results.

Given these limitations, prospective, multicenter RCTs are urgently needed to confirm the efficacy and safety of MICWR. Future research should also explore long-term oncologic outcomes, including local recurrence and disease-free survival, to determine whether MITS can match the oncologic effectiveness of open surgery in the long run.

Conclusions

MICWR in non-small cell lung cancer demonstrated comparable oncologic outcomes to open thoracotomy while significantly reducing postoperative complications. Sensitivity analysis further suggested a potential benefit in shortening hospital stay, although institutional variability may influence this outcome. Despite these advantages, the current evidence is limited to retrospective studies, highlighting the need for high-quality prospective trials. Future research should focus on long-term oncologic outcomes, patient selection criteria, and the impact of surgeon expertise to better define the role of minimally invasive techniques in CWR.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-358/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-358/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-358/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.

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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Cite this article as: D’Ambrosio PD, da Nobrega Oliveira REN, Martins MAB, Salvador ICMC, de Andrade LG, Terra RM, Pêgo-Fernandes PM, Campos JRM. Minimally invasive vs. open chest wall resection in non-small cell lung cancer: a systematic review and meta-analysis. Transl Lung Cancer Res 2025;14(7):2626-2635. doi: 10.21037/tlcr-2025-358

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