Current advances in extended resections for non-small cell lung cancer—a narrative review

Introduction

Patients with locally advanced non-small cell lung cancer (NSCLC) represent a highly heterogenous group with different combinations of tumour size, invasion of adjacent structures, satellite lesions and nodal disease (1). In the ninth edition of the TNM classification, the T3 category includes tumours >5 cm to ≤7 cm, invasion of the parietal pleura or chest wall including superior sulcus tumours, infiltration of the pericardium, phrenic nerve or azygos vein, invasion of the thoracic nerve roots or stellate ganglion or a separate tumour nodule in the same lobe additional to the primary tumour (satellite). T4 disease includes tumours >7 cm (size), infiltration of the mediastinum, thymus, trachea, carina, recurrent laryngeal nerve, vagal nerve, oesophagus, diaphragm, heart, great vessels, vertebral body and lamina, spinal canal, cervical nerve roots or brachial plexus as well as separate nodules in a different ipsilateral lobe. Furthermore, the nodal status is subdivided into N2a single station and N2b involving multiple stations (1).

In clinical practice, this heterogeneity results in a variety of multimodal treatment pathways. While inoperable tumours are routinely managed with chemoradiotherapy followed by immunotherapy, surgery after induction therapy is the preferred treatment option in operable patients. In a small subgroup, this involves highly complex operative techniques. Complete microscopic resection remains one of the strongest prognostic determinants, yet there is no clear and universally accepted definition of resectability for tumours invading adjacent structures and judgement varies between multidisciplinary teams (MDTs), centres and countries (2-4) and is dependent on appropriate infrastructure, equipment and effective interdisciplinary cooperation (5).

This narrative review aims to synthesize current evidence on extended pulmonary resection and provide a decision-oriented framework in the current era of perioperative immunotherapy. We present this article in accordance with the Narrative Review reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0262/rc).

Methods

A narrative literature review was performed using PubMed, Embase, Scopus and Google Scholar covering English language publications from January 2000 to January 2026. Priority was given to international guidelines, expert consensus statements, randomized or prospective studies, systematic reviews or meta-analyses and recent multi-institutional or high-volume series. Since the available evidence is dominated by retrospective series with substantial heterogeneity in staging, induction regimens, operative techniques and reporting standards, we synthesized the literature narratively rather than performing a formal meta-analysis (Table S1).

Conceptual framework and common determinants of resectability

The European Organisation for Research and Treatment of Cancer (EORTC) recently published a consensus definition of technical resectability of stage III NSCLC patients to standardize inclusion into clinical trials (6). Patients with invasive N2 and N3 disease, as well as stage IIIC, are considered unresectable as well as tumours infiltrating the heart, trachea, oesophagus and spinal cord. This definition, however, is not intended to provide guidance for daily clinical decision making.

Extended resections must not be equated with T category alone. Across T3 and T4 disease, several aspects are crucially important. First, is an R0 resection technically possible? Second, is the patient functionally able to tolerate the anticipated resection and reconstruction? Third, has induction therapy demonstrated favourable tumour biology? Fourth, does the treating centre have the necessary expertise that the case may require with regard to equipment, caseload and interdisciplinary surgical and anaesthesiological cooperation? Table 1 summarizes these common determinants.

Nodal status remains pivotal. Patients with N0–1 disease derive the clearest benefit from surgery as well as single-station, non-bulky N2 disease. Invasive or multistation N2 disease (N2b) and N3 disease usually favour definitive non-surgical therapy outside a trial or a highly selected conversion/salvage setting (6-12). With the PACIFIC regimen consisting of definitive chemoradiotherapy followed by immunotherapy, a good alternative treatment strategy for inoperable patients is available (13).

Decision making in borderline resectable cases is a particular challenge. The prospective randomized phase 2 MDT Bridge trial (NCT05925530) addressed this topic in EGFR/ALK wt therapy naïve stage IIB to IIIB patients. An interim analysis showed an encouraging resection rate of 85.7% (14), however long-term survival data are not yet available.

T3 chest wall

Chest wall invasion (CWI) occurs in 5–8% of diagnosed NSCLC cases (15) and remains one of the most frequent indications for extended resections. Historically, both upfront surgery and induction chemoradiotherapy followed by surgery have been used for T3/4 N0–1 disease, which is still echoed in the current 3.2026 National Comprehensive Cancer Network (NCCN) guidelines. However, recently perioperative chemo-immunotherapy has become a standard option for resectable stage II-III NSCLC and is also relevant for tumours with chest wall infiltration (8,10,12,16-21).

Preoperative planning must define whether the tumour invades only parietal pleura or extends into intercostal muscle, ribs or the thoracic inlet. Standard work-up includes contrast-enhanced chest computed tomography (CT), positron emission tomography (PET)-CT; dedicated chest wall magnetic resonance imaging (MRI) can be helpful when CT cannot reliably distinguish pleural contact from true soft-tissue or osseous invasion, and newer CT signs such as chest wall vessel involvement may improve specificity (22-26).

The operative principle is en bloc pulmonary and chest wall resection with negative margins. Reconstruction is generally reserved for larger anterior or anterolateral defects, situations in which instability or paradoxical motion is expected, or cases in which scapular entrapment and soft-tissue deficiency would be problematic. By contrast, many posterior or apical defects are naturally covered by the scapula and paraspinal musculature and do not require rigid reconstruction (21,22,27,28).

Reported 5-year overall survival (OS) after chest wall resection ranges from roughly 24% to 52%, and selected series using induction treatment have reported survival above 50% (29-36). Across studies, nodal status, completeness of resection, tumour size and depth of invasion are the dominant prognostic variables, and pathologic rib invasion appears to be particularly adverse (37-40).

Minimally invasive strategies are increasingly used for selected chest wall tumours. Hybrid video-assisted thoracoscopic surgery (VATS) techniques and robotic-assisted thoracic surgery (RATS) can reduce rib spreading, pain and length of stay while preserving oncologic principles, although conversion is more likely with bulkier lesions or when extensive reconstruction is required (27,41-51).

T3/4 superior sulcus (Pancoast) tumours

Superior sulcus (or Pancoast) tumours are a distinct subset of NSCLC and account for <3–5% of all lung cancers (52). They are challenging to treat due to their location in the apex of the chest wall and close proximity and potential infiltration of surrounding structures such as the first rib, subclavian vessels, brachial plexus and the vertebral column. The standard treatment strategy is neoadjuvant chemo-radiotherapy followed by radical surgery so far (53-55). Posterior tumours are often addressed through posterior cervicothoracic/Paulson-type exposure, whereas anterior tumours or lesions requiring subclavian control may demand transclavicular, transmanubrial or hemi-clamshell access. When vertebral body resection is anticipated, the case should be planned jointly with spine surgeons from the outset (56-58).

The induction of neoadjuvant chemo-immunotherapy has not been established in patients with resectable Pancoast tumours and needs further validation. A small case series of six patients with resectable Pancoast tumours, who underwent surgery after neoadjuvant chemo-immunotherapy, showed an excellent pathological response rate of 100% with good short-term results and no evidence of disease progression within 6 months of follow-up (52). There are currently two studies registered in ClinicalTrials.gov. The DUMAS study investigates neoadjuvant immunotherapy for Pancoast tumours and it started in 2023 and is estimated to be completed in 2028. It consists of 3 cycles of neoadjuvant nivolumab combined with paclitaxel and carboplatin, followed by surgery and 6 months of adjuvant treatment with nivolumab if applicable and depending on pathology results. The SUPER trial, which has started in 2024 and is estimated to be completed in 04/2026, is a prospective phase II trial for patients with stage II–III sulcus, Pancoast or chest wall NSCLC treated with non-ablative oligofractionated radiation and two cycles of durvalumab prior to surgery.

Tsitsias et al. assessed the difference between anteriorly located versus posteriorly located superior sulcus tumours. Anterior tumours interestingly were identified to have a significantly higher risk of systemic recurrence and to be an independent risk factor for worse survival. However, they had lower rates of local recurrence compared with posterior tumours and an increased survival benefit from complete pathological response (53). Invasion of the subclavian artery has been shown to be a risk factor for worse survival in another study (59).

An expert opinion by Caso et al. regarding T4 Pancoast tumours recommends surgical resection after neoadjuvant therapy. As the achievement of R0 resection in this patient population remains technically challenging, it is advised to treat these individuals in high-volume centres only and to use three-dimensional imaging to plan the reconstructions. Their suggested surgical access is usually two or three incisions depending on the individual patient and to preferentially reconstruct the defect with semirigid, biologic materials and a bulky free flap to achieve good stability without impingement of the thoracic inlet neurovascular bundle if necessary (58). Despite the widespread use of minimally invasive surgery and their now well-established benefits of enhanced recovery and reduced morbidity, its use for Pancoast tumours has been limited. Nevertheless, there are hybrid and robotic approaches reported with satisfactory results, which may also represent a promising development in this special field (51,60-63). Table 2 outlines a structure-based suggestion for surgical planning in Pancoast tumours.

T4 disease by invaded structure

T4 NSCLC is the most heterogenous and most controversial subset of extended resection (1,11,59,64-70). Thus, 5-year OS spreads from 31% to 65.4% (11,54,59,66-69,71) reflecting differences in nodal disease, induction strategy, and complete resection rates (59,65-68,70).

Recent surveys and expert consensus statements underscore this uncertainty. T4 disease, defined only by tumour size or a satellite nodule in a separate ipsilateral lobe, is generally considered resectable. By contrast, invasion of the heart, oesophagus, spinal cord or unreconstructable trachea is usually considered unresectable, whereas superior vena cava (SVC), carinal, diaphragmatic, vertebral body and some great-vessel lesions are regarded as potentially resectable in carefully selected patients treated in highly experienced centres (6-8,72).

The importance of multidisciplinary board decisions and assessment of local resectability by an experienced thoracic surgeon cannot be stressed enough.

The recommendations of the EORTC consensus for stage III NSCLC for inclusion into clinical trials regarding T4 tumours are outlined in Table 3.

Current NCCN guidelines recommend surgery for resectable T4 N0–1 following neoadjuvant systemic treatment guided by biomarker testing, whereas unresectable T4 N0–1 and T4 N2 should receive definitive concurrent chemoradiotherapy (12). The American Society of Clinical Oncology (ASCO) guidelines recommend surgical resection after neoadjuvant treatment for T4 N0 tumours and surgery followed by adjuvant treatment for T4 N1 tumours (9). In contrast, European Society for Medical Oncology (ESMO) guidelines recommend surgery for T4 N0–2 NSCLC in case of T4 due to tumour size or an ipsilateral nodule in a separate lobe (10). Table 4 summarizes technical and prognostic factors across different extended resection scenarios in T4 tumours.

The role of extracorporeal life support (ECLS)

The introduction of extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) support in resections for NSCLC has allowed resectability of central T4 lesions previously considered inoperable and has enhanced the intraoperative management of hemodynamics and gas exchange (73). ECMO support allows peripheral cannulation and adequate oxygenation while avoiding full heparinization compared to CPB (74) and is less invasive when applied in veno-venous mode. ECMO-facilitated carinal and tracheal resections should be carried out in experienced centres with established protocols and expertise in advanced airway surgery. Patients with locally advanced NSCLC operated using intraoperative veno-venous ECMO (VV-ECMO) support show no significant difference in postoperative complications (P>0.99), hospital stay (P=0.23) or the level of circulating tumour cells prior and after the surgery compared to stage-matched patients operated without using VV-ECMO (75). ECMO-supported complex airway resections for patients with cT4 NSCLC are nowadays a feasible and safe surgery (76,77), while CPB is indicated in cases of atrial infiltration and necessity for open left atrial resection under cardioplegia, or in some cases of full-thickness aortic infiltration (78).

Central airway and carinal involvement

Carinal or distal tracheal involvement should be considered for surgery only when an R0 airway resection appears technically feasible while avoiding anastomotic tension. Most right-sided carinal resections are performed through a right posterolateral thoracotomy, whereas median sternotomy, clamshell or combined approaches may be useful for selected isolated carinal lesions or left-sided sleeve pneumonectomy. Ventilation can be achieved with cross-field ventilation, high-frequency jet ventilation, intermittent apnoea, or more specialized spontaneous-ventilation strategies; VV-ECMO is particularly useful when prolonged airway interruption or an unobstructed field is expected. Veno-arterial ECMO or CPB is reserved for situations requiring additional hemodynamic support or concomitant cardiac resection (74,76,77,79-81). Published series remain small but show that airway resection can be oncologically worthwhile in highly selected patients, with reported R0 rates of 80–100% and 5-year OS of roughly 21–56% (76,77,82). Beyond extracorporeal support, success depends on meticulous airway mobilisation, preservation of blood supply, minimisation of anastomotic tension, and avoidance of pneumonectomy whenever a parenchyma-sparing reconstruction is feasible (79-81).

Diaphragmatic invasion

Data on surgical outcome in cT4 tumours infiltrating the diaphragm remains limited since diaphragmatic invasion is relatively uncommon and often underrecognized before surgery. Superficial defects may be closed primarily whereas larger or full-thickness resections require prosthetic reconstruction. One retrospective analysis reported a 5-year OS of 30% with a postoperative mortality of 5% and an overall morbidity of 63% following extended pulmonary and diaphragm resections (83). Five-year OS appears to be significantly affected by both the depth of diaphragmatic tumour invasion (50% for superficial vs 0% for full-thickness invasion; P=0.03) and nodal status (43% in N0 patients vs 20% in N1–2 disease; P=0.03) (83).

SVC involvement

For SVC invasion, operative planning should first distinguish tangential from circumferential disease. Limited involvement can often be managed with side-clamping and primary or patch repair, whereas broader circumferential invasion generally requires replacement with an interposition graft and coordinated perioperative anticoagulation planning. The exact circumferential threshold varies by surgeon and anatomy, but partial repair is usually most appropriate when venous flow can be preserved without narrowing and full replacement when more than about one-third to one-half of the circumference is infiltrated (8,59,65). In cT4 tumours, SVC involvement, an R0 resection with complete SVC replacement has shown a 5-year OS of 29.4%, with a perioperative mortality of 7.7% (59). However, in this study, the 5-year OS was not significantly influenced by nodal status, with a 5-year OS of 19.6% in N2 disease compared to 37.5% in N0–1 patients, while patients with non-squamous cell cancer had a significantly better 5-year survival compared to those with squamous cell cancer (51% vs 12.2%; P=0.06). Additionally, patients with less than 50% of SVC infiltration are usually treated with direct suture or patch reconstruction, while an infiltration of more than 50% indicates a total replacement with a prosthesis. However, the extent of circumferential SVC infiltration (<50% or >50%) does not seem to significantly affect the 5-year OS, which was reported at 18.8% in both cases (65).

Aortic invasion

Aortic invasion requires meticulous preoperative imaging because operative strategy depends on the depth, circumferential extent and location of wall involvement. Contrast-enhanced CT with three-dimensional reconstruction is essential for assessing contact length, arch branch anatomy and potential landing zones if an endograft is contemplated. When the distinction between inflammatory adherence and true wall invasion remains uncertain, thoracic MRI with cine or gated sequences can add useful information regarding loss of the normal sliding plane and possible full-thickness infiltration (25,26,84-86). The choice of technique should follow the preoperative findings. Subadventitial dissection is reasonable only when a true dissection plane is present and wall infiltration appears limited. Endovascular stent-graft assisted resection is particularly attractive for descending aortic lesions with adequate proximal and distal landing zones, while direct cross-clamping, hybrid arch strategies or CPB may be required for more extensive arch disease or full-thickness invasion. Because pneumonectomy markedly increases morbidity, every effort should be made to preserve lung parenchyma when oncologically feasible (65,78,84-87). In carefully selected patients, aortic resection can provide meaningful survival. Recent series report 5-year OS of approximately 40–53%, with R0 resection and node-negative status consistently emerging as the dominant favourable factors (65,78,87).

Spinal invasion

Vertebral invasion remains one of the most demanding indications for extended resection and should be planned jointly with spine surgeons. Candidates are typically patients with limited vertebral body involvement, preserved neurologic function, no unreconstructable spinal canal disease, and a realistic chance of en bloc R0 resection after induction therapy (8,66). Open combined thoracic and posterior approaches remain the standard benchmark, but minimally invasive and hybrid strategies are beginning to enter this field. Hybrid VATS/posterior or fully thoracoscopic thoracic steps have been reported in highly selected patients to reduce chest wall trauma while preserving en bloc principles. These approaches should be viewed as extensions of mature open programs rather than substitutes for exposure, and should be limited to centres with established expertise in both complex thoracic oncology and spinal reconstruction (66,72,88). One of the largest retrospective series reports good surgical outcomes and a 31% 5-year OS in 54 patients with NSCLC invading the thoracic inlet and the spine (66).

Limitations of this review

This review has the inherent limitations of a narrative design. The selection of literature was not based on a formal systematic review process with risk-of-bias scoring, so selection and publication bias remain possible. In addition, the evidence base for extended resection in locally advanced NSCLC is dominated by retrospective single-centre series, heterogeneous definitions of resectability, historical cohorts spanning different staging systems and induction regimens, and strong referral bias toward high-volume expert institutions. Randomized controlled trials directly comparing surgery with definitive chemoradiotherapy/immunotherapy are lacking. Accordingly, many of the practical recommendations in this review should be interpreted as expert synthesis rather than high-level comparative evidence.

Future directions

Future progress will likely depend less on inventing new extended procedures and more on refining who truly benefits from them. Prospective registries and trial designs should distinguish anatomically resectable, borderline resectable and unresectable disease, integrate biologic response markers into resectability definitions and capture patient-reported and functional outcomes alongside survival. The role of treatment algorithm in borderline resectable patients, the role of conversion surgery and salvage surgery are currently under evaluation in prospective trials.

Technical innovation will continue, including hybrid operating rooms, three-dimensional planning, endovascular adjuncts, and selective minimally invasive or robotic components for complex resections. However, these tools should be judged by whether they improve patient selection, completeness of resection, recovery and continuity of multimodality therapy rather than by technical novelty alone.

Conclusions

Extended resections for locally advanced NSCLC are best understood as multimodal treatment strategy rather than a complex surgical intervention alone. The surgical expertise is apparently crucial to assess resectability taking tumour biology and functional reserve into account. Current guidelines recommend neoadjuvant treatment followed by surgery, also in advanced tumours if R0 resection seems achievable. Minimally invasive and hybrid techniques can reduce morbidity and hospital length of stay while maintaining oncologic results and allowing continuation of perioperative systemic therapies. Accurate preoperative planning, institutional experience and multidisciplinary cooperation are essential to achieve good outcomes.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Aimée J. P. M. Franssen, Peter B. Licht and Erik R. de Loos) for the series “Current Advances and Innovations in Surgical Lung Cancer Treatment” published in Translational Lung Cancer Research. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0262/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0262/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-2026-0262/coif). The series “Current Advances and Innovations in Surgical Lung Cancer Treatment” was commissioned by the editorial office without any funding or sponsorship. The authors have no other 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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