Vietnamese expert consensus on the diagnosis and multidisciplinary management of resectable non-small cell lung cancer

Introduction

Non-small cell lung cancer (NSCLC) is the most common histological subtype of lung cancer, accounting for approximately 85% of all lung malignancies (1,2). Lung cancer remains the leading cause of cancer incidence and cancer-related mortality worldwide. According to the Global Cancer Observatory (GLOBOCAN) 2024, there were approximately 2.63 million new lung cancer cases and 1.86 million lung cancer deaths globally, representing 12.8% of all new cancer cases and 19.1% of all cancer deaths, respectively (1). In Southeast Asia, lung cancer continues to contribute substantially to the regional cancer burden and remains a major challenge for health systems because of its high fatality and frequent late presentation (3,4).

In Vietnam, lung cancer represents a major national cancer burden and remains one of the leading causes of cancer-related death. The GLOBOCAN 2024 estimates reported 23,085 new lung cancer cases in Viet Nam, including 16,127 cases in males and 6,958 cases in females, underscoring the substantial burden of disease nationwide (5). Prognosis is strongly stage-dependent, and patients with resectable early-stage disease have a substantially better chance of long-term survival than those diagnosed at locally advanced or metastatic stages (6,7). Nevertheless, real-world evidence from Vietnam indicates that most patients with NSCLC are still diagnosed beyond the earliest curable stages, although improvements in earlier diagnosis, molecular testing, and overall survival have been observed over time (7).

The management of resectable NSCLC has changed rapidly over the past decade. Contemporary practice is no longer defined by surgery alone, but by increasingly individualized multimodality care integrating histopathology, tumour, node, metastasis (TNM) stage, molecular profiling, surgical planning, perioperative systemic therapy, and structured postoperative surveillance (2,6,8,9). The 2021 World Health Organization (WHO) Classification of Thoracic Tumours refined the pathological framework for lung cancer diagnosis (2), while the ninth edition of the Tumour, Node, Metastasis classification of the American Joint Committee on Cancer and Union for International Cancer Control (AJCC/UICC TNM 9th edition) (8) and the 2025 European Society for Medical Oncology (ESMO) Clinical Practice Guideline (6) further updated the approach to staging, risk stratification, resectability, perioperative treatment, adjuvant therapy, and follow-up. Moreover, randomised trials have reshaped the therapeutic landscape of resectable NSCLC, including neoadjuvant chemoimmunotherapy, perioperative immunotherapy, and biomarker-directed adjuvant therapy with osimertinib and alectinib (10-15).

In Vietnam, both the biological profile of NSCLC and the realities of clinical implementation differ from those of many Western populations. In the Vietnamese EARLY-EGFR study of resected early-stage non-squamous NSCLC, epidermal growth factor receptor (EGFR) mutations were identified in 51.0% of patients, with sensitizing alterations dominated by exon 19 deletions (49.0%) and exon 21 L858R mutations (33.3%). The prevalence was especially high among women (73.9%) and never-smokers (61.2%), and female sex remained strongly associated with EGFR positivity on multivariable analysis (16). This pattern is clinically important because it reinforces the need to move biomarker testing earlier in the treatment pathway rather than deferring molecular characterization until after surgery. In a setting where actionable driver alterations are common, delayed testing may lead to delayed or inappropriate perioperative treatment selection. Moreover, the implementation of modern lung cancer care in Vietnam remains heterogeneous, with marked differences in access to fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), endobronchial ultrasound (EBUS)-guided mediastinal staging, molecular testing, perioperative systemic therapy, and standardised multidisciplinary review across institutions and regions (7,17). Based on these considerations, a Vietnamese multidisciplinary expert process was undertaken not merely to restate international guidance, but to contextualize the best available evidence according to the realities of Vietnamese clinical practice.

Consensus development in resectable NSCLC

The Delphi method and its modified forms are increasingly used in health sciences when the evidence base is evolving, when randomised trials do not answer all operational questions, or when implementation requires structured multidisciplinary judgment (18,19). In oncology, and particularly in resectable NSCLC, this approach is useful for translating complex evidence into practical recommendations that can be applied consistently across different health-care settings.

In resectable NSCLC, many clinically important decisions are not determined by stage alone, but by the interaction between tumour biology, nodal burden, cardiopulmonary operability, pathology quality, diagnostic infrastructure, access to systemic therapy, and institutional expertise (6,9,17). Consensus development is therefore particularly valuable for areas in which strong trial evidence exists but local application remains variable, and for issues that require coordinated input from thoracic surgery, medical oncology, respiratory medicine, radiology, pathology, and nuclear medicine (9,17,18).

Study objectives and research questions

This project aimed to address evidence-to-practice gaps through a structured multidisciplinary expert process. The primary objectives were organized across four major domains: (I) to develop consensus statements on preoperative diagnosis and staging for potentially resectable NSCLC in Vietnam; (II) to develop consensus statements on surgery and postoperative surveillance after curative-intent resection; (III) to develop consensus statements on neoadjuvant and perioperative treatment, including patient selection and treatment sequencing; and (IV) to develop consensus statements on adjuvant treatment based on pathologic stage, biomarker profile, prior perioperative therapy, and treatment feasibility in Vietnam.

The specific research questions guiding this consensus

• What diagnostic, staging, and biomarker evaluation should be recommended before definitive treatment in potentially resectable NSCLC?
• What surgical principles and postoperative surveillance strategies should define curative-intent management?
• In which settings should neoadjuvant or perioperative systemic therapy be considered, and how should patients be reassessed before surgery?
• How should adjuvant treatment be selected according to pathologic stage, biomarker profile, prior therapy, and treatment feasibility in Vietnam?

By addressing these questions through a structured, modified Delphi-informed expert process, this project aimed to provide a practical, evidence-informed framework for the diagnosis and multidisciplinary management of resectable NSCLC in Vietnam. The goal was to improve consistency of care, promote appropriate use of modern perioperative and adjuvant therapies, and reduce inter-institutional variation while remaining aligned with contemporary international standards.

We present this article in accordance with the ACCORD reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0852/rc) (20).

Methods

Study design

This study employed a structured, modified Delphi-informed methodology to develop Vietnamese multidisciplinary consensus statements for the diagnosis and management of resectable NSCLC in Vietnam (21,22). The process was undertaken between August 2025 and January 2026 and comprised seven stages: a scoping meeting, a baseline practice survey, initial draft development, expert review for parts 1 and 2, post-meeting written feedback and recirculation, a multidisciplinary consensus meeting for parts 3 and 4, and final editorial harmonization and consolidation. In contrast to a classical Delphi process, the present project did not rely on repeated fully anonymous questionnaire rounds across all sections. Instead, it combined multidisciplinary meetings, written feedback, recirculation, and formal voting to finalize the consensus statements. The consensus protocol was approved by the Institutional Review Board of Thong Nhat Hospital, Ho Chi Minh City, Vietnam (approval No. 92/2025/CN-BVTN-HĐĐĐ, dated 27 June 2025). This project involved expert consultation only and did not include patient participation or the collection of patient-level data. Participation was voluntary. All formal ratings, voting, and written feedback were handled confidentially, and the manuscript reports aggregated results only.

Organizing structure and expert participation

The consensus process was coordinated by a steering and writing group on behalf of the participating professional societies involved in oncology and thoracic surgery in Vietnam. The initiative was led principally by the Association of Cardiovascular and Thoracic Surgery of Ho Chi Minh City in collaboration with the Ho Chi Minh City Cancer Society. The steering and writing group was responsible for planning the workflow, preparing draft materials, synthesizing evidence summaries, collating comments, and harmonizing revisions. The expert panel consisted of partially overlapping multidisciplinary participants across the three main meetings. For each stage, invitations, attendance, participation format, specialty, and practice setting were documented. The full list of participating experts, including their specialties and institutional affiliations, is provided in Appendix 1.

Expert selection and recruitment

Experts were selected through purposive multidisciplinary sampling. Representation was sought from specialties involved in the care of resectable NSCLC, including thoracic surgery, respiratory medicine, medical oncology, pathology, nuclear medicine, and radiation oncology. Selection was based on clinical experience in lung cancer management, involvement in multidisciplinary care, and relevance to the scope of the project. The panel primarily comprised senior clinicians with substantial experience in NSCLC management, and many had more than 20 years of practice experience. Experts were recruited through direct invitation by the organizing societies and the coordinating group. Invitations were distributed through professional networks and direct communication, and the recruitment process was centrally coordinated by the organizing group.

Confidentiality and consensus procedures

Anonymity was not maintained during live multidisciplinary meetings because direct discussion was considered necessary to clarify clinically complex issues, address wording disagreements, and resolve implementation-sensitive points. However, post-meeting written feedback and formal voting records were handled confidentially by the coordinating group and are reported in aggregated form only (23). The steering and writing group facilitated document development, evidence synthesis, statement drafting, and revision tracking. Members of the steering and writing group did not participate in formal voting.

Consensus workflow

Phase 1: scoping meeting

The first meeting, held on 10 August 2025, functioned as a scoping and framework-development meeting. Its purpose was to define the scope of the consensus document, identify the major domains to be addressed, discuss the overall recommendation structure, and determine the subsequent workflow. This meeting also initiated development of the statement bank, recommendation framework, and evidence-brief plan. Phase 1 did not have a formal statement-by-statement voting round; rather, it established the conceptual architecture of the project and generated the agenda for the next stages.

Phase 2: baseline practice survey

After the scoping meeting, a baseline practice survey was circulated to participating physicians to gather information on real-world practice patterns, service availability, institutional resources, and areas of variation in current NSCLC management in Vietnam. The survey was intended as a descriptive practice-mapping exercise rather than a formal consensus-rating instrument. It did not use a structured Likert agreement scale. Responses were summarized descriptively using counts and percentages. The findings informed the prioritization and contextual framing of the draft recommendations and statements.

Phase 3: initial draft development

Draft statements were prepared by the steering and writing group using three main inputs: (I) the scoping meeting output; (II) the baseline survey findings; and (III) a targeted review of current international evidence and guideline documents. The draft was organized into four major sections: preoperative diagnosis and staging, surgery and postoperative surveillance, neoadjuvant or perioperative therapy, and adjuvant therapy. Each proposed statement was paired with an evidence summary and an initial recommendation class. At this stage, statement wording was framed either more directly or more conditionally depending on the strength and consistency of evidence, degree of expert agreement, and anticipated feasibility of implementation across Vietnamese centres.

Phase 4: expert review meeting for Parts 1 and 2

A topic-specific expert meeting was subsequently held on 16 November 2025 to discuss Part 1 (diagnosis and staging) and Part 2 (surgery and postoperative surveillance). Draft statements were reviewed in detail, with discussion focusing on scientific clarity, wording, applicability in Vietnam, the legal and practical implications of directive language, and the need to preserve flexibility where implementation might depend on variation in infrastructure or expertise across centres.

Phase 5: post-meeting written feedback, electronic recirculation, and formal voting

Following the meeting covering Parts 1 and 2, the revised draft was returned to the participating experts for further written review. Additional comments were incorporated, and the wording of the statements was refined to improve scientific accuracy, contextual relevance, and interpretability. On 23 November 2025, the revised wording and proposed recommendation classes for the statements in Parts 1 and 2 were electronically recirculated to the same experts who had participated in the meeting for formal statement-level voting. Experts recorded their agreement or disagreement with each statement, and completed ratings were returned confidentially to the coordinating group.

Phase 6: consensus meeting and formal voting for Parts 3 and 4

A subsequent multidisciplinary consensus meeting was held on 27 December 2025 to address Part 3 (neoadjuvant or perioperative treatment) and Part 4 (adjuvant treatment), while also revisiting unresolved or cross-cutting issues from earlier sections where necessary. All statements in Parts 3 and 4 underwent formal statement-level voting during this meeting. Supporting evidence was revisited during discussion, and the final wording of the statements, together with their classes of recommendation, was agreed upon after structured deliberation and formal voting.

Phase 7: final editorial harmonization and consolidation

After the second content meeting, the consolidated draft was circulated again for final written comments. These comments were incorporated into a harmonized final version by the writing and coordination team under the oversight of the scientific leadership. This final stage, completed in January 2026, focused on language harmonization, editorial standardization, completion of the audit trail, revision tracking, and final manuscript consolidation.

Across the different phases, draft items were circulated in written form before and after the meetings. Live multidisciplinary discussions were not anonymous, whereas written feedback and formal voting records were handled confidentially by the coordinating group and are reported only in aggregated form. The overall workflow is summarized in Figure 1.

Figure 1 Flow diagram of the modified Delphi-informed expert consensus process for the Vietnamese resectable NSCLC consensus statements. The process comprised seven stages, beginning with a scoping meeting, baseline practice survey, and initial draft development, followed by topic-specific expert review, written feedback and recirculation, formal electronic voting for Parts 1 and 2, formal voting for Parts 3 and 4 during the multidisciplinary consensus meeting, and final harmonization. Part 1, preoperative diagnosis and staging; Part 2, surgery and postoperative surveillance; Part 3, neoadjuvant and perioperative treatment; and Part 4, adjuvant treatment. NSCLC, non-small cell lung cancer.

Evidence review and statement development

The consensus statements were developed on the basis of the strength and relevance of the available evidence. The steering and writing group reviewed major classification and staging documents, current international guidelines, expert consensus papers, and pivotal clinical trials relevant to resectable NSCLC. Priority was given to the most recent versions available at the time of drafting, while earlier landmark references were retained when they remained directly relevant to current clinical practice. Core references included the 2021 WHO Classification of Lung Tumours (24), the AJCC/UICC TNM 9th edition staging framework (8,25), National Comprehensive Cancer Network (NCCN) and ESMO guidance for early and locally advanced NSCLC (6,26), and International Association for the Study of Lung Cancer (IASLC) recommendations for pathologic assessment after neoadjuvant therapy (27). For neoadjuvant, perioperative and adjuvant treatment recommendations, the group also considered key phase III studies, including CheckMate 816 (11), AEGEAN (12), KEYNOTE-671 (13), CheckMate 77T (14), ADAURA (10), ALINA (15), IMpower010 (28), and PEARLS/KEYNOTE-091 (29), as well as meta-analyses (30).

For each topic, the available evidence was considered alongside local implementation issues in Vietnam, including access to FDG-PET/CT, invasive mediastinal staging, biomarker testing, multidisciplinary review, perioperative systemic therapy, pathology standardization, and follow-up resources. Where evidence was robust and broadly consistent across major guidelines and clinical trials, statements were worded more directly. Where evidence remained limited, evolving, or strongly dependent on resource availability and local feasibility, statements were deliberately phrased more conditionally.

Recommendation grading

Each draft statement was initially assigned a proposed class of recommendation by the steering and writing group on the basis of the available evidence, consistency across major international guidelines, clinical relevance, expert judgment, and feasibility within Vietnamese practice. The wording and proposed recommendation classes of statements submitted to formal voting were reviewed through expert deliberation and formal voting during the consensus process.

The panel assigned classes of recommendation without separate levels of evidence. Each class was designed to reflect the strength, direction, and practical applicability of the recommendation within the Vietnamese clinical context, taking into account the available evidence, consistency across major international guidelines, expert judgment, and local feasibility. Detailed supporting evidence for each statement is discussed in the corresponding statement-specific rationale. The grading system applied in this consensus was adapted from the framework for classes of recommendation used by the European Society of Cardiology (31), with contextual refinement through expert discussion. The recommendation classes used in this document are summarized in Table 1.

Definition of consensus

For all final statements, consensus was predefined as agreement of at least 75%, consistent with commonly used thresholds in consensus-method studies and Delphi-based research (32). This threshold was selected to indicate substantial agreement while allowing limited disagreement within a multidisciplinary panel. Statements that met consensus could still undergo minor wording refinement during subsequent recirculation, provided that the intended recommendation was not materially changed. Statements that did not initially reach the predefined threshold, or that prompted important concerns regarding wording, scope, feasibility, or interpretation, were revised by the steering and writing group and re-evaluated through subsequent discussion and/or written recirculation before finalization. After completion of the formal consensus process, selected statements underwent post-consensus manuscript revisions to improve clarity, scope, structure, or alignment of recommendation class with the supporting evidence.

Statistical analysis

All statistical analyses were performed in Microsoft Excel. For each statement, the agreement rate was determined as the percentage of experts in agreement among all experts who participated in the corresponding voting round. Disagreeing votes were retained in the denominator, and any accompanying comments were reviewed during final editorial harmonization.

Results

Thirty-five physicians completed the baseline practice survey. Respondents were predominantly thoracic surgeons, and variation was observed in institutional surgical volume, preoperative imaging and biomarker testing, multidisciplinary team (MDT) practice, and post-treatment assessment. Routine MDT practice was reported by 80.0% of respondents, whereas routine pCR/MPR and minimal residual disease (MRD) assessments were reported by 31.4% and 25.7%, respectively. Selected quantitative findings are presented in Appendix 2.

Twenty experts were invited to the scoping meeting, of whom 19 participated (95%). Twenty experts were invited to the meeting covering Parts 1 and 2, and all participated (100%). All 20 experts subsequently returned valid ratings for each statement in Parts 1 and 2 (100% voting response), with agreement ranging from 90% to 100%. For the meeting covering Parts 3 and 4, 25 experts were invited and 17 participated (68%); all 17 participants returned valid votes (100% voting response), with agreement ranging from 82% to 100% (Table 2).

Across the three meeting rosters, 32 unique experts were identified after deduplication. The panel was multidisciplinary, with strong representation from thoracic surgery (40.6%) and medical oncology (25.0%), together with respiratory medicine, pathology, nuclear medicine, and radiation oncology. Geographic representation was concentrated in Ho Chi Minh City (53.1%) and Hanoi (40.6%), with additional representation from Da Nang (6.3%) (Table 3).

The final document comprised 35 consensus statements across four domains: 7 statements on diagnosis and preoperative staging, 8 statements on surgery and postoperative surveillance, 12 statements on neoadjuvant and perioperative treatment, and 8 statements on adjuvant treatment. All statements submitted to formal voting met the predefined consensus threshold, and no abstentions were recorded. During final manuscript development, selected statements were subsequently refined in wording, scope, structure, or recommendation class. Appendix 3 provides a consolidated summary of all final consensus statements, recommendation classes, original statement-level agreement percentages, and relevant post-consensus revisions.

Part 1: consensus on preoperative diagnosis and staging

Statement 1: NSCLC should be anatomically staged according to the AJCC/UICC TNM 9th edition. However, eligibility for perioperative or adjuvant treatment should be determined according to the clinicopathologic criteria and TNM edition used in the relevant pivotal trials, together with applicable regulatory indications [Class I].

Accurate anatomical staging remains fundamental to prognostic assessment, treatment planning, and multidisciplinary decision-making in resectable NSCLC. The AJCC/UICC TNM 9th edition provides the current framework for anatomical staging and incorporates revisions intended to improve prognostic stratification (8,25). External validation has also demonstrated improved discriminatory performance of the 9th edition compared with the 8th edition in surgically treated stage I–III NSCLC (33).

Importantly, the AJCC/UICC TNM 9th edition is used in this consensus for current anatomical staging and should not be used to retrospectively redefine eligibility for therapies evaluated under earlier TNM editions. Pivotal perioperative and adjuvant trials enrolled patients according to the TNM edition and clinicopathologic eligibility criteria specified in their original protocols. For example, CheckMate 816 enrolled patients with stage IB (tumours ≥4 cm)–IIIA disease according to the seventh edition, whereas AEGEAN, KEYNOTE-671, and CheckMate 77T used eighth-edition staging for their respective resectable populations (11-14). Likewise, ADAURA and ALINA enrolled patients according to seventh-edition stage definitions (10,15). Accordingly, therapeutic eligibility in this consensus is expressed using the original trial-defined criteria, including tumour size and nodal status where relevant, together with the corresponding TNM edition and applicable regulatory indications, rather than being inferred solely from ninth-edition stage groups.

Statement 2: preoperative contrast-enhanced chest CT should be performed in all patients for anatomic staging. FDG-PET/CT should also be obtained, when available, in patients with potentially curative clinical stage IB–III disease or when nodal or distant staging may alter management. Invasive mediastinal staging should be considered in patients with suspicious mediastinal nodes or an increased risk of occult N2 disease, including central tumours, clinical N1 disease, or tumours >3 cm. EBUS/EUS-guided sampling should generally be the initial approach, with surgical staging considered when endosonographic findings are negative but suspicion remains high [Class I].

Accurate preoperative staging in potentially resectable NSCLC requires complementary anatomic and metabolic imaging, but imaging alone is not sufficiently reliable for treatment-defining decisions. Contrast-enhanced chest CT provides the anatomical basis for evaluating the primary tumour and nodal enlargement, whereas FDG-PET/CT improves detection of occult nodal and distant metastases and is particularly relevant when nodal or distant staging may alter management (6,26). However, FDG-PET/CT does not reliably distinguish malignant nodal uptake from inflammatory or granulomatous uptake. A meta-analysis of integrated FDG-PET/CT for mediastinal staging reported pooled sensitivity and specificity of 0.76 and 0.88, respectively, indicating useful but still imperfect diagnostic performance (34).

Pathologic mediastinal staging remains important when nodal status may alter treatment strategy and should not be restricted to patients with CT-enlarged or FDG-PET/CT-positive mediastinal nodes. Invasive mediastinal staging should also be considered in patients with central tumours, clinical N1 disease, or tumours >3 cm, including when mediastinal FDG-PET/CT findings are negative (35). The European Society of Thoracic Surgeons (ESTS) guideline identifies endosonography with EBUS or endoscopic ultrasound (EUS)-guided sampling as the preferred initial invasive approach when available. When endosonographic sampling is negative but clinical or radiologic suspicion remains high, surgical mediastinal staging should be considered to reduce the risk of understaging (35). This stepwise strategy is also consistent with more recent thoracic oncology reviews and multidisciplinary consensus practice (9,36).

Expert discussion highlighted that FDG-PET/CT, EBUS, mediastinoscopy, and operator experience are not uniformly distributed across institutions, while inflammatory and post-infectious thoracic disease may complicate radiologic interpretation. In a tuberculosis-endemic setting, FDG-PET/CT for mediastinal staging showed sensitivity of 0.87 but specificity of only 0.45 when any nodal uptake was considered positive; even at a higher standardized uptake value threshold, specificity remained limited at 0.79 (37). These findings reinforce the importance of integrating imaging findings with clinical risk factors and tissue confirmation when mediastinal staging may alter treatment strategy. The persistent risk of occult pathological N2 disease despite apparently adequate clinical staging, with reported prevalence ranging from 7% to 21% in the Malaysian surgical consensus review, further supports a selective, risk-based approach to invasive mediastinal staging rather than reliance on imaging findings alone (9).

Statement 3: brain magnetic resonance imaging (MRI) should be performed before surgery in patients with clinical stage II or higher NSCLC. If MRI is not feasible, contrast-enhanced brain CT may be used as an alternative [Class IIa].

Occult intracranial metastasis may alter TNM stage, change treatment intent, and preclude upfront curative resection. Pre-treatment brain imaging therefore has direct implications for the management of potentially resectable NSCLC. Current international guidance supports central nervous system (CNS) staging in patients with stage II or higher disease who are being considered for curative-intent treatment. The 2025 ESMO guideline recommends brain imaging from stage II onward and recognizes contrast-enhanced brain MRI as the preferred modality, while the NCCN guideline likewise includes brain MRI in pretreatment evaluation for stage II–III disease, with contrast-enhanced CT accepted when MRI is not feasible (6,26).

Brain MRI remains the preferred test because of its higher sensitivity for small and asymptomatic brain metastases. The practical importance of intracranial staging is supported by evidence summarized in the Malaysian multidisciplinary consensus paper, which noted that brain metastases are present in approximately 20% of patients at diagnosis and may develop in up to 40% during the course of disease. Detection of occult brain involvement in a patient otherwise considered for surgery may redirect management toward systemic treatment or multimodality therapy rather than immediate thoracic resection (9).

Expert discussion in the Vietnamese panel showed some variation in the preferred threshold for routine brain imaging. Some experts supported imaging from stage IB, whereas others favoured prioritizing stage III disease and using a more selective approach in stage II. The final wording based on stage II or higher provides a balanced position that remains aligned with the strongest available evidence while avoiding overextension of routine imaging into earlier-stage groups where guidance is less consistent. Panel discussion suggested that MRI is available in many centres and should be preferred whenever possible; however, a rigid MRI-only requirement may reduce feasibility in institutions where scheduling delays, contraindications, or workflow limitations affect access. Retaining contrast-enhanced brain CT as an alternative preserves clinical practicality without weakening the overall staging principle. For that reason, the statement supports MRI as the preferred modality while allowing brain CT as an acceptable fallback when MRI cannot be performed in a timely and appropriate manner (6,9,26).

Statement 4: in patients with suspected stage I–III NSCLC, pathological confirmation should be obtained before treatment whenever feasible, particularly before systemic therapy or nonsurgical definitive treatment. However, in medically operable patients with a highly suspicious, technically resectable lesion, surgery may provide both diagnosis and definitive treatment when preoperative biopsy is unsafe, technically unsuccessful, or unlikely to change management. Histopathological diagnosis should follow the 2021 WHO classification [Class I].

Tissue diagnosis is required not only to confirm malignancy, but also to establish histologic subtype accurately and to preserve adequate material for subsequent biomarker testing when indicated. This point is clinically important because NSCLC is a heterogeneous disease entity rather than a single pathologic category. NSCLC accounts for approximately 80% to 85% of all lung cancers, with adenocarcinoma representing about 40% and squamous cell carcinoma about 20% to 30% of cases, and these subtypes may differ in diagnostic approach, biomarker profile, and downstream treatment implications (38).

The 2021 WHO Classification of Thoracic Tumours continues to recommend a morphology-first approach, with immunohistochemistry used selectively when necessary, particularly in small biopsy and cytology specimens (24). This framework is especially relevant in resectable disease, where accurate subclassification at the time of initial diagnosis may influence not only surgical planning but also the interpretation of biomarker results and eligibility for perioperative or adjuvant systemic treatment. Accordingly, pathological confirmation based on histomorphology, supplemented by immunohistochemistry when required, should be regarded as a core component of pre-treatment evaluation in suspected stage I–III NSCLC, whenever feasible (6,24).

The expert panel also considered the recommendation particularly relevant in the Vietnamese setting, where preoperative tissue acquisition may be challenging in some patients because of underlying chronic inflammatory lung disease, post-tuberculosis structural change, chronic obstructive pulmonary disease, necrotic lesions, or technically difficult tumour location. Under such circumstances, limited or non-representative samples may reduce diagnostic confidence and may compromise the ability to complete subsequent biomarker testing. For that reason, preoperative biopsy should be optimized whenever feasible, with close coordination among clinicians performing tissue acquisition, radiologists, surgeons, and pathologists to maximize diagnostic yield and preserve tissue adequacy for histologic classification and further testing. However, preoperative tissue confirmation should not be considered an absolute requirement in every technically resectable case. In a medically operable patient with a highly suspicious, technically resectable lesion, proceeding directly to surgery may occasionally be appropriate when biopsy is unsafe, technically unsuccessful, or unlikely to change management. In such circumstances, surgery may provide both definitive diagnosis and curative-intent treatment (39).

Statement 5: testing for EGFR mutation, anaplastic lymphoma kinase (ALK) rearrangement, and programmed death ligand 1 (PD-L1) expression should be performed on the preoperative biopsy specimen to inform multimodality treatment planning. If preoperative testing cannot be completed, biomarker testing should be performed on the surgical specimen to guide adjuvant treatment [Class I]. Next-generation sequencing should be considered when feasible [Class IIb].

Predictive biomarker assessment is integral to treatment planning in resectable NSCLC because EGFR mutation, ALK rearrangement, and PD-L1 expression may directly influence perioperative and adjuvant treatment selection (6,38,40). The clinical relevance of early testing is supported by contemporary perioperative immunotherapy trials and by the established roles of adjuvant osimertinib and alectinib in EGFR-mutated and ALK-positive disease, respectively (10,12,15,30).

Vietnamese data further support early molecular characterization. The EARLY-EGFR study reported EGFR mutations in 51.0% of patients with resected early-stage non-squamous NSCLC, indicating that actionable alterations are common in this population (16). As a result, the expert panel considered EGFR, ALK, and PD-L1 the minimum core biomarker set for perioperative decision-making. Broader multigene testing, including next-generation sequencing, may be considered when tissue adequacy, laboratory capacity, turnaround time, and cost permit.

Statement 6: to determine surgical candidacy, patients should undergo detailed staging according to the AJCC/UICC TNM 9th edition together with stepwise cardiopulmonary functional assessment. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) should be performed as baseline assessments, followed, when indicated, by predicted postoperative lung function and exercise testing. Cardiopulmonary exercise testing (CPET) should be reserved for patients with impaired functional reserve, significant cardiopulmonary disease, or otherwise uncertain operative risk. Where these investigations are not available, alternative assessments may be used according to institutional resources and local practice [Class I].

Preoperative decision-making should address two separate but complementary questions. Technical resectability concerns whether an R0 resection is reasonably achievable after adequate staging and multidisciplinary assessment (41-43). Medical operability concerns whether the patient can tolerate the proposed operation with acceptable perioperative risk and adequate postoperative function; it should be assessed on the basis of cardiopulmonary reserve, relevant comorbidities, performance status, and anticipated postoperative functional capacity (6,44). Overall surgical candidacy requires both technical resectability and medical operability. Anatomical staging should follow the current TNM framework (6,8), whereas physiological assessment should proceed stepwise using spirometry and DLCO, predicted postoperative lung function, exercise testing, and CPET when indicated (44). Patients with known or suspected cardiovascular disease should undergo appropriate cardiology evaluation before curative-intent treatment, with further cardiac investigations performed as clinically indicated (44).

Vietnamese practice adds an important implementation consideration because preoperative assessment capacity is not uniform across institutions. Expert review indicated that DLCO, CPET, ventilation-perfusion studies, and other advanced predictive tools are not consistently available across all centres. For that reason, the consensus was framed around a stepwise rather than universal testing pathway. Spirometry and DLCO should form the baseline physiological assessment. Predicted postoperative forced expiratory volume in 1 second (FEV₁) and DLCO should be assessed when further estimation of postoperative functional reserve is required. Low-technology exercise testing may be used for additional functional risk stratification, while CPET should be reserved for patients with reduced predicted postoperative lung function, poor performance on low-technology exercise testing, significant cardiopulmonary disease, or otherwise uncertain operative risk. Where advanced investigations are not available, validated alternative assessments may be used according to institutional resources and local practice (6,9,42).

Preoperative evaluation in Vietnam also needs to account for the background burden of respiratory and cardiovascular comorbidity, including chronic obstructive pulmonary disease, prior pulmonary tuberculosis or post-tuberculosis structural lung damage, coronary artery disease, and other conditions that may increase perioperative risk. Under such circumstances, the key question is not only whether the tumour is technically resectable, but also whether resection can be performed with acceptable perioperative risk and adequate postoperative functional reserve. Borderline cases are particularly relevant in this context, because prediction of postoperative reserve and multidisciplinary review may alter the treatment strategy. Expert discussion further indicated that the ability to perform lung cancer surgery safely and appropriately also depends on institutional diagnostic capability, perioperative support, and surgical expertise. As a result, the feasibility of safely delivering surgery may vary across centres even in patients with similar tumour stage and baseline fitness. Table 4 summarizes the preoperative diagnostic and assessment workup for potentially resectable NSCLC, adapted from the 2025 ESMO guidelines (6) and the 2025 European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS) guideline on fitness for curative-intent treatment of lung cancer (44), and refined by expert consensus for local practice.

Statement 7: MDT discussion should be applied to all patients with clinical stage II or higher NSCLC before surgery to guide multimodality treatment planning. For patients with clinical stage IB disease, MDT discussion should be considered when staging, resectability, or treatment strategy is uncertain. At a minimum, MDT discussion should be ensured for complex or borderline cases [Class IIa].

Multidisciplinary evaluation supports coordinated staging and multimodality treatment selection in resectable NSCLC, particularly when treatment sequencing is complex (6,9). A 2023 systematic review and meta-analysis found that MDT management was associated with improved overall survival, with a pooled hazard ratio of 0.60, as well as shorter time to treatment and a higher proportion of complete staging (45). In a large registry-based study, the propensity-matched 5-year survival rate was 33.6% among patients managed through an MDT model compared with 23.0% among those managed through a traditional model, with an adjusted hazard ratio of 0.65 (46). Although much of the evidence remains observational, the overall direction consistently supports improved staging, care coordination, and treatment selection through multidisciplinary management (45-47).

In the Vietnamese context, MDT discussion should be applied to patients with clinical stage II or higher disease before surgery whenever feasible because treatment planning is increasingly individualized and may involve multimodality care. For patients with clinical stage IB disease, routine preoperative MDT discussion may not be necessary when staging is complete and upfront resection is clearly appropriate; however, it should be considered when staging, resectability, or treatment strategy is uncertain. Universal formal MDT review may not always be feasible in high-volume centres. Therefore, MDT discussion should at minimum be ensured for complex, borderline, locally advanced, or other potentially multimodality cases, with hybrid or online models used where appropriate.

Part 2: consensus on surgery and postoperative surveillance

Statement 8: surgery is indicated for medically operable patients with technically resectable NSCLC. Lobectomy is the standard surgical treatment for NSCLC. Surgery should achieve an R0 resection, defined as microscopically negative margins together with systematic lymph node dissection or selective nodal dissection [Class I].

Surgery remains the cornerstone of treatment for medically operable patients with technically resectable NSCLC. Medical operability is addressed in Statement 6; the present statement focuses on technical resectability. For this consensus, technical resectability means that, after adequate staging, an experienced thoracic surgeon within an MDT considers an R0 resection reasonably achievable. TNM stage alone is insufficient to determine resectability because it does not fully capture the distribution, bulk, or invasiveness of nodal disease, the specific structures invaded by a T4 tumour, or the technical complexity of achieving complete resection (43,48).

Among patients with N2 disease, single-station, non-bulky, non-invasive involvement is the pattern most consistently regarded as potentially resectable (41,43). Multistation N2 disease is less often considered resectable and should not automatically lead to a surgery-based strategy; selected non-bulky, non-invasive cases may nevertheless be considered after individualized assessment by an experienced thoracic surgeon within an MDT (43). Bulky or invasive N2 disease and N3 disease are generally considered unresectable (43). For T4 disease, technical resectability depends on the specific structure involved and on whether an en bloc R0 resection, with reconstruction where necessary, can be achieved with acceptable risk in an experienced centre; therefore, T4 classification alone should not determine resectability (41-43).

Lobectomy remains the standard reference operation for most medically fit patients with conventional resectable NSCLC because it continues to offer the most established balance between oncologic control and postoperative function. In the Lung Cancer Study Group randomised trial, 247 eligible patients with peripheral T1N0 NSCLC were analysed; limited resection was associated with a 75% increase in recurrence, a tripling of local recurrence, and a 30% increase in overall death rate compared with lobectomy (49). Although more recent randomised trials have shown that sublobar resection may be acceptable in carefully selected small peripheral node-negative tumours, those data apply to a narrower population and do not displace lobectomy as the general standard for most resectable cases (50,51). Accordingly, lobectomy should still be regarded as the default surgical procedure unless tumour characteristics or patient-related factors justify a more limited resection.

Statement 9: when the goal is an R0 resection, minimally invasive thoracic surgery, particularly video-assisted thoracoscopic surgery (VATS) and, where appropriate, robotic-assisted thoracic surgery (RATS), should be preferred in suitable patients because it reduces postoperative morbidity without compromising oncologic adequacy in experienced hands [Class IIa].

Minimally invasive thoracic surgery has become the preferred approach for many patients with resectable NSCLC because postoperative recovery is generally better than with thoracotomy while oncologic outcomes remain acceptable in appropriately selected cases. In the VIOLET randomised trial, VATS lobectomy was associated with better physical function at 5 weeks, less pain, shorter hospital stay, fewer postoperative complications, and fewer readmissions than open lobectomy, without evidence of inferior short-term oncologic outcome (52). These findings support preference for a minimally invasive approach when the planned operation can still achieve a safe and oncologically sound resection (6).

The benefit of minimally invasive surgery is operator-dependent and should not be attributed to the surgical platform alone. Adequate margins, safe hilar and vascular dissection, and appropriate lymph node assessment remain essential regardless of whether surgery is performed by VATS, RATS, or thoracotomy. Current guidance also supports minimally invasive resection in appropriately selected patients while emphasizing preservation of oncologic principles and the importance of surgical expertise (6). Evidence comparing robotic and thoracoscopic approaches suggests that robotic surgery may improve the extent of lymph node assessment in some settings, but clear superiority in overall perioperative outcomes has not been consistently demonstrated. In the ROMAN randomised study, robotic surgery was not superior to VATS for perioperative complications, conversion, or length of stay, although more lymph node stations were sampled in the robotic arm (53). The expert panel therefore supported minimally invasive surgery as the preferred approach in appropriately selected resectable NSCLC.

Statement 10: sublobar resection may be considered (I) in appropriately selected patients with a peripheral tumour measuring 2 cm or less, appropriate tumour imaging characteristics, and carefully confirmed node-negative disease, and/or (II) in patients who are not suitable candidates for lobectomy because of limited pulmonary reserve or substantial comorbidity. When a sublobar approach is selected, an adequate parenchymal margin, preferably at least 2 cm or at least equivalent to the tumour diameter, should be achieved together with appropriate intraoperative hilar and mediastinal nodal assessment. Anatomical segmentectomy is generally preferred when technically feasible, preferably in centres with adequate technical capability to ensure R0 resection and after MDT discussion [Class IIa].

The role of sublobar resection in resectable NSCLC has expanded in recent years, but the modern randomized evidence applies to carefully selected patients. In CALGB 140503, sublobar resection was non-inferior to lobectomy for disease-free survival in patients with peripheral NSCLC with a solid component measuring 2 cm or less and pathologically confirmed node-negative hilar and mediastinal disease (50). In the Japanese randomized trial (JCOG0802/WJOG4607L), segmentectomy was evaluated in patients with peripheral clinical stage IA NSCLC measuring 2 cm or less and a consolidation-to-tumour ratio greater than 0.5 on thin-section CT; 5-year overall survival was 94.3% with segmentectomy versus 91.1% with lobectomy, while relapse-free survival was similar (51). These findings support sublobar resection as an acceptable option in appropriately selected small peripheral node-negative tumours and highlight the importance of tumour imaging characteristics and rigorous nodal assessment in patient selection.

However, sublobar resection should not be interpreted as a universal replacement for lobectomy. In JCOG0802/WJOG4607L, local recurrence was higher after segmentectomy than after lobectomy, at 10.5% versus 5.4% (51). Adequate parenchymal margins and intraoperative nodal assessment are therefore important components of oncologically appropriate sublobar resection. In CALGB 140503, the protocol recommended a parenchymal margin of 2 cm or a margin equivalent to the tumour diameter for wedge resection, and randomization occurred only after pathologic confirmation of node-negative hilar and mediastinal disease (50,54). Importantly, CALGB 140503 allowed both segmentectomy and wedge resection. In the subsequent post hoc analysis, 5-year disease-free, overall, and lung cancer-specific survival did not differ significantly between segmentectomy and wedge resection, and locoregional recurrence was numerically but not significantly higher after wedge resection (54). Thus, although anatomical segmentectomy is generally preferred when technically feasible for oncologic reasons, the available randomized evidence does not establish its superiority over wedge resection in all eligible patients. In Vietnam, where surgical expertise, staging quality, and institutional resources are not uniform across centres, individualized decision-making and multidisciplinary review remain appropriate, particularly in borderline cases or when sublobar resection is considered because of limited physiologic reserve or substantial comorbidity.

Statement 11: curative-intent pulmonary resection, whether by lobectomy or segmentectomy, should include appropriate lymph node dissection or sampling. This may be achieved through systematic lymph node dissection or systematic nodal sampling; at minimum, at least three mediastinal nodal (N2) stations, including the subcarinal station when anatomically appropriate, and at least one hilar or intrapulmonary nodal (N1) station should be sampled or dissected. When segmentectomy is performed, the same minimum hilar and mediastinal nodal assessment should apply [Class IIa].

Systematic nodal assessment is an essential component of curative-intent surgery for NSCLC because the quality of resection depends not only on removal of the primary tumour, but also on accurate pathological nodal staging (55). Inadequate nodal evaluation may lead to understaging, reduce confidence in postoperative risk stratification, and potentially affect decisions regarding adjuvant treatment (56). This recommendation is also consistent with current international guidance. The Commission on Cancer standard for curative-intent pulmonary resection specifies assessment of at least one N1 station and three distinct N2 stations (55,56), while recent thoracic oncology guidance and IASLC-based standards similarly support examination of at least three mediastinal stations, including the subcarinal station, as part of complete resection and accurate staging (6). In a randomised trial of rigorously staged patients with early-stage NSCLC, complete mediastinal lymph node dissection did not improve overall or disease-free survival compared with systematic mediastinal sampling after predefined nodal assessment had already been performed (57). These findings suggest that the key principle is not routine complete lymph node dissection in every case, but rather appropriate and systematic nodal evaluation, which may be achieved through systematic lymph node dissection or systematic nodal sampling. Accordingly, the recommendation should not be interpreted as mandating complete lymph node dissection for all patients. Expert discussion supported this statement because it defines a practical and verifiable minimum standard for nodal sampling or dissection that should also be maintained when segmentectomy is performed, particularly given variation in surgical practice, pathology workflows, and healthcare facility resources.

Statement 12: postoperative follow-up should be conducted by dedicated lung cancer specialists, such as thoracic surgeons, medical oncologists, or pulmonologists. Chest CT should be performed approximately every 6 months during the first 2 years and annually thereafter. Routine FDG-PET/CT surveillance is not recommended; FDG-PET/CT should be reserved for suspected recurrence or clarification of equivocal conventional imaging. Annual chest CT may be continued beyond 5 years for detection of second primary lung cancers [Class I].

Postoperative surveillance after curative-intent resection should be based primarily on chest CT. Structured follow-up is important because the risk of recurrence is highest during the first few years after surgery, while long-term survivors remain at risk of developing second primary lung cancers. The American Society of Clinical Oncology (ASCO) guideline recommends surveillance imaging every 6 months during the first 2 years and annually thereafter, identifies chest CT as the preferred modality for routine follow-up, and states that FDG-PET/CT should not be used as a routine surveillance tool (58). The 2025 ESMO guideline supports a CT-based follow-up strategy after curative-intent treatment, with follow-up intensity individualized according to recurrence risk, suitability for salvage treatment, and local practice (6). NCCN guidance is also generally aligned with CT-based surveillance and reserves FDG-PET/CT for suspected recurrence or clarification of equivocal conventional imaging rather than routine surveillance (26).

Accordingly, the expert panel adopted a CT-based surveillance strategy, with imaging approximately every 6 months during the first 2 years and annually thereafter. During the first 2 years, surveillance is primarily directed toward detection of disease recurrence, whereas longer-term annual CT is intended to support detection of second primary lung cancers (58). Annual chest CT may therefore be continued beyond 5 years in appropriate long-term survivors rather than being routinely discontinued at a fixed 5-year time point. Follow-up should be coordinated by clinicians experienced in lung cancer care.

Statement 13: stereotactic body radiotherapy (SBRT) should be offered as a curative-intent treatment for medically inoperable patients with node-negative early-stage NSCLC [Class I].

SBRT is an established curative-intent treatment for medically inoperable early-stage NSCLC and is recognized in major expert guidance as the standard local treatment in that setting (59). Modern SBRT series have demonstrated durable local control with acceptable toxicity in medically inoperable patients. In a 2023 multicentre study of 145 medically inoperable patients with early-stage NSCLC treated with SBRT, the 3- and 5-year overall survival rates were 78.1% and 70.1%, respectively. Local recurrence was 5.1% at 3 years and 9.6% at 5 years, and only 3.4% of patients experienced grade 3 treatment-related adverse events, with no grade 4 or 5 toxicity (60). These findings support SBRT as a standard curative-intent treatment for medically inoperable patients.

Statement 14: in medically operable patients with node-negative early-stage NSCLC who decline surgery after appropriate counselling, SBRT may be considered following multidisciplinary discussion [Class IIb].

For medically operable patients, surgery remains the preferred treatment, and SBRT should not be regarded as a routine substitute for surgical resection. However, in patients who decline surgery after adequate counselling, SBRT may be considered following multidisciplinary discussion of the relative benefits, risks, and uncertainties of surgical and nonsurgical treatment (59,61). Prospective comparative evidence is available from the pooled analysis of the prematurely closed STARS and ROSEL randomised trials. Among 58 operable patients with clinical T1–2aN0M0 NSCLC, the estimated 3-year overall survival was 95% with SBRT and 79% with surgery, with a hazard ratio of 0.14 [95% confidence interval (CI): 0.017–1.190; log-rank P=0.037] (62). Estimated 3-year recurrence-free survival was 86% with SBRT and 80% with surgery. Treatment-related toxicity also favoured SBRT: no patient in the SBRT group had grade 4 toxicity or treatment-related death, whereas the surgical group had one postoperative death and 44% grade 3–4 treatment-related adverse events. However, early trial closure and the very small sample size mean that these findings should be interpreted as hypothesis-generating rather than definitive evidence that SBRT is equivalent or superior to surgery in medically operable patients (62).

Larger comparative datasets also support a selective approach. In an updated meta-analysis including 29,511 patients, surgery was associated with better overall survival and cancer-specific survival overall, whereas local control was similar between surgery and SBRT (63). Accordingly, SBRT in medically operable patients who decline surgery should remain an individualized treatment option after appropriate counselling and multidisciplinary review rather than a routine alternative to surgical resection.

Statement 15: conventionally fractionated radical radiotherapy is an appropriate alternative in patients with early-stage NSCLC who are not candidates for SBRT [Class IIb].

SBRT remains the preferred radiotherapy technique for medically inoperable, node-negative early-stage NSCLC when it can be delivered safely and with adequate technical quality (6,64). However, current guidance recognizes that, in medically inoperable patients with larger tumours or less favourable anatomy, radical radiotherapy using more conventional or accelerated schedules remains an acceptable alternative (6).

Historical evidence for conventional radical radiotherapy in early-stage NSCLC shows that outcomes are modest but clinically meaningful, and clearly preferable to no curative-intent local treatment. In the systematic review by Rowell and Williams, which included one randomised trial and 26 non-randomised studies, overall survival after radical radiotherapy ranged from 22% to 72% at 2 years, from 17% to 55% at 3 years, and from 0% to 42% at 5 years, while local failure rates ranged from 6% to 70% (65). In the review by Qiao and colleagues, median survival across retrospective series ranged from 18 to 33 months, and mean overall survival at 3 and 5 years was 34% and 21%, respectively; local recurrence was the most common pattern of failure, with a median rate of 40% (66). These data support the view that conventionally fractionated radical radiotherapy can provide durable control in a subset of patients, although outcomes are generally inferior to modern SBRT. Evidence for altered conventional radical schedules also supports maintaining radiotherapy as a curative-intent option when SBRT is unsuitable. In the randomised CHART trial, continuous hyperfractionated accelerated radiotherapy improved survival compared with 60 Gy in 30 fractions, with 2-year overall survival of about 29% versus 20% (67). Although the CHART population included more than just early-stage disease, the trial supports the broader principle that definitive non-SBRT radiotherapy schedules can still achieve meaningful long-term benefit in selected patients who cannot undergo surgery or SBRT (67).

Part 3: consensus on neoadjuvant and perioperative therapy

Statement 16: technical resectability and medical operability should be established before neoadjuvant treatment is initiated. Neoadjuvant therapy should not be used routinely as a strategy to convert technically unresectable NSCLC into resectable disease [Class I].

Existing evidence supports perioperative treatment in appropriately selected resectable NSCLC, but does not support neoadjuvant therapy as a routine surgical conversion strategy. Contemporary phase III studies of neoadjuvant or perioperative immunotherapy-based treatment enrolled patients who were considered resectable at baseline according to prespecified trial eligibility criteria (11-14). A treatment pathway based on neoadjuvant therapy should therefore begin with confirmation that the tumour is technically resectable, with an R0 resection considered achievable, and that the patient is medically operable. This point is particularly important in patients with bulky or invasive N2 disease, N3 disease, or other patterns of locally advanced disease in which definitive nonsurgical treatment may be more appropriate than a surgery-based strategy (41,42). Expert discussion emphasized the importance of early multidisciplinary evaluation before neoadjuvant therapy is initiated, particularly in borderline or locally advanced cases. A cautious formulation is therefore appropriate: perioperative therapy may be incorporated into the management of resectable disease, but should not be used routinely as a strategy to convert technically unresectable NSCLC into resectable disease.

Statement 17: neoadjuvant or perioperative immunotherapy combined with platinum-based chemotherapy should be considered as a preferred treatment choice for medically operable patients who have been selected and discussed carefully in the MDT to confirm that they have technically resectable stage IIIA or selected stage IIIB NSCLC and who meet the clinicopathologic eligibility criteria and TNM staging definitions used in the relevant pivotal trial, together with applicable regulatory criteria. Patients must not have N3 disease, EGFR mutations, ALK rearrangement, or contraindications to immunotherapy; in general, this recommendation applies regardless of PD-L1 expression [Class I].

This recommendation represents one of the strongest areas of consensus and is supported by consistent phase III evidence in resectable NSCLC. In AEGEAN, perioperative durvalumab plus platinum-based chemotherapy improved event-free survival compared with chemotherapy alone [hazard ratio (HR) 0.68] and increased the pathological complete response rate from 4.3% to 17.2% (12). KEYNOTE-671 and CheckMate 77T similarly demonstrated event-free survival benefits with perioperative pembrolizumab and nivolumab, respectively, with hazard ratios of 0.58 in both trials (13,14). CheckMate 816 also showed improved event-free survival with neoadjuvant nivolumab plus chemotherapy, with an HR of 0.63 in the overall population and 0.54 in the stage IIIA subgroup (11). More mature evidence has further demonstrated significant overall survival benefits with neoadjuvant nivolumab plus chemotherapy in CheckMate 816 (HR 0.72) and perioperative pembrolizumab in KEYNOTE-671 (HR 0.72) (68,69). The 2024 IASLC consensus also supports a preference for neoadjuvant chemoimmunotherapy in medically operable patients with resectable stage III NSCLC (70). Taken together, the consistent phase III evidence, mature overall survival data, and international expert consensus support retaining a preference designation for this carefully selected stage III population.

Accordingly, this recommendation excludes patients with N3 disease. Under the AJCC/UICC TNM 9th edition, N2b denotes involvement of multiple ipsilateral mediastinal and/or subcarinal nodal stations (8,25). N2b disease should not be regarded as automatically resectable; however, selected patients with non-bulky, non-invasive N2b disease may remain candidates for a surgery-based perioperative strategy when an experienced thoracic surgeon within the MDT considers an R0 resection reasonably achievable and the patient otherwise meets the relevant trial-defined and regulatory eligibility criteria (41-43). By contrast, bulky or invasive N2 disease should generally be considered unresectable (43). Biomarker testing is required to exclude EGFR mutations and ALK rearrangements.

Although eligibility for perioperative chemoimmunotherapy is not restricted by PD-L1 expression, the magnitude of benefit may vary according to PD-L1 level. In KEYNOTE-671 and AEGEAN, event-free survival benefit was observed across PD-L1 subgroups, including patients with PD-L1 expression <1%, but was generally greater at higher PD-L1 expression levels (12,13). Current international guidelines support perioperative immunotherapy without requiring PD-L1 expression as an absolute eligibility criterion (6,26). PD-L1 expression should therefore not be used as an absolute eligibility criterion, but may inform treatment prioritization when cost, reimbursement, or access are important considerations.

Statement 18: neoadjuvant or perioperative immunotherapy combined with platinum-based chemotherapy should be considered for medically operable patients with technically resectable stage II NSCLC who meet the clinicopathologic eligibility criteria and TNM staging definitions used in the relevant pivotal trial, together with applicable regulatory criteria. Patients should not have EGFR mutations or ALK rearrangements or contraindications to immunotherapy; PD-L1 expression is not an absolute eligibility requirement [Class IIa].

Evidence for neoadjuvant or perioperative immunotherapy in resectable stage II NSCLC is evolving and is less definitive than that for stage III disease, primarily because stage II subgroup sample sizes in pivotal trials were smaller. Nevertheless, subgroup analyses generally favoured chemoimmunotherapy. In CheckMate 816, which used AJCC/UICC seventh-edition staging, the HR for event-free survival in the stage IB–II subgroup was 0.87 (95% CI: 0.48–1.56) (11). In the stage II subgroups of AEGEAN, KEYNOTE-671, and CheckMate 77T, which used eighth-edition staging, the corresponding HRs were 0.76 (95% CI: 0.43–1.34), 0.65 (95% CI: 0.42–1.01), and 0.81 (95% CI: 0.46–1.43), respectively (12-14). A systematic review and meta-analysis further showed a significant 2-year event-free survival benefit with neoadjuvant chemoimmunotherapy in patients with stage IB–II disease (HR 0.75; 95% CI: 0.57–0.97) (30).

The expert panel considered neoadjuvant or perioperative immunotherapy combined with platinum-based chemotherapy a reasonable option for patients with technically resectable stage II NSCLC who meet the relevant trial- and regulatory-defined eligibility criteria and do not have EGFR mutations or ALK rearrangements or contraindications to immunotherapy. The potential advantages of this approach include earlier systemic disease control, possible treatment of micrometastatic disease before surgery, tumour downstaging, and the opportunity to assess pathologic treatment response, as supported by phase III perioperative or neoadjuvant trials, meta-analytic evidence, and standardized post-neoadjuvant pathology assessment frameworks (11-14,27,30).

Statement 19: neoadjuvant-only and perioperative immunotherapy should be considered distinct treatment strategies in patients with resectable NSCLC. Durvalumab, pembrolizumab, and nivolumab are acceptable immune checkpoint inhibitor options when used according to the corresponding treatment strategy, with selection based on local regulatory approval, availability, reimbursement policy, affordability, institutional experience, and patient preference [Class I].

Separate phase III trials have established distinct neoadjuvant-only and perioperative immunotherapy strategies for resectable NSCLC. CheckMate 816 evaluated neoadjuvant nivolumab plus chemotherapy followed by surgery without mandated postoperative nivolumab, whereas AEGEAN, KEYNOTE-671, and CheckMate 77T evaluated perioperative strategies incorporating both neoadjuvant chemoimmunotherapy and protocol-defined postoperative durvalumab, pembrolizumab, and nivolumab, respectively (11-14). These regimens differ in eligibility criteria, chemotherapy backbones, numbers of treatment cycles, and postoperative components and should therefore not be regarded as interchangeable.

No direct comparative evidence has established the superiority of one immune checkpoint inhibitor strategy over another. Treatment selection should therefore follow the corresponding regimen and consider local regulatory approval, availability, reimbursement, affordability, institutional experience, and patient preference. The distinct trial-defined neoadjuvant and perioperative regimens are summarized separately in Table 5.

Statement 20: contrast-enhanced chest CT should be performed in all patients after neoadjuvant immunotherapy plus chemotherapy to reassess resectability [Class I].

Radiological restaging via contrast-enhanced chest CT is the established standard for evaluating tumour response following neoadjuvant therapy. Methodologically, it was a mandatory preoperative requirement across all pivotal phase III perioperative trials to confirm surgical eligibility (11,12). Post-treatment imaging provides updated anatomical assessment, helps reassess the likelihood of complete resection, and may identify treatment-related hilar or mediastinal fibrotic changes that can increase operative difficulty (71,72). Contrast-enhanced chest CT is more broadly available, more reproducible, and easier to integrate into surgical workflow than more complex repeat staging strategies. As a result, expert discussion appropriately supported post-neoadjuvant chest CT as a minimum requirement before surgery, particularly in patients with borderline resectability, mediastinal nodal disease, or uncertainty regarding the likelihood of achieving R0 resection (73).

Statement 21: routine repeat brain imaging with CT or MRI before surgery is not required in asymptomatic patients after neoadjuvant immunochemotherapy. Repeat brain MRI should, however, be considered if new neurologic symptoms develop, surgery is substantially delayed, aggressive clinical behavior raises concern for interval progression, or other clinical concerns suggest possible intracranial disease [Class III].

Unlike contrast-enhanced chest CT, which is mandatory for restaging the primary tumour bed, routine repeat brain imaging immediately before surgery is not indicated for asymptomatic patients. This recommendation aligns with the protocols of major pivotal Phase III perioperative trials, which did not mandate repeat preoperative neuroimaging for patients lacking new neurological deficits (11-14). This distinction is important because the role of chest CT after neoadjuvant therapy is to reassess the primary tumour, nodal disease, and the likelihood of complete resection, whereas the value of repeating brain MRI over a short neoadjuvant interval is less well supported. Although prospective data specifically quantifying intracranial progression during the neoadjuvant window remain limited, the interval between initiation of neoadjuvant therapy and surgery is usually short, and clinically significant isolated brain progression in a patient with negative baseline CNS staging and no new neurologic symptoms is expected to be uncommon. The interpretation is also consistent with broader oncologic imaging guidance, which does not support routine brain MRI surveillance in asymptomatic patients after curative-intent treatment and instead reserves CNS imaging for patients with symptoms or specific clinical suspicion (58,74). New neurologic symptoms should prompt consideration of repeat brain MRI, given the strong association between neurologic symptoms and intracranial metastases in NSCLC. In one clinical cohort, brain metastases were identified in 28 of 43 patients (67%) presenting with central neurologic symptoms (75). Repeat brain MRI may also be considered when the interval to surgery is substantially prolonged or when aggressive clinical behavior or other findings raise concern for interval progression, consistent with recommendations for timely preoperative staging and imaging when recurrence or progression is clinically suspected (74,76). From a practical perspective, avoiding routine repeat brain imaging in asymptomatic patients is also reasonable in the Vietnamese setting. A reflex policy of repeating brain MRI or CT in every patient before surgery may increase cost, consume imaging capacity, and prolong the interval to planned resection without clear evidence of clinical benefit.

Statement 22: cases in which technical resectability or medical operability remains uncertain after neoadjuvant therapy should undergo repeat multidisciplinary review before proceeding to surgery [Class I].

Cases with persistent uncertainty after neoadjuvant therapy remain among the most challenging decision points in resectable NSCLC. In the international EORTC survey of 558 multidisciplinary experts, no consensus was reached for 11 of 37 stage III TNM subsets, representing 30% of the scenarios assessed (41). Areas of disagreement included multistation N2 disease, larger tumours with single-station N2 involvement, and selected invasive T4 presentations (41). The subsequent multi-societal Delphi initiative concluded that decisions regarding resectability in stage III NSCLC should be made by experienced thoracic surgeons within the framework of a MDT (43). These findings provide a strong academic basis for repeat MDT review when uncertainty persists after neoadjuvant treatment.

Uncertainty after neoadjuvant therapy may arise from both tumour anatomy and patient physiology. Surgical reviews have described hilar and mediastinal fibrosis, vascular fragility, adhesions, and more difficult dissection after neoadjuvant immunotherapy, all of which may alter operative feasibility, increase technical complexity, and raise the likelihood of conversion to thoracotomy (77). In a cohort of stage III patients treated with neoadjuvant therapy and surgery, 23.9% had no clinical N2 downstaging at reassessment, and in such cases surgery was recommended only after renewed multidisciplinary discussion (78). In the OBSERVE IIIA to B study, none of the 27 tumour board decisions across 6 stage III N2 cases was completely unanimous, and in 3 cases the proportions favouring medical and surgical strategies were nearly balanced (79). In Vietnam, where access to advanced staging tools and specialist thoracic surgical review may vary across centres (80), repeat MDT discussion provides the safest framework for judging whether surgery remains appropriate.

Statement 23: the preferred interval between completion of neoadjuvant immunotherapy plus chemotherapy and surgery is approximately four to six weeks, provided treatment-related toxicities have adequately resolved and repeat assessment confirms surgical readiness, continued technical resectability and medical operability [Class I].

Regarding timing, both CheckMate 816 and CheckMate 77T scheduled surgery within 6 weeks after completion of neoadjuvant treatment (11,14), whereas AEGEAN specified surgery within 40 days, with a median observed interval of 34 days (12,81). KEYNOTE-671 used a broader protocol-defined window, with surgery required no later than 20 weeks after the first neoadjuvant dose; subsequent analyses defined surgical delay as more than 20 weeks in patients completing four cycles or more than 8 weeks after the last dose in those receiving fewer than four cycles (13,73). Despite these protocol differences, the pivotal studies broadly support a practical surgical interval of approximately 4–6 weeks.

Observational evidence also supports avoiding unnecessary delay. In a National Cancer Database (NCDB) analysis of patients treated with neoadjuvant chemoradiotherapy, surgery at 6–9 weeks and 9–12 weeks was associated with higher mortality compared with surgery within 6 weeks (HR 1.33 and 1.44, respectively) (82). Although this cohort did not receive chemoimmunotherapy, more recent data are directionally consistent: a 2026 multicentre study of neoadjuvant immunochemotherapy found that surgery at 4–6 weeks was associated with the most favourable outcomes, whereas surgery before 4 weeks was associated with a lower pCR rate and surgery after 6 weeks with worse disease-free and overall survival, particularly among patients without pCR (83). Other retrospective studies have produced somewhat variable findings regarding the optimal interval (83-85).

The panel therefore considered approximately 4–6 weeks a preferred target, provided that treatment-related toxicities have resolved and reassessment confirms surgical readiness, continued technical resectability and medical operability. This interval should not be applied rigidly, and short deviations may be reasonable to allow clinical recovery or address logistical constraints; however, unnecessary postponement should be avoided (76).

Statement 24: pathologic complete response (pCR) and major pathologic response (MPR) should be standardised and incorporated into routine surgical pathology reporting after neoadjuvant therapy [Class IIa].

The 2020 recommendations of the IASLC established the principal framework for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy (27). Within this framework, pCR is defined as absence of viable tumour cells in the resected primary tumour and sampled regional lymph nodes, whereas MPR is defined as ≤10% residual viable tumour in the treated primary tumour bed, with nodal findings reported separately (27,86). Routine pathology reports should therefore include pathologic treatment response in addition to histologic diagnosis and post-treatment pathologic TNM stage (86,87).

The clinical relevance of standardized response assessment is reinforced by its incorporation into contemporary phase III trials. In KEYNOTE-671, MPR occurred in 30.2% versus 11.0% and pCR in 18.1% versus 4.0% of patients receiving perioperative pembrolizumab and placebo, respectively (13). In CheckMate 77T, pCR occurred in 25.3% versus 4.7% and MPR in 35.4% versus 12.1% with perioperative nivolumab and control treatment, respectively (14). pCR and MPR were also prespecified efficacy endpoints in CheckMate 816 and AEGEAN (11,12). These data underscore the increasing importance of standardized pathologic response assessment in the interpretation of modern perioperative treatment.

Standardization is particularly important because definitions have not been fully uniform across trials. CheckMate 816, KEYNOTE-671, and CheckMate 77T evaluated MPR using both the primary tumour and sampled lymph nodes, whereas AEGEAN defined MPR in relation to the primary tumour (11-14). The IASLC framework emphasizes MPR in the treated primary tumour bed with separate reporting of nodal response (27,86,88), providing a consistent basis for routine reporting.

Because the evidence supporting standardized pCR or MPR reporting derives primarily from methodological recommendations, reporting standards, and treatment trials rather than comparative studies evaluating the reporting strategy itself, the panel considered Class IIa appropriate. In Vietnam, practical implementation may include synoptic reporting templates, structured grossing protocols, targeted pathologist training, and second review for difficult cases where feasible (27,80,89).

Statement 25: when a patient begins a trial-validated perioperative regimen, the planned postoperative immunotherapy should generally be administered if postoperative recovery and treatment-related toxicities permit. Postoperative immunotherapy should not be added routinely after a neoadjuvant-only regimen, and the incremental benefit of postoperative immunotherapy according to pCR or MPR remains uncertain [Class IIa].

Contemporary phase III trials in resectable NSCLC evaluated distinct neoadjuvant-only and perioperative treatment strategies. CheckMate 816 evaluated neoadjuvant nivolumab plus chemotherapy followed by surgery without mandated postoperative nivolumab, whereas AEGEAN, KEYNOTE-671, and CheckMate 77T incorporated both preoperative immunochemotherapy and protocol-defined postoperative checkpoint inhibition (11-14). Accordingly, when a patient begins a trial-validated perioperative regimen, the planned postoperative component should generally be administered if postoperative recovery and treatment-related toxicities permit. However, no prospective randomized trial has directly isolated the incremental benefit of postoperative immunotherapy over neoadjuvant chemoimmunotherapy alone. A patient-level indirect comparison between CheckMate 77T and CheckMate 816 suggested improved event-free survival with the perioperative approach, particularly among patients who did not achieve a pCR and those with PD-L1-negative tumours (90). However, this indirect comparison cannot establish the specific contribution of the postoperative immunotherapy component, and the incremental benefit according to pCR or MPR remains uncertain.

Given these uncertainties, the consensus panel emphasized that real-world application requires pragmatic flexibility, particularly in the Vietnamese healthcare context. Administration of the planned postoperative component of a perioperative regimen may not be appropriate or feasible in every patient. Such decisions should take into account postoperative recovery, unresolved toxicities, pathologic response, drug access, and financial considerations, while recognizing that pCR or MPR has not been established as a predictor of incremental benefit from postoperative immunotherapy; decisions should ideally be made through multidisciplinary discussion. Postoperative immunotherapy should not be routinely added after a neoadjuvant-only regimen in which it was not part of the studied treatment strategy.

Statement 26: at present, circulating tumour DNA should not be used routinely as a clinical decision-making tool in the postoperative management of resectable NSCLC [Class III].

Circulating tumour DNA (ctDNA)-based MRD assessment is scientifically promising because postoperative ctDNA positivity is associated with a higher risk of recurrence and may precede radiologic relapse (91,92). However, prognostic value does not establish clinical utility for treatment selection. Current assays remain limited by imperfect analytical sensitivity, false-negative results in low-shedding disease, assay heterogeneity, and the absence of prospective validation showing that ctDNA-guided treatment escalation or de-escalation improves patient outcomes (91-93).

Exploratory findings from IMpower010 further illustrate this limitation. Postoperative ctDNA-negative patients still derived disease-free survival benefit from adjuvant atezolizumab, and benefit was observed regardless of ctDNA status, indicating that a negative result cannot currently justify omission of otherwise indicated adjuvant therapy (94). Consistently, the ASCO surveillance guideline does not recommend circulating biomarkers for routine surveillance after definitive curative-intent treatment (58). Published Vietnamese studies cited in this consensus have not established a role for ctDNA-guided postoperative treatment (80,89). The expert panel supported a conservative implementation strategy: postoperative management should continue to rely on established clinicopathologic factors, histopathology, imaging surveillance, and approved adjuvant therapies rather than routine ctDNA-guided decisions.

Statement 27: patients who develop disease progression during or after neoadjuvant therapy should undergo complete restaging and repeat MDT reassessment before any decision to proceed with surgery [Class IIa].

Disease progression during or after neoadjuvant therapy is a clinically important situation in the management of resectable NSCLC. A proportion of patients who begin induction treatment will no longer remain suitable for surgery as initially planned because of interval progression, newly detected metastatic disease, treatment-related toxicity, decline in performance status, or reassessment of technical unresectability (11,73). Under such circumstances, routine progression to surgery is no longer appropriate, but immediate abandonment of curative-intent treatment may also be unjustified. Complete restaging and repeat MDT reassessment are therefore necessary before any decision to proceed with surgery, to clarify current disease status, technical resectability, medical operability, and the most appropriate next therapeutic step (42). Subsequent management may need to shift toward definitive chemoradiotherapy, systemic therapy, local treatment for limited progression, or supportive care, depending on disease extent, treatment tolerance, and patient fitness (42). The panel therefore supported repeat multidisciplinary discussion whenever progression occurs after induction treatment, so that subsequent management can be aligned with disease behavior, patient condition, and local feasibility while preserving curative intent whenever still appropriate.

Part 4: consensus on adjuvant treatment

Statement 28: in resected NSCLC, the surgical specimen should undergo not only definitive pathological classification but also biomarker assessment for EGFR mutation, ALK rearrangement, and PD-L1 expression (if not already performed on the preoperative biopsy) [Class I].

The resected specimen should be regarded as the definitive material for final histopathologic classification and completion of postoperative biomarker assessment. The 2021 WHO classification emphasizes that lung tumour diagnosis should remain morphology-based, with immunohistochemistry used in a limited and tissue-conserving manner on small biopsies; in most poorly differentiated non-small cell carcinomas, a minimal panel such as TTF-1 and p40 is generally sufficient to support adenocarcinoma-versus-squamous differentiation while preserving tissue for molecular testing (24). By contrast, the surgical specimen allows more complete morphologic subtyping, more reliable pathologic staging, and more adequate material for downstream molecular and immunohistochemical assays (24). As a consequence, surgery should not be regarded as the end of the diagnostic pathway, but rather as the point at which postoperative pathology and the molecular profile can be completed to support precision adjuvant decision-making (6).

Completion of postoperative biomarker testing is directly linked to evidence-based adjuvant treatment selection. In completely resected EGFR-mutated disease, adjuvant osimertinib improved overall survival in ADAURA (10). In ALK-positive disease, adjuvant alectinib improved disease-free survival in ALINA (15). PD-L1 expression also remains clinically relevant because IMpower010 demonstrated disease-free survival benefit with adjuvant atezolizumab after platinum-based chemotherapy in patients with resected stage II–IIIA NSCLC whose tumours expressed PD-L1 on at least 1% of tumour cells, with subsequent overall survival analyses showing the most favourable trend in PD-L1-high disease (28,95). Biomarker testing on the surgical specimen is therefore essential whenever preoperative testing was incomplete, inadequate, or unavailable. Panel experts further emphasized that PD-L1 testing should be regarded as part of standard postoperative biomarker completion rather than as an optional later step. In routine practice, especially when preoperative biopsy material is limited, the resected specimen may provide the most appropriate and reliable tissue source for definitive EGFR, ALK, and PD-L1 assessment before adjuvant treatment decisions are finalized.

Statement 29: adjuvant systemic therapy after complete resection should be guided by pathologic stage, biomarker profile, prior treatment, and relevant trial and regulatory eligibility criteria. Chemotherapy, EGFR- or ALK-targeted therapy, and immune checkpoint inhibitors should be selected and sequenced according to the evidence and indications applicable to each specific therapeutic strategy [Class I].

Adjuvant treatment in resected NSCLC is no longer defined by chemotherapy alone. Current practice requires an individualized postoperative strategy based on pathologic stage, adverse histopathologic features, biomarker profile, prior treatment, and the patient’s recovery after surgery (10,15,28,96). Platinum-based chemotherapy remains an established component of adjuvant treatment, while EGFR- or ALK-targeted therapy and immune checkpoint inhibitors have introduced additional biomarker-directed strategies for appropriately selected patients (9,10,15,28).

This recommendation defines the overall framework of adjuvant management rather than the detailed indication for each modality. Adjuvant treatment should therefore be organized according to pathologic stage, biomarker status, and treatment sequence rather than treating chemotherapy, targeted therapy, and immunotherapy as mutually exclusive alternatives. In practical terms, platinum-based chemotherapy generally precedes osimertinib in eligible patients with EGFR exon 19 deletion- or exon 21 L858R-positive disease for whom adjuvant chemotherapy is indicated, and precedes appropriately selected adjuvant immunotherapy in EGFR- and ALK-negative disease (10,29,95). ALK-positive disease treated with adjuvant alectinib represents an important exception because preceding chemotherapy is not required when this strategy is selected (15). In stage IB disease, postoperative treatment should be individualized according to tumour size, pathologic risk factors, TNM edition, biomarker status, and the eligibility criteria of the specific adjuvant therapy under consideration. Detailed therapy-specific indications and sequencing are addressed in the subsequent statements. In Vietnam, where actionable EGFR alterations are common in resected non-squamous NSCLC, completion of postoperative biomarker testing is particularly important to ensure that adjuvant treatment is matched appropriately to tumour biology (16).

Statement 30: patients with completely resected stage II–IIIA NSCLC who are eligible for adjuvant chemotherapy should receive cisplatin-based adjuvant chemotherapy. In selected high-risk stage IB disease, cisplatin-based adjuvant chemotherapy may be considered. The use and sequencing of chemotherapy with subsequent biomarker-directed adjuvant therapy should follow the indication applicable to each treatment strategy [Class I].

Adjuvant chemotherapy remains an important component of postoperative treatment in completely resected NSCLC and should be considered according to pathologic stage and the planned treatment sequence rather than only in the absence of targeted or immune-based treatment options (6,9). The central evidence base remains the Lung Adjuvant Cisplatin Evaluation (LACE) pooled analysis of 4,584 patients, which showed that cisplatin-based adjuvant chemotherapy improved overall survival compared with observation, with a hazard ratio of 0.89 and an absolute 5-year survival benefit of 5.4%; disease-free survival was also improved, with a hazard ratio of 0.84 (96). The survival effect varied by pathologic stage, with possible detriment in stage IA disease, no clear overall survival benefit in stage IB overall, and the most consistent benefit in stage II and stage III disease (96). Given this, platinum-based adjuvant chemotherapy is most strongly supported in completely resected stage II–IIIA disease, while selected stage IB cases should be considered individually according to tumour size and adverse pathologic features rather than treated automatically (6,96).

Cisplatin should generally be preferred over carboplatin when medically feasible. Mature results from CALGB 9633 did not show a statistically significant overall survival benefit for adjuvant carboplatin-paclitaxel across the entire stage IB population, although an exploratory subgroup analysis suggested benefit in tumours measuring at least 4 cm (97). Carboplatin-based adjuvant therapy should not be regarded as an equivalent routine substitute for cisplatin-based chemotherapy, but may still be considered in selected patients who are otherwise appropriate for adjuvant treatment but cannot safely receive cisplatin (6,97). Eligibility for chemotherapy should also take into account postoperative recovery, performance status, organ function, comorbidities, and treatment tolerance.

Statement 31: patients with completely resected EGFR exon 19 deletion- or exon 21 L858R-positive NSCLC who meet the ADAURA-defined eligibility criteria (stage IB–IIIA according to the AJCC/UICC seventh edition) and applicable regulatory criteria should receive adjuvant osimertinib 80 mg once daily for 3 years. In patients with stage II–IIIA disease who are eligible for cisplatin-based adjuvant chemotherapy, chemotherapy should generally be administered before osimertinib. In stage IB disease, or when cisplatin is contraindicated, the decision regarding adjuvant chemotherapy should be individualized [Class I].

The ADAURA trial enrolled patients with completely resected stage IB–IIIA NSCLC according to the AJCC/UICC seventh edition whose tumours harboured an EGFR exon 19 deletion or exon 21 L858R mutation (98). Patients were randomised to receive osimertinib 80 mg once daily or placebo for up to 3 years after surgery. Updated analysis showed a substantial disease-free survival benefit, with median disease-free survival of 65.8 months with osimertinib versus 28.1 months with placebo and a hazard ratio of 0.27 in the overall stage IB–IIIA population; benefit was observed across stage IB, II, and IIIA subgroups (99). Osimertinib also reduced locoregional, distant, and CNS recurrence (98,99). These findings support adjuvant osimertinib specifically for the EGFR exon 19 deletion- and exon 21 L858R-positive population studied in ADAURA rather than broadly for all EGFR alterations.

Cisplatin-based adjuvant chemotherapy should remain an important component of postoperative treatment for eligible patients with stage II–IIIA disease and should generally precede osimertinib. ADAURA did not evaluate osimertinib as a replacement for otherwise indicated adjuvant chemotherapy; chemotherapy was permitted before randomisation when clinically indicated, and approximately 60% of patients received prior chemotherapy, with the benefit of osimertinib maintained regardless of prior chemotherapy use (100). This treatment sequence is also consistent with the established survival benefit of cisplatin-based adjuvant chemotherapy in resected stage II–III disease (96). In contrast, the chemotherapy decision should be individualized in stage IB disease or when cisplatin is contraindicated (96,100).

Statement 32: patients with completely resected ALK-positive NSCLC who meet the trial-defined stage eligibility criteria (stage IB with tumours measuring at least 4 cm, stage II, or stage IIIA according to the AJCC/UICC seventh edition) and applicable regulatory criteria should receive adjuvant alectinib 600 mg twice daily for 2 years. Platinum-based adjuvant chemotherapy is not required when alectinib is selected as the postoperative systemic treatment [Class I].

ALK rearrangement is an important actionable driver alteration in NSCLC and is detected in a small but clinically meaningful proportion of resected cases. These tumours occur more commonly in younger patients and never-smokers or light smokers, and have a recognised propensity for CNS relapse (15,101). For that reason, identification of ALK status after complete resection now has direct implications for postoperative treatment selection rather than serving merely as descriptive molecular information.

The phase III ALINA trial enrolled patients with completely resected ALK-positive NSCLC meeting trial-defined stage criteria of stage IB with tumours measuring at least 4 cm, stage II, or stage IIIA according to the AJCC/UICC seventh edition (15). Eligible patients were randomised to receive alectinib 600 mg twice daily for 24 months or platinum-based chemotherapy. Alectinib significantly prolonged disease-free survival compared with chemotherapy. In the stage II–IIIA population, the 2-year disease-free survival rate was 93.8% with alectinib and 63.0% with chemotherapy, with a hazard ratio for recurrence or death of 0.24. In the overall stage IB–IIIA population, the corresponding 2-year disease-free survival rates were 93.6% and 63.7%, respectively, again with a hazard ratio of 0.24. Alectinib was also associated with a clinically meaningful improvement in CNS disease-free survival, with a hazard ratio of 0.22 (15). Overall survival data were immature at the time of publication, but the magnitude and consistency of the disease-free survival benefit strongly support adjuvant alectinib as a major postoperative advance in ALK-positive resected NSCLC.

On the basis of ALINA, the US Food and Drug Administration approved alectinib as adjuvant treatment following tumour resection in adults with ALK-positive NSCLC with tumours ≥4 cm or node-positive disease, at a dose of 600 mg orally twice daily for 2 years or until recurrence or unacceptable toxicity (102). Given that ALINA demonstrated clear superiority over platinum-based chemotherapy, adjuvant alectinib should be regarded as a preferred postoperative systemic option in eligible ALK-positive patients, rather than as a tentative or exploratory strategy (15). Furthermore, a Vietnamese molecular profiling study reported ALK alterations in 6.6% of NSCLC cases, indicating that although ALK-positive disease is less common than EGFR-mutated disease, it remains a clinically important subgroup in routine practice (101). Based on these results, the panel considered completion of ALK testing on diagnostic biopsy or resected tumour tissue essential so that eligible patients with completely resected ALK-positive NSCLC can be identified promptly and offered adjuvant alectinib when accessible.

Statement 33: in patients with completely resected EGFR-negative and ALK-negative NSCLC, adjuvant atezolizumab or pembrolizumab may be considered in appropriately selected patients according to the distinct trial and regulatory eligibility criteria applicable to each agent. Patient selection and treatment should account for the relevant TNM edition, prior adjuvant platinum-based chemotherapy, PD-L1 requirements where applicable, treatment duration, and current regulatory indications [Class IIa].

Adjuvant immunotherapy has an established but agent-specific role in completely resected EGFR-negative and ALK-negative NSCLC. The phase III IMpower010 trial evaluated atezolizumab after complete resection and 1 to 4 cycles of cisplatin-based adjuvant chemotherapy in patients with stage IB tumours measuring at least 4 cm through stage IIIA disease according to the AJCC/UICC seventh edition (28). The prespecified primary efficacy population included patients with stage II–IIIA disease whose tumours expressed PD-L1 on at least 1% of tumour cells, assessed using the VENTANA PD-L1 SP263 assay. Atezolizumab improved disease-free survival in this population, with a hazard ratio of 0.66, while a smaller but significant benefit was also observed in the overall stage II–IIIA population, with a hazard ratio of 0.79 (28). Subsequent overall survival analysis remained immature, although the most favourable trend was observed in patients with higher PD-L1 expression (95). Atezolizumab was administered every 3 weeks for 16 cycles, corresponding to approximately 1 year. In Vietnam, atezolizumab is approved for adjuvant treatment after complete resection and platinum-based chemotherapy in adults with stage II–IIIA NSCLC whose tumours express PD-L1 on at least 1% of tumour cells, and its use should follow the locally approved prescribing information (103).

The phase III PEARLS/KEYNOTE-091 trial evaluated pembrolizumab after complete resection in patients with stage IB tumours measuring at least 4 cm, stage II, or stage IIIA NSCLC according to the AJCC seventh edition (29). Adjuvant chemotherapy was considered for stage IB disease and strongly recommended for stage II–IIIA disease, although it was not mandatory for trial enrolment; 86% of patients ultimately received adjuvant chemotherapy. Pembrolizumab was administered at 200 mg every 3 weeks for up to 18 cycles, corresponding to approximately 1 year, and improved disease-free survival in the overall study population, with a hazard ratio of 0.76 (29). PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx assay, but the co-primary endpoint in the PD-L1 tumour proportion score of 50% or higher population was not met. Thus, unlike atezolizumab, pembrolizumab does not require a PD-L1 expression threshold for patient selection. In Vietnam, pembrolizumab is approved for adjuvant treatment after complete resection and platinum-based chemotherapy in adults with stage IB disease with tumours measuring at least 4 cm, stage II, or stage IIIA disease, irrespective of PD-L1 expression, and its use should follow the locally approved prescribing information (104).

These differences support an agent-specific approach to adjuvant immunotherapy rather than applying a single eligibility framework to both agents. Table 6 summarizes the practical stage- and biomarker-based perioperative and adjuvant treatment pathways, including applicable eligibility criteria and TNM editions, required biomarkers, treatment sequence, regimen duration, recommendation class, consensus agreement, agent- and setting-specific regulatory status in Vietnam, and major access considerations.

Statement 34: postoperative radiotherapy (PORT) is not routinely recommended after complete (R0) resection. Selected high-risk situations may be considered individually through multidisciplinary discussion [Class I].

The routine use of PORT after R0 resection is not supported by the best available evidence. In the individual-patient-data meta-analysis of 2,128 patients from nine randomised trials, PORT increased the risk of death by 21% (HR 1.21; 95% CI: 1.08–1.34), corresponding to an absolute 7% reduction in 2-year overall survival from 55% to 48% (105). The updated Cochrane review, based on 11 trials and 2,343 patients, confirmed a detrimental effect on survival (HR 1.18; 95% CI: 1.07–1.31), reducing 2-year overall survival from 58% to 53% (106).

In the modern radiotherapy era, phase III randomised data in resected pN2 disease still have not shown a survival advantage for routine PORT. In the Lung ART trial, 3-year disease-free survival was 47.1% with PORT versus 43.8% with observation, whereas 3-year overall survival was 66.5% versus 68.5%, respectively, and cardiopulmonary toxicity was higher in the PORT arm (107). In PORT-C, PORT did not improve disease-free survival in the modified intention-to-treat analysis (HR 0.90; 95% CI: 0.70–1.12; P=0.39) (108). Long-term PORT-C follow-up likewise showed no overall survival advantage, with 5-year overall survival of 64.7% in the PORT group and 70.4% in the observation group (P=0.20), although locoregional recurrence-only events were reduced and cardiopulmonary deaths were more frequent with PORT (109). The expert panel considered that PORT should not be routinely used after complete R0 resection, including in patients with pN2 disease; however, selected high-risk situations may warrant individualized MDT review.

Statement 35: PORT, commonly 60 Gy in 30 fractions, may be considered after microscopically incomplete (R1) resection when re-resection to achieve negative margins is not feasible or appropriate, following multidisciplinary discussion, and the sequencing of PORT with systemic therapy should be individualized. Macroscopically incomplete (R2) resection should be managed separately through multidisciplinary evaluation [Class IIa].

After microscopically incomplete (R1) resection, PORT is primarily intended to improve locoregional control in the presence of microscopic residual disease. When clinically and technically feasible, re-resection to achieve negative margins should be considered before PORT. If re-resection is not feasible or appropriate, PORT may be considered following multidisciplinary discussion, although the supporting evidence remains largely retrospective. Postoperative doses for involved microscopic margins are generally in the range of 54–60 Gy, consistent with the commonly used regimen of 60 Gy in 30 fractions (110-112). In one institutional study of incompletely resected NSCLC, the median PORT dose was 59.4 Gy, the 3-year locoregional relapse-free survival was 82.1%, and the 3-year overall survival was 58.2% (113). In another series of 78 patients with R1 disease treated with PORT, the median dose was 60 Gy, and doses >54 Gy were associated with significantly better overall survival and local control outcomes (114). Meanwhile, previous studies support the biological and clinical plausibility of PORT in the R1 setting, even though they do not provide randomised proof (113,114). By contrast, macroscopically incomplete (R2) resection represents gross residual disease and should be considered separately from R1 disease. When radiotherapy is indicated in this setting, doses of approximately 60–66 Gy have commonly been used, with treatment individualized according to the extent of residual disease, normal-tissue constraints, and integration with systemic therapy (115).

Population-based evidence is supportive but not fully consistent, which is why a Class IIa recommendation is more appropriate than a stronger statement. In an NCDB analysis of 3,395 patients with stage II–III margin-positive NSCLC treated after lobectomy or pneumonectomy, PORT delivered at 50–74 Gy was associated with improved overall survival on multivariable analysis (HR 0.80, 95% CI: 0.70–0.92) (116). However, a broader NCDB analysis stratified by stage and adjuvant modality found no survival benefit with radiation alone in any margin-positive stage group; instead, patients with IIA(N1)/IIB and IIIA disease had better survival with chemotherapy or chemoradiation, not PORT alone (117). The inconsistent findings across prior studies argue against the routine or indiscriminate use of PORT monotherapy and support formal multidisciplinary discussion to optimize patient selection and coordination with systemic treatment.

Additional data also support individualizing the sequence of PORT and systemic therapy rather than mandating a single fixed order. In a study of pIIIA-N2 patients with positive margins, PORT alone did not significantly improve overall survival in the full cohort, but among R1 patients, PORT plus chemotherapy was associated with substantially longer median overall survival than surgery alone (52.4 vs. 17.2 months; P=0.027) (115). In that same series, concurrent and sequential chemoradiation produced similar overall survival, reinforcing the principle that treatment order should be tailored according to postoperative recovery, nodal burden, systemic relapse risk, comorbidity, and expected treatment tolerance (115). Consequently, after R1 resection, when re-resection to achieve negative margins is not feasible or appropriate, PORT may be considered to address residual microscopic disease, but the decision to irradiate, the dose and fields, and the sequencing relative to chemotherapy or other systemic therapy should all be individualized through MDT review rather than treated as an automatic postoperative standard.

Strengths and limitations

This study represents, to our knowledge, the first structured Vietnamese multidisciplinary expert initiative focused specifically on the diagnosis and perioperative management of resectable NSCLC. A major strength is that the consensus statements were developed through a modified Delphi-informed hybrid process that combined scoping, practice mapping, targeted evidence review, expert discussion, written feedback, recirculation, and formal statement-level voting. The process included specialists from the core disciplines involved in resectable NSCLC care, and the final consensus statements were explicitly contextualized to Vietnamese implementation realities, including variation in access to staging tools, molecular diagnostics, perioperative therapy, pathology services, and MDT infrastructure.

Several limitations should also be acknowledged. First, the process was not a classical Delphi with repeated fully anonymous statement-level rating across all sections; rather, it combined face-to-face or hybrid discussion, confidential written feedback, recirculation, and formal voting. Second, panel representation, although multidisciplinary, was not evenly distributed across specialties and geographic regions. Third, no patient or public representative was involved; therefore, the document primarily reflects professional and health-system perspectives. Fourth, several implementation-oriented recommendations required contextual interpretation of international evidence because direct evidence from Vietnamese clinical practice remains limited. Finally, the document was designed as an evidence-informed framework for current use in Vietnam and has not yet undergone formal external validation or prospective evaluation of its impact on practice or patient outcomes.

Conclusions

This document provides a multidisciplinary, evidence-informed framework for the diagnosis and management of resectable NSCLC in Vietnam, covering preoperative diagnosis and staging, biomarker evaluation, surgical principles, postoperative surveillance, neoadjuvant and perioperative therapy, and adjuvant treatment. By contextualizing contemporary international evidence within the realities of Vietnamese clinical practice, it may help improve consistency of care across institutions, support more appropriate biomarker-guided and multimodality treatment, and strengthen multidisciplinary decision-making in routine thoracic oncology practice. Given the rapid advances in thoracic oncology, including evolving perioperative treatment indications and staging systems, this consensus is planned for biennial review and will be updated as needed to reflect emerging evidence and changes in local implementation capacity.

Acknowledgments

The authors gratefully acknowledge all the experts and professional societies whose time, expertise, and commitment contributed to the development of the Vietnamese expert consensus on the diagnosis and multidisciplinary management of resectable NSCLC.

Footnote

Reporting Checklist: The authors have completed the ACCORD reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0852/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0852/prf

Funding: This work was supported by an educational grant from AstraZeneca Vietnam, which also provided medical writing support for manuscript preparation. The sponsor had no role in study design, data collection, analysis, interpretation, manuscript writing, or the decision to submit for publication.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0852/coif). All authors report the present project was supported by an educational grant from AstraZeneca Vietnam, which also provided medical writing support. 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. The consensus protocol was approved by the Institutional Review Board of Thong Nhat Hospital, Ho Chi Minh City, Vietnam (approval No. 92/2025/CN-BVTN-HĐĐĐ, dated 27 June 2025). This project involved expert consultation only and did not include patient participation or the collection of patient-level data. Participation was voluntary. All formal ratings, voting, and written feedback were handled confidentially, and the manuscript reports aggregated results only.

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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