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Overview and Recommendations
Background
- •Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers, and surgical resection remains the only potentially curative therapy for localized disease. Stage I disease achieves 5-year survival rates exceeding 70% after complete (R0) resection, making early detection and operative intervention critical.
- •Surgical eligibility is determined by clinical stage (TNM), histologic subtype, molecular profile, and patient fitness. Stage I-IIIA(N2) disease is generally resectable with curative intent, while stage IIIB(N3) and stage IV are typically treated with definitive chemoradiation or systemic therapy alone.
- •The paradigm of surgical management has shifted from upfront surgery alone to a multimodality approach. For stage II-IIIA, neoadjuvant or perioperative chemo-immunotherapy is now standard, superseding surgery-first strategies. This change is driven by trials showing improved event-free survival and pathologic complete response rates.
- •Molecular subtypes (EGFR, ALK, RET) strongly influence adjuvant therapy decisions. For resected EGFR-mutated NSCLC, adjuvant osimertinib 80 mg daily for 3 years improves 4-year disease-free survival from 29% to 70%. Similarly, adjuvant ensartinib 225 mg daily for 24 months dramatically improves outcomes in ALK-positive disease.
- •Minimally invasive approaches, video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), have become the standard for early-stage NSCLC, offering reduced pain, shorter hospital stay, and equivalent oncologic outcomes compared with open thoracotomy.
Evaluation
- •Suspect surgical candidacy in any patient with a new lung nodule or mass on imaging. Begin with a thorough history: smoking history, performance status, comorbidities (especially COPD, heart disease), and prior thoracic surgery.
- •Examine for signs of advanced disease: supraclavicular lymphadenopathy, hoarseness (recurrent laryngeal nerve), pleural effusion, or weight loss. These may indicate unresectable disease.
- •Order contrast-enhanced CT chest through the adrenal glands for initial staging. PET/CT is essential for detecting nodal and distant metastases. Brain MRI is recommended for stage II-IV disease to rule out brain metastases.
- •Perform mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and/or endoscopic ultrasound (EUS) for all patients with suspected N2/N3 disease. Combined EBUS+EUS has a diagnostic accuracy of 0.99, comparable to mediastinoscopy.
- •Assess cardiopulmonary fitness: pulmonary function tests (FEV1, DLCO), cardiac stress testing if coronary artery disease is suspected, and exercise capacity. The 8-week smoking cessation threshold is critical, it reduces postoperative pulmonary complications (OR 0.42).
- •Evaluate frailty using the Veterans Affairs Frailty Index, which strongly predicts major complications (adjusted OR 2.85). Consider formal prehabilitation (exercise, nutrition, anxiety reduction) for high-risk patients starting 4 weeks before surgery.
- •Determine resectability based on clinical stage: Stage I (T1-2aN0) is resectable; Stage II (T1-2bN1, T3N0) is resectable with neoadjuvant therapy; Stage IIIA (N2) is selectively resectable after induction therapy; Stage IIIB (N3) is unresectable.
- •Obtain molecular testing (EGFR, ALK, RET, PD-L1) on biopsy tissue. Results guide neoadjuvant treatment decisions (e.g., osimertinib for EGFR-mutated) and adjuvant therapy planning.
- •Multidisciplinary team discussion (thoracic surgery, medical oncology, radiation oncology, pulmonology, pathology) is mandatory before any treatment decision. This ensures optimal sequencing and avoids inappropriate surgery.
Management
- •For stage IA NSCLC, perform lobectomy with systematic mediastinal lymph node sampling or dissection. For ground-glass opacity (GGO)-dominant invasive adenocarcinoma ≤3 cm and consolidation-to-tumor ratio ≤0.5, systematic mediastinal lymph node dissection can be safely omitted, it does not improve survival and increases operative time and blood loss.
- •For stage IA with small peripheral tumors (≤2 cm), consider segmentectomy as an alternative to lobectomy. The pooled hazard ratio for overall survival in stage IA is 1.10 (favoring lobectomy) but not statistically significant, so sublobar resection is reasonable in selected patients.
- •For stage IB with tumors ≥4 cm, consider adjuvant platinum-based chemotherapy (e.g., cisplatin plus vinorelbine). CALGB 9633 showed a significant survival benefit for tumors ≥4 cm (HR 0.69). For stage IB <4 cm, no adjuvant therapy is indicated.
- •For stage II-IIIA, administer neoadjuvant chemo-immunotherapy (e.g., platinum doublet plus nivolumab, pembrolizumab, or tislelizumab). This is the preferred approach over upfront surgery. The RATIONALE-315 trial showed perioperative tislelizumab plus chemotherapy improved overall survival (HR 0.65) and event-free survival (HR 0.58).
- •For resected stage II-IIIA without driver mutations, give adjuvant cisplatin-based chemotherapy (e.g., cisplatin 75 mg/m² day 1 + vinorelbine 25 mg/m² days 1 and 8, every 3 weeks for 4 cycles). The LACE pooled analysis showed a 4% absolute improvement in 5-year survival.
- •For resected EGFR-mutated (exon 19 deletion or L858R) stage IB-IIIA, prescribe adjuvant osimertinib 80 mg orally once daily for 3 years. The ADAURA trial demonstrated a 4-year DFS of 70% versus 29% with placebo (HR 0.23).
- •For resected ALK-positive stage IB-IIIB, prescribe adjuvant ensartinib 225 mg orally once daily for 24 months. The ELEVATE trial showed 24-month DFS of 86.4% versus 53.5% (HR 0.20).
- •For resected RET fusion-positive stage II-IIIA, prescribe adjuvant selpercatinib for 3 years (dose per package insert). The LIBRETTO-432 trial showed 2-year EFS of 92% versus 61% (HR 0.17).
- •For stage II-IIIA with PD-L1 TC ≥1% after chemotherapy, consider adjuvant atezolizumab 1200 mg IV every 3 weeks for 16 cycles. IMpower010 showed DFS benefit (HR 0.70), with pronounced benefit in PD-L1 ≥50% (OS HR 0.47).
- •For stage IB-IIIA regardless of PD-L1, pembrolizumab 200 mg IV every 3 weeks for up to 18 cycles is an alternative (PEARLS/KEYNOTE-091), but it is not yet standard for all subgroups.
- •Perform surgery using minimally invasive approach (VATS or RATS) whenever possible. RATS offers higher lymph node yield and lower conversion rates than VATS, especially after neoadjuvant therapy. Uniportal VATS has shorter hospital stay and lower conversion than multiportal VATS.
- •For central tumors requiring pneumonectomy, consider bronchial sleeve lobectomy to preserve lung parenchyma. RATS for sleeve lobectomy is associated with shorter operative time and less blood loss than open thoracotomy.
- •During surgery, ensure adequate lymph node assessment: sample at least 3 N2 stations and 1 N1 station (the 3+1 rule). This is safe and does not increase complications.
- •Use ERAS protocols: multimodal analgesia, early mobilization, and coaxial chest drains. Coaxial drains reduce drainage duration (4 vs 6 days) and tube occlusion (4% vs 30%).
- •Avoid concurrent bevacizumab with thoracic radiation, it increases the risk of tracheoesophageal fistula (two phase II trials closed early). Consider proton beam therapy when radiation is needed to reduce esophageal toxicity.
- •Refer to medical oncology for all patients with stage II-IIIA disease to discuss neoadjuvant and adjuvant therapy. Refer to radiation oncology for stage IIIB (unresectable) or for patients with N2 disease in whom definitive chemoradiation is preferred.
- •Discharge criteria: chest tube removed with no air leak, pain controlled on oral analgesics, mobilized independently, and afebrile. Follow-up imaging scheduled at 3-6 months postoperatively.
Board Review — High Yield
- •GGO-dominant invasive adenocarcinoma, Systematic mediastinal lymph node dissection can be safely omitted (ECTOP-1009 trial).
- •Stage IB adjuvant chemotherapy, Only indicated for tumors ≥4 cm (CALGB 9633).
- •Neoadjuvant chemo-immunotherapy, Standard of care for stage II-IIIA NSCLC; improves event-free survival and pathologic response.
- •Osimertinib adjuvant, 80 mg daily for 3 years in EGFR-mutated resected NSCLC; 4-year DFS 70% vs 29% (ADAURA).
- •Ensartinib adjuvant, 225 mg daily for 24 months in ALK-positive resected NSCLC; 2-year DFS 86.4% vs 53.5% (ELEVATE).
- •Atezolizumab adjuvant, For PD-L1 TC ≥1% stage II-IIIA after chemotherapy; OS HR 0.47 in PD-L1 ≥50% (IMpower010).
- •EBUS+EUS mediastinal staging, sROC 0.99, recommended as first-line over mediastinoscopy (ERS/ESGE/ESTS).
- •Conversion to thoracotomy, Higher after neoadjuvant therapy (20% MIS); RATS has lower conversion rate than VATS.
- •8-week smoking cessation, Threshold for reducing postoperative pulmonary complications (OR 0.42, specificity 96.55%).
- •Coaxial chest drains, Reduce drainage duration, tube occlusion, and subcutaneous emphysema after VATS lobectomy.
Deep Dive — Evidence Details
Indications by Stage
- ▸Stage I and II NSCLC are resectable with curative intent; stage III is heterogeneous and requires multidisciplinary selection.
- ▸For GGO-dominant lung adenocarcinoma, mediastinal lymph node dissection can be safely omitted based on the ECTOP-1009 trial [15].
- ▸Neoadjuvant or perioperative chemo-immunotherapy is the preferred approach for stage II-IIIA NSCLC, with significant EFS and OS benefits [7,9].
- ▸Adjuvant targeted therapy (osimertinib for EGFR-mutated, ensartinib for ALK-positive) is standard for resected stage IB-IIIB disease [11,19].
Surgical eligibility for (NSCLC) is determined by clinical stage, histologic subtype, molecular profile, and patient fitness. The stage gates for resection with curative intent are defined by the ability to achieve a complete (R0) resection and by the risk-benefit balance of perioperative systemic therapy.
Stage I (T1-T2aN0M0)
Stage I NSCLC is the most favorable surgical cohort. with systematic mediastinal lymph node sampling or dissection remains the standard of care, achieving 5-year survival rates exceeding 70% in contemporary series. For patients with ground-glass opacity (GGO)-dominant invasive lung adenocarcinoma (consolidation-to-tumor ratio ≤0.5, tumor ≤3 cm), the Phase III ECTOP-1009 trial demonstrated that systematic mediastinal lymph node dissection (LND) can be safely omitted, as no mediastinal nodal metastases were found in 151 patients undergoing LND, and the no-LND arm had significantly shorter operative time (mean 74 vs 109 minutes), less blood loss (44 vs 82 mL), and shorter hospital stay (3.9 vs 4.5 days) [15]A1b. For stage IB disease (T2aN0), adjuvant chemotherapy is not standard across the entire cohort. The CALGB 9633 trial, the only RCT designed specifically for stage IB, showed no significant survival benefit for adjuvant plus in the overall population (HR 0.83), but an exploratory analysis revealed a statistically significant advantage for patients with tumors ≥4 cm (HR 0.69) [16]A1b.
Stage II (T1-T2bN1M0, T3N0M0)
Stage II NSCLC is resectable with curative intent. The LACE pooled analysis confirmed that adjuvant -based chemotherapy improves 5-year survival by approximately 4% in resected stage II and IIIA disease, with vinorelbine plus cisplatin offering the highest benefit [10]A1b. For stage II disease, neoadjuvant or perioperative chemo-immunotherapy has become the preferred approach. A meta-analysis of 11 trials found that neoadjuvant/perioperative chemo-immunotherapy significantly improved event-free survival (EFS) compared with chemotherapy alone in stage II NSCLC (HR 0.69, 95% CI 0.54-0.88), whereas adjuvant immunotherapy alone showed no significant EFS benefit in this subgroup (HR 0.81, 95% CI 0.63-1.05) [7]A1a. The RATIONALE-315 trial confirmed that perioperative plus chemotherapy improved overall survival (HR 0.65, 95% CI 0.45-0.93) and EFS (HR 0.58, 95% CI 0.43-0.79) in stage II-IIIA NSCLC [9]A1b.
Stage III (T1-T4N2-3M0)
Stage III disease is heterogeneous. Stage IIIA (N2) is frequently resectable after neoadjuvant therapy, while stage IIIB (N3) is generally unresectable and treated with definitive chemoradiation. The 2nd ESMO Consensus Conference on Lung Cancer recommended that for patients with resectable stage IIIA(N2) NSCLC, induction therapy (chemotherapy or chemo-immunotherapy) followed by surgery is a valid option, and that surgery should only be performed after careful multidisciplinary reassessment [4]A1c. For EGFR-mutated stage II-IIIB NSCLC, the NeoADAURA trial demonstrated that neoadjuvant osimertinib with or without chemotherapy significantly improved major pathologic response rates (26% and 25% vs 2% with chemotherapy alone) and enabled high rates of R0 resection (91-95%) and nodal downstaging (53% for both osimertinib arms vs 21% in controls) [12]A1b. For ALK-positive stage IB-IIIB NSCLC, the ELEVATE trial showed that adjuvant ensartinib (225 mg once daily for 24 months) dramatically improved 24-month disease-free survival compared with placebo (86.4% vs 53.5%; HR 0.20, 95% CI 0.11-0.38) [19]A1b.
Stage IV (M1a-M1b), Limited Role
Surgery in stage IV is reserved for oligometastatic disease (e.g., solitary brain or adrenal metastasis) and is not standard. The available evidence for surgical management in this setting is limited to case series and does not support routine resection outside of clinical trials.
| Stage | Resectability | Preferred Surgical Approach | Perioperative Systemic Therapy | Key Evidence [Ref] |
|---|---|---|---|---|
| IA (T1a-cN0) | Yes | Lobectomy or (GGO-dominant: omit mediastinal LND) | Not indicated | [15]A1b |
| IB (T2aN0) | Yes | Lobectomy | Consider adjuvant chemotherapy if tumor ≥4 cm | [16]A1b |
| IIA-IIB | Yes | Lobectomy or | Neoadjuvant chemo-immunotherapy or adjuvant chemotherapy | [7]A1a[9]A1b[10]A1b |
| IIIA (N2) | Selectively resectable | Lobectomy after induction therapy | Neoadjuvant chemo-immunotherapy; adjuvant targeted therapy if EGFR/ALK+ | [4]A1c[7]A1a[12]A1b |
| IIIB (N3) | Unresectable | None | Definitive chemoradiation + | [17]C4 |
| IV | Rarely (oligometastatic) | Metastasectomy ± primary resection | Systemic therapy | , |
Pearl: For GGO-dominant T1N0M0 invasive lung adenocarcinoma, systematic mediastinal lymph node dissection is unnecessary and may cause harm, omit it [15]A1b. For resected stage II-IIIA NSCLC, neoadjuvant/perioperative chemo-immunotherapy is now the standard of care, superseding upfront surgery [7]A1a.
These stage-based indications lead directly to the specific surgical techniques, lobectomy, segmentectomy, pneumonectomy, and extended resections, which are detailed in the next section.
Operative Techniques
- ▸Combined EBUS-TBNA and EUS-FNA provides the highest diagnostic accuracy for mediastinal staging (sROC 0.99) and is recommended over mediastinoscopy as the initial test.
- ▸Sublobar resection is associated with a small but statistically significant OS disadvantage in stage I NSCLC (HR 1.09), but not in stage IA (HR 1.10, not significant), supporting its use in selected patients.
- ▸RATS consistently yields more lymph node stations than VATS, with comparable perioperative safety; this may improve nodal staging but has not yet shown a survival benefit.
Once the operative candidate is selected, the choice of surgical technique, from mediastinal staging to the extent of parenchymal resection and the minimally invasive platform, directly influences oncologic and perioperative outcomes.
Mediastinal Staging via Endosonography
Accurate mediastinal staging is the first operative step. The combination of and provides the highest diagnostic accuracy, with a summary receiver operating characteristic (sROC) of 0.99, comparable to mediastinoscopy [33]B2a. Individually, EBUS-TBNA (sROC 0.98) and EUS-FNA (sROC 0.96) also demonstrate high accuracy [33]B2a. Based on these data, the European Respiratory Society, European Society of Gastrointestinal Endoscopy, and European Society of Thoracic Surgeons (ERS/ESGE/ESTS) recommend endosonography over mediastinoscopy as the initial test for mediastinal nodal tissue staging [29]A1c. Systematic staging (sampling all accessible stations) is suggested over targeted staging, and combined EBUS-TBNA+EUS(-B)-FNA is preferred over EBUS-TBNA alone [29]A1c. For restaging after induction therapy, endosonography is again recommended over mediastinoscopy [29]A1c. EBUS-TBNA for restaging after induction chemotherapy has a sensitivity of 76%, specificity 100%, and negative predictive value of only 20%; therefore, tumor-negative findings should be confirmed by surgical staging before thoracotomy [38]D5.
Extent of Resection: Versus Sublobar Resection
For stage I NSCLC, the debate between lobectomy and sublobar resection persists. A comprehensive umbrella review of 18 meta-analyses found that for overall survival (OS) in stage I, the pooled hazard ratio was 1.09 (95% CI 1.02-1.16; I²=71.6%) favoring lobectomy, but for stage IA the HR was 1.10 (95% CI 0.99-1.22; I²=77.1%), which did not reach statistical significance [27]A1a. For disease-free survival (DFS), the HR was 1.13 (95% CI 1.04-1.23) for stage I and 1.13 (95% CI 1.01-1.27) for stage IA, both favoring lobectomy albeit with low or very low certainty of evidence [27]A1a. These data suggest that sublobar resection is a reasonable option for carefully selected patients with stage IA disease, particularly those with small tumors and favorable histology, but the evidence is limited by heterogeneity and small-study effects [27]A1a.
Minimally Invasive Approaches: VATS, RATS, and Uniportal Techniques
Minimally invasive lobectomy via or is the standard for early-stage NSCLC. In a meta-analysis of real-world clinical studies (excluding database analyses), RATS was associated with a higher lymph node yield (weighted mean difference +2.38) compared with VATS, but no significant differences in blood loss, length of stay, or complications [35]B2a. For specifically, RATS yielded more lymph node stations examined (mean difference 1.16, 95% CI 0.51-1.81) and a shorter hospital stay (mean difference -0.75 days, 95% CI -1.36 to -0.15) compared with VATS, with no differences in operative time, complications, or readmission [31]B2a. A propensity-matched meta-analysis of 14,007 patients found that RATS segmentectomy had lower intraoperative blood loss (mean difference -8.82 mL, 95% CI -16.37 to -1.28) but similar median OS (4.6 years in both groups; HR 0.98, 95% CI 0.90-1.08) [32]C4.
Uniportal VATS (uVATS) is a less invasive alternative to multiportal VATS. In a meta-analysis of 29 studies (6,708 patients), uVATS was associated with a shorter hospital stay (mean difference -0.87 days, P<0.001) and a lower conversion-to-thoracotomy rate (3.3% vs. 5.1%; OR 0.63, P=0.03) with comparable 1- and 3-year OS and recurrence-free survival [36]B2a.
Sleeve Resection and Complex Bronchoplastic Procedures
For central tumors, bronchial sleeve lobectomy (BSL) is performed to avoid . A Bayesian network meta-analysis comparing RATS, VATS, and open thoracotomy for BSL found that RATS had a shorter operative time, less intraoperative blood loss, and reduced postoperative drainage time, with equivalent long-term survival [37]B2a.
Neoadjuvant Immunochemotherapy and Surgical Feasibility
Neoadjuvant immune checkpoint inhibitor (ICI)-based therapy alters tissue planes, causing hilar fibrosis and vascular friability [25]A1b. In the Neotorch trial, perioperative toripalimab plus chemotherapy reduced the rate of surgery cancellation from 26.7% to 17.8% (P=0.03; NNT = 11 to prevent one cancellation) and increased rates of R0 resection and lymph node downstaging [24]A1b. In a phase II trial of neoadjuvant plus chemotherapy in EGFR-mutant NSCLC, 87.9% achieved R0 resection, and all patients underwent minimally invasive surgery [34]B2b. Retrospective data suggest that RATS may offer advantages in managing ICI-altered anatomy, with lower conversion rates than VATS in experienced hands, though this requires prospective validation [25]A1b.
Lymph Node Assessment and Nodal Yield
Adequate lymph node assessment is critical for accurate staging and adjuvant therapy decisions. RATS consistently demonstrates a higher lymph node yield than VATS, regardless of the type of resection [31]B2a[32]C4[35]B2a. The clinical significance of this difference remains uncertain, as it has not been clearly linked to survival benefit, but it may improve nodal staging accuracy [32]C4.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Mediastinal staging: endosonography vs mediastinoscopy | ERS/ESGE/ESTS recommends endosonography as first-line [29]A1c | Brazilian Group of Thoracic Oncology states mediastinoscopy remains surgical gold standard [33]B2a | High-quality evidence for both | Endosonography is preferred initial test; mediastinoscopy reserved for negative endosonography [33]B2a |
| Lobectomy vs sublobar for stage IA | Pooled HR for OS not significant (HR 1.10, 95% CI 0.99-1.22) [27]A1a | Individual meta-analyses show significant OS benefit for lobectomy in broader stage I | Low certainty | Sublobar resection acceptable for select patients with stage IA; shared decision-making needed |
Pearl: For patients with stage IIIA-N2 disease who have negative endosonography after induction therapy, always confirm with surgical staging before thoracotomy, the negative predictive value of EBUS-TBNA is only 20% [38]D5. For patients with early-stage NSCLC who are candidates for parenchymal-sparing surgery, see the section on Fertility-Sparing Surgery for considerations in reproductive-age women.
| Modality | sROC | Sensitivity | Specificity | PPV | NPV | Accuracy |
|---|---|---|---|---|---|---|
| EBUS-TBNA + EUS-FNA | 0.99 | NR | NR | NR | NR | NR |
| EBUS-TBNA alone | 0.98 | 76%* | 100%* | 100%* | 20%* | 77%* |
| EUS-FNA alone | 0.96 | NR | NR | NR | NR | NR |
| CT | 0.73 | NR | NR | NR | NR | NR |
| PET-CT | 0.87 | NR | NR | NR | NR | NR |
*Values from [38]D5 for restaging after induction chemotherapy. NR = not reported in the source. sROC values from [33]B2a.
Fertility-Sparing Surgery
- ▸No retrieved evidence specifically addresses fertility-sparing surgery in NSCLC; current practice is extrapolated from other tumor types.
- ▸Oncologic priority of complete resection (R0) must not be compromised by fertility-sparing considerations.
- ▸Prospective studies with fertility-related endpoints are needed to inform management of young adults with early-stage NSCLC.
From the preceding discussion of operative techniques, the reader will appreciate that the primary goal of surgical resection in NSCLC is complete oncologic clearance. For young patients with early-stage disease, the additional goal of preserving fertility adds complexity to surgical planning. However, the retrieved evidence does not report any studies specifically evaluating fertility-sparing techniques (e.g., ovarian transposition, uterine preservation, or gonadotropin-releasing hormone agonist use) in the context of NSCLC resection. No data on pregnancy outcomes, ovarian function, or fertility preservation strategies after lung cancer surgery are provided in the available literature. Current practice therefore relies on principles extrapolated from other malignancies and on shared decision-making with the patient, acknowledging that the oncologic priority of complete resection (R0) must not be compromised. The absence of NSCLC-specific evidence underscores a critical gap. Future prospective studies or registries should include fertility-related endpoints to inform management of young adults undergoing curative lung resection. The next section, Sentinel Lymph Node Mapping, discusses a technique that, while not directly addressing fertility, contributes to the precise staging that guides adjuvant therapy decisions and may influence the extent of nodal dissection in younger patients.
Pearl: Prospective studies with fertility-related endpoints are needed to inform management of young adults with early-stage NSCLC.
Sentinel Lymph Node Mapping
- ▸Sentinel lymph node mapping in early-stage NSCLC can be performed with radiotracers (99mTc-MSA, 68Ga-MSA) or ICG-based NIR imaging, achieving detection rates of 80-100% in experienced hands.
- ▸A negative SLN after accurate tracer injection has a 100% negative predictive value for downstream nodal metastases, making it a reliable staging tool.
- ▸Female sex and preserved DLCO (>75% predicted) are independent predictors of successful SLN detection; severe emphysema reduces success.
The transition to parenchymal-sparing resections places a premium on accurate nodal staging, yet 34% of patients with stage IB-IIB NSCLC recur within 3.5 years despite complete mediastinal lymph node dissection [72]C4. Sentinel lymph node (SLN) mapping, the identification of the first tumor-draining lymph node, offers a chance to improve staging precision through focused pathologic examination.
Techniques and Tracers
Multiple approaches have been tested. Lymphoscintigraphy with peritumoral 99mTc-nanocolloid and SPECT/CT visualized nodal activity in only 50% of patients [60]C4. A second-generation radiotracer, 99mTc-MSA, achieved detection rates of 96% with preoperative injection and 97% with intraoperative injection, and intraoperative dosing saved approximately US$607 and 70 minutes per case [69]C4. Gallium-68 MSA for PET/CT produced 100% SLN identification with a mean of 1.9 nodes per patient [62]B2b.
Near-infrared (NIR) fluorescence with indocyanine green (ICG) has become the most widely studied optical technique. In a dose-escalation trial, ICG doses ≥ 1000 μg yielded nearly 90% intrathoracic SLN visualization; no adverse reactions occurred [66]C4. Navigational bronchoscopy-guided peritumoral ICG injection produced an 80% SLN detection rate, and the SLN pathologic status was 100% sensitive and specific for overall nodal status [61]B2b. In a prospective feasibility study, intraoperative transpleural or transbronchial ICG injection identified SLNs in 100% of patients when the injection was accurately placed [72]C4.
| Technique | Tracer | Injection Timing | SLN Detection Rate | Key Finding | Reference |
|---|---|---|---|---|---|
| SPECT/CT | 99mTc-nanocolloid | Pre-operative | 50% | Limited visualization; pleural/systemic activity common | [60]C4 |
| PET/CT | 68Ga-MSA | Pre-operative | 100% | No false-negative SLN in N1/N2 patients | [62]B2b |
| NIR fluorescence | ICG (≥ 1000 μg) | Intra-operative | ~90% | SLN status correlated with final nodal status | [66]C4 |
| NIR + NB-guided | ICG | Intra-operative | 80% | 12.5% upstaging rate; 100% NPV for nodal status | [61]B2b |
| NIR (transpleural/transbronchial) | ICG | Intra-operative | 100% (accurate injection) | Negative SLN predictive of no downstream metastases | [72]C4 |
Detection Accuracy and Upstaging
The SLN procedure reliably identifies the sentinel node when tracer placement is accurate. In patients with a correctly placed injection and a pathology-negative SLN, no downstream metastatic disease was found in any study reporting this metric [61]B2b[62]B2b[72]C4. The presence of metastatic disease in the SLN alone led to 12.5% disease upstaging in one series [61]B2b and 23.5% of patients in another had metastases in the sentinel node [62]B2b. Occult micrometastases were found in 10.8% of analyzed SLNs when rigorous sectioning and cytokeratin staining were applied [76]C4.
Factors Influencing SLN Detection
Patient-related factors affect success. In a multivariate analysis of 65 patients, the factors independently associated with SLN detection were female sex (HR 5.55, 95% CI 1.25-39.33) and DLCO > 75% predicted (HR 4.92, 95% CI 1.27-24.7) [74]C4. Severe emphysema was a significant negative predictor [74]C4. These findings suggest that emphysematous lung parenchyma may impair lymphatic tracer migration.
Impact on Outcomes
Long-term data are limited but promising. In a retrospective analysis of 42 patients, those with a pN0 SLN had a 5-year disease-free survival of 100% versus 66.1% in the non-SLN group, and 5-year overall survival was 100% versus 70.0% [65]C4. The authors concluded that a pN0 SLN may better represent true N0 status than routine sampling.
Controversies and Guideline Disagreement
The role of SLN mapping versus systematic lymph node dissection (SLND) remains debated. A best-evidence review of 12 papers found no significant difference in recurrence rates between SLND and lymph node sampling in stage I NSCLC, but retrospective cohort studies suggested a survival benefit for SLND, likely due to upstaging [79]B3b. The technique is not yet incorporated into major guidelines, and its routine use awaits validation from larger prospective trials.
Pearl: When performed with accurate peritumoral tracer injection and rigorous pathologic evaluation (serial sectioning and cytokeratin staining), a negative SLN has a 100% negative predictive value for downstream nodal disease, providing confidence in stage I designation and potentially guiding the omission of adjuvant therapy.
Adjuvant Therapy Triggers (Post-op Risk Criteria)
- ▸Adjuvant cisplatin-based chemotherapy improves 5-year survival by 4% in stage II-IIIA (NNT 25) but is detrimental in stage IA; for stage IB, benefit is limited to tumors ≥4 cm.
- ▸Molecular drivers (EGFR, ALK, RET) dictate specific targeted adjuvant therapy: osimertinib, aumolertinib, ensartinib, or selpercatinib, each with DFS HRs ~0.17-0.23.
- ▸Adjuvant immunotherapy benefit is clearest in PD-L1 TC ≥50% (atezolizumab) or PD-L1-unselected (pembrolizumab); durvalumab showed no benefit.
Sentinel lymph node mapping identifies the first echelon of nodal drainage; the pathologic status of resected nodes and the primary tumor together dictate the need for adjuvant systemic therapy. The LACE pooled analysis of 4584 patients confirmed a benefit of adjuvant -based chemotherapy (P=0.0043) but showed a detrimental effect in stage IA [10]A1b. The updated individual-patient-data meta-analysis reported an overall 4% absolute improvement in 5-year survival, corresponding to an NNT of 25 [10]A1b.
Stage-Based Chemotherapy Criteria
Resected stage IB NSCLC does not routinely warrant adjuvant chemotherapy. CALGB 9633 found no significant survival benefit in the overall stage IB cohort (HR 0.83, 95% CI 0.64-1.08), but an exploratory analysis showed a significant advantage for tumors ≥4 cm (HR 0.69, 95% CI 0.48-0.99) [16]A1b. Accordingly, NCCN and ASCO guidelines recommend considering adjuvant platinum-based chemotherapy only for stage IB disease with primary tumors ≥4 cm [80]A1c[82]A1b. For stage II-IIIA NSCLC, adjuvant cisplatin-based chemotherapy is standard. The ANITA trial demonstrated a median survival of 65.7 months with vinorelbine plus cisplatin vs 43.7 months with observation (HR 0.80, 95% CI 0.66-0.96; P=0.017), yielding a 5-year absolute survival improvement of 8.6% [88]A1b. The pemetrexed plus cisplatin regimen showed similar efficacy with better tolerability in nonsquamous histology [84]A1b.
| Stage / Biomarker | Recommended Adjuvant Therapy | Key Evidence | NNT (if reported) |
|---|---|---|---|
| IB (≥4 cm) | Consider platinum-based chemotherapy | CALGB 9633 [16]A1b | Not calculable |
| II-IIIA (no driver) | Cisplatin-based chemotherapy (e.g., vinorelbine + cisplatin) | LACE [10]A1b, ANITA [88]A1b | 25 |
| EGFR-mutated (ex19del/L858R), stage IB-IIIA | Osimertinib 80 mg/day × 3 years | ADAURA [11]A1b | Not calculable |
| EGFR-mutated (ex19del/L858R), stage II-IIIB | Aumolertinib 110 mg/day × 3 years | ARTS [89]A1b | Not calculable |
| ALK-positive, stage IB-IIIB | Ensartinib 225 mg/day × 24 months | ELEVATE [19]A1b | Not calculable |
| RET fusion-positive, stage II-IIIA | Selpercatinib × 3 years | LIBRETTO-432 [85]A1b | Not calculable |
| PD-L1 TC ≥1%, stage II-IIIA | 1200 mg q3w × 16 cycles after chemotherapy | IMpower010 [13]A1b | Not calculable |
| PD-L1-unselected, stage IB-IIIA | 200 mg q3w × up to 18 cycles | PEARLS/KEYNOTE-091 [20]A1b | Not calculable |
Molecular Drivers
For resected EGFR-mutated NSCLC, adjuvant osimertinib 80 mg daily for 3 years is standard. In stage II-IIIA, the DFS HR was 0.23 (95% CI 0.18-0.30) with a 4-year DFS rate of 70% vs 29% [11]A1b. The ARTS trial confirmed similar benefit with aumolertinib in stage II-IIIB Chinese patients (HR 0.17, 95% CI 0.09-0.29) [89]A1b. For ALK-positive NSCLC, the ELEVATE trial of ensartinib 225 mg daily for 24 months showed a 24-month DFS of 86.4% vs 53.5% in stage II-IIIB (HR 0.20, 95% CI 0.11-0.38) [19]A1b. For RET fusion-positive NSCLC, the LIBRETTO-432 trial of adjuvant selpercatinib for 3 years improved 2-year EFS from 61% to 92% in stage II-IIIA (HR 0.17, 95% CI 0.06-0.51) [85]A1b.
Immunotherapy Biomarkers
Adjuvant immunotherapy is guided by PD-L1 expression and stage. The IMpower010 trial demonstrated DFS benefit with atezolizumab after chemotherapy in stage II-IIIA PD-L1 TC ≥1% (DFS HR 0.70, 95% CI 0.55-0.91) and pronounced benefit in TC ≥50% (DFS HR 0.48, 95% CI 0.32-0.72; OS HR 0.47, 95% CI 0.28-0.77) [13]A1b. The PEARLS/KEYNOTE-091 trial showed a DFS benefit with pembrolizumab in the overall stage IB-IIIA population regardless of PD-L1 (HR 0.76, 95% CI 0.63-0.91) [20]A1b. In contrast, the BR.31 trial of showed no DFS improvement in the PD-L1 ≥25% subgroup (HR 0.93, 95% CI 0.71-1.25) [83]A1b.
Nodal Disease and PORT
For patients with N2 involvement, the Lung ART trial found that PORT did not significantly improve disease-free survival (3-year DFS 47% vs 44%; HR 0.86, 95% CI 0.68-1.08; P=0.18) and increased cardiopulmonary toxicity (11% vs 5% late grade 3-4) [86]A1b. PORT is not recommended as standard of care in this setting.
Pearl: For stage IB NSCLC, only tumors ≥4 cm warrant adjuvant chemotherapy; the strongest absolute benefit from adjuvant therapy is seen in EGFR-mutated patients receiving osimertinib (4-year DFS 70% vs 29%) and in PD-L1 TC ≥50% stage II-IIIA patients receiving atezolizumab (OS HR 0.47).
Intraoperative Considerations and Complications
- ▸Intraoperative complications are low (3%) after neoadjuvant chemoimmunotherapy, but conversion rates remain elevated (20%); robotic approach reduces conversion risk compared to VATS.
- ▸Frailty, smoking cessation duration (<8 weeks), and elevated blood eosinophil count are modifiable risk factors for intraoperative and postoperative complications.
- ▸The robotic learning curve includes a deceptive plateau phase where operative efficiency improves but complication rates remain elevated until mastery (>137 cases).
Having established postoperative risk criteria, the surgeon must now anticipate and mitigate intraoperative events that can derail an otherwise well-planned resection. Intraoperative complications in NSCLC surgery are infrequent but carry significant consequences; the pooled incidence after neoadjuvant chemoimmunotherapy is 3% [92]A1a. The most common events include bleeding, conversion to thoracotomy, prolonged air leak, and nerve injury, with additional risks from specific treatment combinations.
Intraoperative Bleeding and Conversion
Vascular injury during hilar dissection is the leading cause of emergent conversion. The risk is higher after neoadjuvant therapy due to inflammatory adhesions; meta-analysis reports a pooled intraoperative complication rate of 3% after chemoimmunotherapy [92]A1a. Minimally invasive surgery (MIS) after neoadjuvant treatment carries a 20% conversion rate [92]A1a. The robotic platform reduces conversion risk compared with : adjusted odds ratio 2.47 (95% CI 1.43-4.24) for VATS versus RATS [97]B2b. In a propensity-matched elderly cohort, conversion occurred in 0.9% of RATS cases versus 7.7% of VATS cases (p=0.010) [104]B3b. Prevention relies on careful vessel loop control, low threshold for early conversion, and surgeon experience beyond the learning curve.
Prolonged Air Leak and Bronchial Complications
Air leak persisting beyond 4 days occurred in 14% of VATS and 9% of thoracotomy patients in a randomized trial [90]A1b. Fissureless technique and stapler reinforcement reduce risk. Bronchopleural fistula is rare; in a prospective proton beam series, grade 4 bronchial fistula occurred in 2% of patients [93]B2b. Bronchial stump coverage with intercostal muscle or pericardial fat is standard for high-risk resections (e.g., after neoadjuvant therapy, sleeve ).
Nerve Injury and Chylothorax
Recurrent laryngeal nerve injury complicates left-sided mediastinal dissection, especially in the aortopulmonary window. Transient injury occurred in 2% of patients undergoing subcostal RATS [99]C4. Phrenic nerve palsy is avoided by careful identification during pericardial dissection. Chylothorax frequency is not separately reported in the retrieved evidence but is managed by thoracic duct ligation at the time of injury or postoperatively with dietary modification.
Tracheoesophageal Fistula and Esophageal Toxicity
combined with chemoradiation markedly increases the risk of tracheoesophageal fistula. Two phase II trials closed early due to fistula formation, leading to FDA warnings and a change in bevacizumab labeling [91]B2b. In a phase I/II trial incorporating bevacizumab and erlotinib with concurrent chemoradiation, grade 3-4 esophagitis occurred in 29% of patients, with one grade 3 tracheoesophageal fistula [94]C4. produces lower rates: grade 3 acute esophagitis in 8%, grade 4 esophagitis in 2%, and no grade 5 toxic effects [93]B2b. These data argue against concurrent bevacizumab with thoracic radiation and support for esophageal sparing.
Impact of Patient and Treatment Factors
Preoperative smoking cessation of at least 8 weeks independently reduces postoperative pulmonary complications (OR 0.42, 95% CI 0.17-0.99), with 96.55% specificity for the 8-week threshold [96]B2b. Frailty, measured by the Veterans Affairs Frailty Index, is a strong predictor of major complications (adjusted OR 2.85, 95% CI 2.18-3.71) [106]B3b. Elevated preoperative blood eosinophil count (≥200 cells/µL) is associated with increased 90-day healthcare utilization (adjusted RR 1.52, 95% CI 1.02-2.25) and lower 1-year survival (adjusted HR 2.41, 95% CI 1.08-5.35) [103]B3b. These factors should be addressed preoperatively when possible.
Surgical Approach and Learning Curve
RATS consistently demonstrates advantages over VATS and open thoracotomy: shorter operative time, less blood loss, lower conversion rates, and shorter hospital stay [97]B2b[104]B3b. However, the learning curve for robotic lobectomy exhibits a deceptive plateau. In a 300-patient series, the plateau phase (cases 82-137) showed operative efficiency but persistent 10.7% postoperative complication rates (primarily Clavien-Dindo grade II), which decreased to 3.1% in the mastery phase (>137 cases) [95]B2b. This plateau trap underscores that operative speed alone does not reflect surgical quality. An established VATS program can safely transition to RATS, with fewer severe complications after the first 50 cases (OR 0.17, p=0.026) [105]B3b.
Lymph Node Dissection Safety
The 3+1 rule (sampling at least 3 N2 and 1 N1 stations) is not associated with increased postoperative complications. In a Society of Thoracic Surgeons database study of 28,439 patients, propensity-matched analysis showed no significant differences in arrhythmia, air leak, pneumonia, or 30-day mortality between those who met the 3+1 rule and those who did not [102]B3b. This supports guideline-concordant nodal staging without added surgical risk.
| Complication | Frequency | Prevention | Management |
|---|---|---|---|
| Intraoperative bleeding | 3% (neoadjuvant ICI) [92]A1a; lower with RATS vs VATS [104]B3b | Careful hilar dissection, vascular control, early conversion threshold | Emergent thoracotomy, suture repair, damage control packing |
| Conversion to thoracotomy | 20% MIS after neoadjuvant ICI [92]A1a; VATS 7.7% vs RATS 0.9% [104]B3b | Patient selection, robotic platform, experienced surgeon | Standard thoracotomy, complete resection within same setting |
| Prolonged air leak (>4 days) | 14% VATS, 9% thoracotomy [90]A1b | Fissureless technique, stapler reinforcement, pleural tent | Chest tube management, Heimlich valve, pleurodesis (talc or blood patch) |
| Bronchopleural fistula | 2% grade 4 (proton beam) [93]B2b | Bronchial stump coverage, avoid devascularization | Reoperation, muscle flap, Eloesser flap |
| Tracheoesophageal fistula | Increased with bevacizumab + radiation [91]B2b; grade 3-4 esophagitis 29% [94]C4 | Avoid concurrent bevacizumab with radiation; proton beam therapy | Esophageal stent, surgical repair, diversion |
| Recurrent laryngeal nerve injury | 2% (subcostal RATS) [99]C4 | Avoid excessive traction near aortopulmonary window | Voice therapy, temporary vocal cord injection |
| Arrhythmia | ~1% (VATS and thoracotomy) [90]A1b | Minimize thoracic epidural, correct electrolytes | Beta-blockers, if |
| Chronic pleural effusion (1 year) | 9.7% [101]C4 | Complete lung expansion, early chest tube removal? | Associated with non-cancer mortality; manage underlying wasting |
These intraoperative decisions and complication management directly influence the postoperative course, which is further optimized by ERAS protocols detailed in the next section.
Pearl: The 8-week smoking cessation threshold (96.55% specificity) is a critical inflection point for reducing postoperative pulmonary complications, and frailty assessment using the VA Frailty Index identifies patients at highest risk of major intraoperative and postoperative events [96]B2b[106]B3b.
Postoperative Recovery and ERAS
- ▸ERAS pathways reduce length of stay by 2 days and cardiopulmonary complications by 13% after VATS lobectomy.
- ▸Coaxial chest drains reduce drainage duration, occlusion, and subcutaneous emphysema compared to conventional tubes.
- ▸Acute postoperative pain occurs in ~20% of patients; a nomogram using preoperative factors can predict risk.
Following the intraoperative considerations that minimize surgical stress, the postoperative phase centers on structured recovery pathways that reduce complications and accelerate return to baseline function.
Enhanced Recovery After Surgery (ERAS) Pathways
ERAS protocols have become standard for NSCLC resection. A propensity-matched study of showed that ERAS implementation reduced median length of stay from 7 to 5 days (P=0.004) and decreased cardiopulmonary complication rate by 13% (P=0.044) without increasing readmission [121]B3b. Compliance with ERAS elements averaged 81% [121]B3b.
Chest Drain Management
Effective pleural drainage is critical. A randomized trial of 300 patients undergoing VATS lobectomy compared coaxial drains (dual-channel) with conventional single-lumen tubes. Coaxial drains significantly reduced:
- Drainage duration: 4±2 vs 6±3 days (P=0.04)
- Tube occlusion: 4% vs 30% (P=0.02)
- Subcutaneous emphysema: 38% vs 56% (P=0.03)
- CRP levels from POD 3 onward (P<0.01), indicating reduced inflammation [110]A1b
Another trial found that a drainage ball with low negative pressure reduced pain scores (3.47 vs 6.20, P<0.001) and length of stay (5.40 vs 6.37 days, P=0.045) compared to water-sealed bottles [111]A1b.
Pain Management
Acute postoperative pain (APP) after thoracoscopic lobectomy occurs in about 20% of patients and is associated with chronic pain and pulmonary infections [118]B3b. A nomogram incorporating preoperative analgesic use, smoking history, age, prior thoracic surgery, cancer history, and anxiety status predicted APP with AUC 0.760 [118]B3b. Non-intubated VATS after neoadjuvant therapy reduced postoperative fasting time, inflammatory response, and complications including delirium and respiratory infection [126]C4.
Prehabilitation and Exercise
Multimodal prehabilitation (exercise, nutrition, anxiety reduction) initiated 4 weeks before surgery was as effective as postoperative rehabilitation in recovering functional capacity, with >75% of patients returning to baseline by 8 weeks [107]A1b. However, adding preoperative physical therapy within 3 days of surgery did not reduce 30-day mortality or pulmonary complications compared to postoperative therapy alone [124]B3b. Exercise training after lung resection improves exercise capacity (6MWD MD 57 m, 95% CI 34-80 m) and quadriceps force [114]A1a.
Readmission and Recovery
Despite ERAS, 90-day readmission after VATS is 10.1%, primarily due to pneumonia and pneumothorax [116]B2b. Days alive and out of hospital within 90 days is reduced by a median of 2 days, mainly due to air leak and pain [119]C4.
Prognostic Factors for Recovery
The following table summarizes factors associated with prolonged recovery or complications after NSCLC resection.
| Factor | Good prognosis | Poor prognosis |
|---|---|---|
| Chest drain type | Coaxial drain [110]A1b | Conventional tube [110]A1b |
| Preoperative analgesic use | None [118]B3b | Yes [118]B3b |
| Smoking history | Never [118]B3b | Current/former [118]B3b |
| Age | Younger [118]B3b | Older (>55) [118]B3b |
| Prior thoracic surgery | No [118]B3b | Yes [118]B3b |
| Anxiety | Low [118]B3b | High [118]B3b |
| Sex | Female [116]B2b[119]C4 | Male [116]B2b[119]C4 |
| Lung function | Preserved [119]C4 | Reduced [119]C4 |
| Pleural adhesions | Absent [119]C4 | Present [119]C4 |
| NSCLC diagnosis | Benign/metastasis [119]C4 | NSCLC [119]C4 |
| ERAS pathway | Implemented [121]B3b | Not implemented [121]B3b |
Pearl: Coaxial chest drains and ERAS pathways independently reduce drainage duration and length of stay; combining them optimizes recovery after VATS lobectomy.
These recovery metrics directly inform the outcomes discussed in the next section, where stage-specific survival and recurrence rates are presented.
Outcomes by Stage and Approach
- ▸The provided evidence does not include specific survival, recurrence, or functional outcomes for surgical resection by stage or approach (open vs. MIS).
- ▸For advanced/metastatic NSCLC, modern systemic therapies yield median OS exceeding 2 years in selected populations, with 5-year OS rates of 16-32%.
- ▸Prognostic factors include treatment-related lymphopenia, patient sex, histology, and actionable mutations, which inform treatment selection and outcomes.
Beyond the immediate perioperative period, long-term outcomes after NSCLC resection are determined by pathologic stage, completeness of resection, and the efficacy of any adjuvant therapy. The evidence provided in this section focuses on the survival outcomes of modern systemic therapies for advanced disease, which inform the context for surgical decision-making.
Outcomes by Stage
The provided literature does not report specific survival, recurrence, or functional outcomes for early-stage NSCLC treated with surgery alone or by surgical approach (open vs. minimally invasive). For patients with locally advanced (stage III) disease, the NCCN guidelines recommend multimodality therapy, but the included studies do not provide stage-specific surgical outcomes [127]A1c.
For advanced/metastatic (stage IV) NSCLC, the evidence from multiple phase III trials demonstrates substantial improvements in overall survival (OS) and progression-free survival (PFS) with modern systemic therapies. The table below summarizes key survival outcomes from these trials.
| Trial | Regimen | Median OS | Hazard Ratio | 5-Year OS Rate | Population |
|---|---|---|---|---|---|
| KEYNOTE-024 [136]A1b | vs. chemo | 26.3 vs. 13.4 mo | 0.62 (0.48-0.81) | 31.9% vs. 16.3% | PD-L1 ≥50% |
| KEYNOTE-189 [138]A1b | Pembrolizumab + pemetrexed-platinum vs. placebo + chemo | 22.0 vs. 10.7 mo | 0.56 (0.45-0.70) | Not reported | Nonsquamous, any PD-L1 |
| CheckMate 227 [137]A1b | + vs. chemo | 5-yr OS 24% vs. 14% (PD-L1 ≥1%); 19% vs. 7% (PD-L1 <1%) | Not applicable | 24% vs. 14% (PD-L1 ≥1%) | PD-L1 ≥1% and <1% |
| CheckMate 9LA [146]A1b | Nivolumab + ipilimumab + chemo vs. chemo | 6-yr OS 16% vs. 10% | 0.74 (0.63-0.87) | 16% vs. 10% at 6 yr | Any PD-L1, any histology |
| CROWN (lorlatinib) [134]A1b | Lorlatinib vs. crizotinib | Median PFS not reached vs. 9.1 mo | 0.19 (0.13-0.27) for PFS | 60% vs. 8% at 5 yr | ALK+ advanced |
| TROPION-Lung01 [133]A1b | Dato-DXd vs. | 12.9 vs. 11.8 mo | 0.94 (0.78-1.14) | Not reported | Previously treated, nonsquamous histology benefited |
| RATIONALE-307 [145]A1b | + chemo vs. chemo | HR 0.68 (0.46-1.01) and 0.75 (0.50-1.12) | Not significant | Not reported | Squamous, first-line |
Prognostic Factors
Several factors influence outcomes beyond stage. Severe treatment-related lymphopenia (<500 cells/mm³) after chemoradiation is associated with increased risk of death (HR 1.7 in lung cancer cohort; overall HR 2.1, 95% CI 1.54-2.78) [130]B2a. Patient sex also modifies the efficacy of immune checkpoint inhibitors: pooled OS HR was 0.72 (0.65-0.79) in men and 0.86 (0.79-0.93) in women (p=0.0019) [144]A1a. Histology matters: in TROPION-Lung01, Dato-DXd showed benefit in nonsquamous (median PFS 5.5 vs. 3.6 mo; HR 0.63) but not in squamous histology (HR 1.41) [133]A1b. For patients with EGFR-mutated NSCLC who progress on tyrosine kinase inhibitors, a network meta-analysis identified ICI plus antiangiogenesis plus chemotherapy as the optimal strategy, with a PFS HR of 0.54 (0.44-0.67) versus chemotherapy [143]A1a.
Outcomes by Surgical Approach
The provided evidence does not contain data comparing open versus minimally invasive surgical approaches for NSCLC. However, the ASCO-SNO-ASTRO guideline recommends surgery for patients with , particularly those with large tumors and mass effect, though it does not specify outcomes by approach [132]A1a.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Optimal first-line therapy for PD-L1 ≥50% | Pembrolizumab monotherapy (NCCN Category 1) [127]A1c | Nivolumab + ipilimumab + chemo also effective [146]A1b | Both are standard options | Choice depends on tumor burden, patient preference, and toxicity profile |
Pearl: For advanced NSCLC, the survival benefit of modern immunotherapy- and targeted therapy-based regimens is substantial, and these outcomes should be discussed with patients when considering surgical resection for early-stage disease, as the curability of surgery remains the primary determinant of long-term survival, with 5-year OS rates exceeding 60% in resected stage I disease, though the provided evidence does not report these specific surgical outcomes.
Related Pages
Part of the Non-Small Cell Lung Cancer family. Cross-cutting management is split across dedicated child pages:
- , diagnostic page (definition, epidemiology, staging, biomarkers, prognosis)
- Non-Small Cell Lung Cancer Radiation Management , EBRT + image-guided brachytherapy + concurrent chemoradiation, dose / fractionation, OAR constraints
- Non-Small Cell Lung Cancer Systemic Therapy , concurrent / adjuvant / metastatic chemotherapy, targeted therapy, immune checkpoint inhibitors
- Non-Small Cell Lung Cancer Palliative Care , early integration, symptom management, palliative procedures, end-of-life care
- , post-treatment surveillance schedule, late toxicity, survivorship, patient counselling
- Non-Small Cell Lung Cancer Recurrent and Metastatic Disease , local-regional salvage, distant metastatic systemic therapy, oligometastatic disease
Pearl: Use these links to hop between management modalities; the parent Non-Small Cell Lung Cancer page carries diagnosis + staging that informs every decision here.
References
- [1]
Reid E, Suneja G, Ambinder RF et al.. “Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2018). PMID: 30099375 ↗
L1GUIDELINECited in: Indications by Stage, Intraoperative Considerations and Complications - [2]
Jazieh AR, Bamefleh H, Demirkazik A et al.. “Modification and implementation of NCCN guidelines on non-small cell lung cancer in the Middle East and North Africa region.” Journal of the National Comprehensive Cancer Network : JNCCN (2010). PMID: 20697125 ↗
L1GUIDELINECited in: Indications by Stage - [3]
Brodowicz T, Ciuleanu T, Crawford J et al.. “Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2011). PMID: 21940784 ↗
L1GUIDELINECited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [4]
Eberhardt WE, De Ruysscher D, Weder W et al.. “2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology (2015). PMID: 25897013 ↗
L1GUIDELINECited in: Indications by Stage - [5]
Vansteenkiste J, Crinò L, Dooms C et al.. “2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up.” Annals of oncology : official journal of the European Society for Medical Oncology (2014). PMID: 24562446 ↗
L1GUIDELINECited in: Indications by Stage - [6]
Cavalheri V, Tahirah F, Nonoyama M et al.. “Exercise training for people following lung resection for non-small cell lung cancer - a Cochrane systematic review.” Cancer treatment reviews (2013). PMID: 24268442 ↗
L1SR_MA_RCTCited in: Indications by Stage - [7]
Rossi G, Barcellini L, Tagliamento M et al.. “Immunotherapy for resectable NSCLC: neoadjuvant/perioperative followed by surgery over surgery followed by adjuvant. Systematic review and meta-analysis with subgroup analyses.” ESMO open (2025). PMID: 40913837 ↗
L1SR_MA_RCTCited in: Indications by Stage - [8]
Felip E, Altorki N, Zhou C et al.. “Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial.” Annals of oncology : official journal of the European Society for Medical Oncology (2023). PMID: 37467930 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [9]
Wang C, Wang W, Liu H et al.. “Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer: final analysis of the randomized RATIONALE-315 trial.” Annals of oncology : official journal of the European Society for Medical Oncology (2025). PMID: 41344593 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [10]
Le Chevalier T. “Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going?” Annals of oncology : official journal of the European Society for Medical Oncology (2010). PMID: 20943614 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [11]
Herbst RS, Wu YL, John T et al.. “Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023). PMID: 36720083 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [12]
He J, Tsuboi M, Weder W et al.. “Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40454705 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [13]
Felip E, Altorki N, Zhou C et al.. “Five-Year Survival Outcomes With Atezolizumab After Chemotherapy in Resected Stage IB-IIIA Non-Small Cell Lung Cancer (IMpower010): An Open-Label, Randomized, Phase III Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40446184 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [14]
Awad MM, Forde PM, Girard N et al.. “Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 39778121 ↗
L1RCTCited in: Indications by Stage - [15]
Zhang Y, Qian B, Song Q et al.. “Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity-Dominant Lung Adenocarcinoma.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2025). PMID: 40690727 ↗
L1RCTCited in: Indications by Stage - [16]
Strauss GM, Herndon JE, Maddaus MA et al.. “Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008). PMID: 18809614 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [17]
Allignet B, De Ruysscher D, Martel-Lafay I et al.. “Stereotactic body radiation therapy in unresectable stage III non-small cell lung cancer: A systematic review.” Cancer treatment reviews (2023). PMID: 37210766 ↗
L4SR_COHORTCited in: Indications by Stage - [18]
Wink KCJ, van Baardwijk A, Troost EGC et al.. “Nodal recurrence after stereotactic body radiotherapy for early stage non-small cell lung cancer: Incidence and proposed risk factors.” Cancer treatment reviews (2017). PMID: 28437679 ↗
L2SR_COHORTCited in: Indications by Stage - [19]
Yue D, Huang M, Song P et al.. “Ensartinib in Resected ALK-Positive Non-Small-Cell Lung Cancer.” The New England journal of medicine (2026). PMID: 42418775 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [20]
O'Brien M, Paz-Ares L, Marreaud S et al.. “Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial.” The Lancet. Oncology (2022). PMID: 36108662 ↗
L1RCTCited in: Indications by Stage, Adjuvant Therapy Triggers (Post-op Risk Criteria) - [21]
Kanwar N, Seyi AB, Tan N et al.. “From Diagnosis, Therapy Decision-Making to Genetic Risk Assessment: The Impact of ctDNA Testing on Comprehensive Cancer Management-A Case Report.” Journal of the National Comprehensive Cancer Network : JNCCN (2025). PMID: 41671451 ↗
L4CASE_SERIESCited in: Operative Techniques - [22]
Thomas A, Rajan A, Lopez-Chavez A et al.. “From targets to targeted therapies and molecular profiling in non-small cell lung carcinoma.” Annals of oncology : official journal of the European Society for Medical Oncology (2012). PMID: 23131389 ↗
L5NARRATIVE_REVIEWCited in: Operative Techniques - [23]
Donington J, Schumacher L, Yanagawa J. “Surgical Issues for Operable Early-Stage Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 34985938 ↗
L5NARRATIVE_REVIEWCited in: Operative Techniques - [24]
Fang W, Wang Y, Wang W et al.. “Surgical Outcomes of Perioperative Toripalimab in Stage III Resectable Non-Small Cell Lung Cancer: Post Hoc Analysis of the Neotorch Randomized Clinical Trial.” JAMA surgery (2026). PMID: 42455561 ↗
L1RCTCited in: Operative Techniques - [25]
Magouliotis DE, Androutsopoulou V, Cioffi U et al.. “Robotic-Assisted Thoracic Surgery in the Immunotherapy Era: Navigating Altered Anatomy, Oncologic Precision, and the Future of Integrated Platforms.” Journal of clinical medicine (2026). PMID: 42355653 ↗
L1RCTCited in: Operative Techniques - [26]
Morrow CJ, Trapani F, Metcalf RL et al.. “Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.” Annals of oncology : official journal of the European Society for Medical Oncology (2016). PMID: 27013395 ↗
L4CASE_SERIESCited in: Operative Techniques - [27]
Lin X, Zhang J, Wang B et al.. “Lobectomy versus sublobar resection for stage I non-small cell lung cancer: an umbrella review of evidence quality, overlap, surgical-extent heterogeneity, and survival outcomes.” Frontiers in oncology (2026). PMID: 42326346 ↗
L1SR_MA_RCTCited in: Operative Techniques - [28]
Marinello A, Tagliamento M, Pagliaro A et al.. “Circulating tumor DNA to guide diagnosis and treatment of localized and locally advanced non-small cell lung cancer.” Cancer treatment reviews (2024). PMID: 38963991 ↗
L5NARRATIVE_REVIEWCited in: Operative Techniques - [29]
Korevaar DA, Kovacevic B, Papadopoulou E et al.. “ERS/ESGE/ESTS clinical practice guidelines on endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer.” The European respiratory journal (2026). PMID: 42167778 ↗
L1GUIDELINECited in: Operative Techniques - [30]
Babel S, Baral S, Peeran SRH et al.. “Systematic review of extracellular vesicle-based liquid biopsy for leptomeningeal metastasis: current evidence and future directions.” Clinical & experimental metastasis (2026). PMID: 42484930 ↗
L2SR_COHORTCited in: Operative Techniques, Fertility-Sparing Surgery - [31]
Yu YH, Huang YP, Yu AB et al.. “Perioperative outcomes and nodal station assessment after robotic-assisted versus video-assisted thoracoscopic segmentectomy for early-stage NSCLC: a systematic review and meta-analysis.” Journal of robotic surgery (2026). PMID: 42474630 ↗
L2SR_COHORTCited in: Operative Techniques, Intraoperative Considerations and Complications - [32]
Anosike UG, Oliveira Amador WF, Cruz de Assis TC et al.. “Outcomes of robotic vs video-assisted thoracoscopic segmentectomy in early-stage NSCLC: A meta-analysis of propensity-matched studies.” Lung cancer (Amsterdam, Netherlands) (2026). PMID: 42456640 ↗
L4SR_COHORTCited in: Operative Techniques - [33]
Baldotto C, Mascarenhas E, Gelatti ACZ et al.. “Staging Modalities in Non-Small Cell Lung Cancer: Evidence-Based Guideline and Systematic Review by the Brazilian Group of Thoracic Oncology.” Clinical lung cancer (2026). PMID: 42114171 ↗
L2SR_COHORTCited in: Operative Techniques - [34]
Zhang C, Jiang BY, Yan LX et al.. “Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant non-small cell lung cancer (NEOTIDE/CTONG2104): phase II trial and correlative genomic analysis in China.” EClinicalMedicine (2026). PMID: 42256683 ↗
L2NON_RANDOMIZED_TRIALCited in: Operative Techniques - [35]
Zhu J, Meng X, Hu L. “Perioperative outcomes of robot-assisted versus video-assisted thoracoscopic surgery for non-small cell lung cancer: a meta-analysis focusing on real-world clinical studies in the past 10 years.” Frontiers in oncology (2026). PMID: 42232542 ↗
L2SR_COHORTCited in: Operative Techniques - [36]
Wilson-Smith AR, Ali A, Bebawi M et al.. “Comparative outcomes of uniportal and multiportal video-assisted thoracoscopic surgery-a systematic review and meta-analysis.” Journal of thoracic disease (2026). PMID: 42182625 ↗
L2SR_COHORTCited in: Operative Techniques - [37]
Wang C, Qiao L, Xu Y et al.. “Robotic Surgery for Bronchial Sleeve Lobectomy: A Systematic Review and Bayesian Network Meta-Analysis.” The international journal of medical robotics + computer assisted surgery : MRCAS (2026). PMID: 42140880 ↗
L2SR_COHORTCited in: Operative Techniques, Intraoperative Considerations and Complications - [38]
Herth FJ, Annema JT, Eberhardt R et al.. “Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum in lung cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008). PMID: 18519953 ↗
L5OTHERCited in: Operative Techniques - [39]
Bu F, Jin ZY, Ling ZQ. “Plasma HERV-K envelopE RNA: a minimally invasive biomarker for lung adenocarcinoma detection and prognostic assessment in the context of conventional serum tumor markers.” Frontiers in immunology (2026). PMID: 42459690 ↗
L2PROSPECTIVE_COHORTCited in: Operative Techniques - [40]
Feng S, Feng Z, Xie S et al.. “Plasma proteomics predicts pathological complete response and reveals LIF as a potential mediator of resistance to neoadjuvant immunochemotherapy in resectable NSCLC.” Journal for immunotherapy of cancer (2026). PMID: 42425715 ↗
L2PROSPECTIVE_COHORTCited in: Operative Techniques - [41]
Perrotta N, Coluccia A, Rossi F et al.. “Pharmacoeconomic Analysis of Osimertinib Compared to Earlier-Generation EGFR Inhibitors in EGFR-Mutated NSCLC: A Systematic Review.” Cancer medicine (2026). PMID: 42484063 ↗
L2SR_COHORTCited in: Fertility-Sparing Surgery - [42]
Lu R, Lin A, Jiang A et al.. “An interpretable multi-task whole-slide histopathology AI model for non-small cell lung cancer: Cross-cohort generalisation, spatial attention-transcriptomic integration, and molecular-immune profiling.” Clinical and translational medicine (2026). PMID: 42494157 ↗
L2PROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [43]
Yuan T. “Safety-aware AI for NSCLC trial pre-screening: a comparative proof-of-concept study of rule-based, single-agent, and multi-agent approaches.” International journal of medical informatics (2026). PMID: 42485959 ↗
L2PROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [44]
Homeniuk A, Syed A, Atrash A. “Survival Outcomes Associated With Prolonged Pembrolizumab After Definitive Chemoradiation for Non-small Cell Lung Cancer.” Clinical oncology (Royal College of Radiologists (Great Britain)) (2026). PMID: 42476036 ↗
L4PROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [45]
Li L, Liu Y, Wu Z et al.. “Internal Validity-Gated Dual Weighting: Toward Target Validity in the Synthesis of Randomized Controlled Trials and Real-World Studies.” Journal of evidence-based medicine (2026). PMID: 42483848 ↗
L1RCTCited in: Fertility-Sparing Surgery - [46]
Mastrantoni L, Vitale A, Russo J et al.. “Design-Outcome Concordance in Targeted-Therapy trials in Non-Small cell lung cancer: a Meta-Research study.” Journal of the National Cancer Institute (2026). PMID: 42477876 ↗
L1RCTCited in: Fertility-Sparing Surgery - [47]
Izadpanah K, Rezaei M, Nejadghaderi SA et al.. “Efficacy and Safety of Canakinumab Compared With Standard Therapy for the Treatment of Non-Small Cell Lung Cancer (NSCLC): A Systematic Review.” Cancer reports (Hoboken, N.J.) (2026). PMID: 42486074 ↗
L2SR_COHORTCited in: Fertility-Sparing Surgery - [48]
Chen W, Liang Y, Hou Q et al.. “Risk stratification model based on estimated dose of radiation to immune cells and radiotherapy-related nadir lymphocyte count for predicting the efficacy of consolidation immunotherapy in stage III non-small cell lung cancer.” Frontiers in immunology (2026). PMID: 42495622 ↗
L3COHORTCited in: Fertility-Sparing Surgery - [49]
Du X, Luo X, Zhang H et al.. “Price trend, clinical benefit and within-class competition of drugs for metastatic Non-small cell lung cancer in China: a retrospective cohort study.” The Lancet regional health. Western Pacific (2026). PMID: 42495089 ↗
L3RETROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [50]
Zhang Z, Tao X, Ju H et al.. “Adding local gyro-knife radiotherapy to EGFR-TKI improves outcomes in EGFR-mutant NSCLC.” European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (2026). PMID: 42492466 ↗
L3RETROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [51]
Hansford RLW, Davis LE, Griffiths R et al.. “Receipt of cancer care among stage IV non-small-cell lung cancer patients with and without intellectual or developmental disabilities: A population-based retrospective cohort study.” Palliative medicine (2026). PMID: 42490651 ↗
L3RETROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [52]
Liu D, Yang S, Chen Y et al.. “Precision Stereotactic Body Radiotherapy for Ultra-Central NSCLC: Tailored Margins Reduce Toxicity Without Compromising Tumor Control.” MedComm (2026). PMID: 42488704 ↗
L3COHORTCited in: Fertility-Sparing Surgery - [53]
Lee JH, Song HH, Gu BM et al.. “Single-port robotic segmentectomy using the da Vinci SP system for non-small cell lung cancer.” Frontiers in surgery (2026). PMID: 42482943 ↗
L2PROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [54]
Morita S, Mimae T, Kudo Y et al.. “Local Control by Mediastinal Lymph-Node Dissection in Stage I Non-Small-Cell Lung Cancer.” Interdisciplinary cardiovascular and thoracic surgery (2026). PMID: 42479154 ↗
L2PROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [55]
Nakatsui M, Nishida Y, Nozue S et al.. “Feasibility of Reconstructing Survival Outcomes from Unstructured Electronic Medical Records under Japan's Next-Generation Medical Infrastructure Act: A Historical Cohort Study of Atezolizumab in Non-small Cell Lung Cancer.” Drugs - real world outcomes (2026). PMID: 42489799 ↗
L4COHORTCited in: Fertility-Sparing Surgery - [56]
Hodroj MH, Numan H, El-Halabi L et al.. “Impact of Lack of Access to Immunotherapy on Survival in Stage IV Non-Small Cell Lung Cancer: A Multicenter Retrospective Study From Lebanon.” JCO global oncology (2026). PMID: 42485593 ↗
L3RETROSPECTIVE_COHORTCited in: Fertility-Sparing Surgery - [57]
Zhang L, Huang L, Huang D et al.. “Safety and Efficacy of Aumolertinib as First-Line Treatment in EGFR-Mutant Lung Adenosquamous Carcinoma: A Multicenter, Single-Arm, Prospective Phase II Study (ARISE Study).” MedComm (2026). PMID: 42488708 ↗
L2NON_RANDOMIZED_TRIALCited in: Fertility-Sparing Surgery - [58]
Jones S, Falchook G, Graff S et al.. “A Phase II Study to Evaluate the Efficacy of Commercially Available Molecularly Matched Targeted Therapies in the Second-Line Setting.” The oncologist (2026). PMID: 42485262 ↗
L2NON_RANDOMIZED_TRIALCited in: Fertility-Sparing Surgery - [59]
Skoulidis F, Jabbour SK, Garon EB et al.. “Utilizing machine learning to identify multimodal signatures for patients who would benefit from the addition of tremelimumab to durvalumab and chemotherapy (TRIDENT).” Clinical cancer research : an official journal of the American Association for Cancer Research (2026). PMID: 42485106 ↗
L2NON_RANDOMIZED_TRIALCited in: Fertility-Sparing Surgery - [60]
Abele JT, Allred K, Clare T et al.. “Lymphoscintigraphy in early-stage non-small cell lung cancer with technetium-99m nanocolloids and hybrid SPECT/CT: a pilot project.” Annals of nuclear medicine (2014). PMID: 24557659 ↗
L4RCTCited in: Sentinel Lymph Node Mapping - [61]
Hachey KJ, Digesu CS, Armstrong KW et al.. “A novel technique for tumor localization and targeted lymphatic mapping in early-stage lung cancer.” The Journal of thoracic and cardiovascular surgery (2017). PMID: 28274559 ↗
L2NON_RANDOMIZED_TRIALCited in: Sentinel Lymph Node Mapping - [62]
Eo JS, Kim HK, Kim S et al.. “Gallium-68 neomannosylated human serum albumin-based PET/CT lymphoscintigraphy for sentinel lymph node mapping in non-small cell lung cancer.” Annals of surgical oncology (2014). PMID: 25155392 ↗
L2NON_RANDOMIZED_TRIALCited in: Sentinel Lymph Node Mapping - [63]
Nomori H, Mori T, Ikeda K et al.. “Segmentectomy for selected cT1N0M0 non-small cell lung cancer: a prospective study at a single institute.” The Journal of thoracic and cardiovascular surgery (2012). PMID: 22502969 ↗
L2NON_RANDOMIZED_TRIALCited in: Sentinel Lymph Node Mapping - [64]
Dalmeijer SWR, Zweedijk BE, Boldewijn DF et al.. “Evaluating the utility of ICG-based NIR imaging for small intestine neuroendocrine tumors: Challenges and the need for tumor-specific tracers.” Surgical oncology (2026). PMID: 42150271 ↗
L4PROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [65]
Digesu CS, Hachey KJ, Gilmore DM et al.. “Long-term outcomes after near-infrared sentinel lymph node mapping in non-small cell lung cancer.” The Journal of thoracic and cardiovascular surgery (2017). PMID: 29248292 ↗
L4PHASE_1_TRIALCited in: Sentinel Lymph Node Mapping - [66]
Gilmore DM, Khullar OV, Jaklitsch MT et al.. “Identification of metastatic nodal disease in a phase 1 dose-escalation trial of intraoperative sentinel lymph node mapping in non-small cell lung cancer using near-infrared imaging.” The Journal of thoracic and cardiovascular surgery (2013). PMID: 23790404 ↗
L4PHASE_1_TRIALCited in: Sentinel Lymph Node Mapping - [67]
Lilburn P, Kwan J, Williamson J et al.. “Endobronchial indocyanine green instillation to identify the intersegmental plane for successful segmentectomy.” Respirology case reports (2023). PMID: 37342249 ↗
L1RCTCited in: Sentinel Lymph Node Mapping - [68]
Ost DE, Niu J, Elting LS et al.. “Quality gaps and comparative effectiveness in lung cancer staging and diagnosis.” Chest (2014). PMID: 24091637 ↗
L3RETROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [69]
Kim HK, Kim S, Sung HK et al.. “Comparison between preoperative versus intraoperative injection of technetium-99 m neomannosyl human serum albumin for sentinel lymph node identification in early stage lung cancer.” Annals of surgical oncology (2011). PMID: 22143575 ↗
L4COHORTCited in: Sentinel Lymph Node Mapping - [70]
Browne IL, Patel YS, Hanna NM et al.. “Three-dimensional virtual lung reconstruction in robotic segmentectomy: A safety and feasibility trial.” JTCVS techniques (2024). PMID: 39991293 ↗
L4PROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [71]
Bae SY, Kim DH, Yun T et al.. “Long-Term Outcomes of Indocyanine Green Versus Inflation-Deflation for Intersegmental Plane Identification in Segmentectomy for Early-Stage Lung Cancer.” Interdisciplinary cardiovascular and thoracic surgery (2026). PMID: 42386676 ↗
L3COHORTCited in: Sentinel Lymph Node Mapping - [72]
Ter Woerds DKM, Verhoeven RLJ, van der Heide SM et al.. “Feasibility of intraoperative indocyanine green injection to identify lymph nodes at risk of metastatic disease for early-stage lung cancer.” JTCVS techniques (2025). PMID: 40814677 ↗
L4COHORTCited in: Sentinel Lymph Node Mapping - [73]
Li Y, Cao Y, Chen Y et al.. “Comparison of watershed analysis with indocyanine green fluorescence staining and modified inflation-deflation method in single-port thoracoscopic complex pulmonary segmentectomy.” Journal of thoracic disease (2024). PMID: 39678874 ↗
L4RETROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [74]
Wollbrett C, Seitlinger J, Stasiak F et al.. “Clinicopathological factors associated with sentinel lymph node detection in non-small-cell lung cancer.” Journal of cardiothoracic surgery (2024). PMID: 38504315 ↗
L4COHORTCited in: Sentinel Lymph Node Mapping - [75]
Rudondy Q, Frey S, Bentellis I et al.. “Impact of indocyanine green on prolonged air leak in minimally invasive segmentectomy.” Thoracic cancer (2024). PMID: 38494909 ↗
L3COHORTCited in: Sentinel Lymph Node Mapping - [76]
Seitlinger J, Stasiak F, Piccoli J et al.. “What is the appropriate "first lymph node" in the era of segmentectomy for non-small cell lung cancer?” Frontiers in oncology (2023). PMID: 36776360 ↗
L4RETROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [77]
Wu Z, Zhang L, Zhao XT et al.. “Localization of subcentimeter pulmonary nodules using an indocyanine green near-infrared imaging system during uniportal video-assisted thoracoscopic surgery.” Journal of cardiothoracic surgery (2021). PMID: 34362399 ↗
L4COHORTCited in: Sentinel Lymph Node Mapping - [78]
Yotsukura M, Okubo Y, Yoshida Y et al.. “Indocyanine green imaging for pulmonary segmentectomy.” JTCVS techniques (2021). PMID: 34318180 ↗
L4RETROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [79]
Mitsos S, Panagiotopoulos N, Patrini D et al.. “Is systematic lymph node dissection mandatory or is sampling adequate in patients with stage I non-small-cell lung cancer?” Interactive cardiovascular and thoracic surgery (2019). PMID: 30496413 ↗
L3RETROSPECTIVE_COHORTCited in: Sentinel Lymph Node Mapping - [80]
Ettinger DS, Wood DE, Aisner DL et al.. “NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.” Journal of the National Comprehensive Cancer Network : JNCCN (2023). PMID: 37015337 ↗
L1GUIDELINECited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [81]
Lu S, Ahn MJ, Reungwetwattana T et al.. “Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study.” Annals of oncology : official journal of the European Society for Medical Oncology (2024). PMID: 39289145 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [82]
Daly ME, Singh N, Ismaila N et al.. “Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021). PMID: 34936470 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [83]
Goss GD, Darling GE, Westeel V et al.. “Adjuvant Durvalumab in Completely Resected Early-Stage Non-Small Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026). PMID: 41529222 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [84]
Kenmotsu H, Yamamoto N, Yamanaka T et al.. “Randomized Phase III Study of Pemetrexed Plus Cisplatin Versus Vinorelbine Plus Cisplatin for Completely Resected Stage II to IIIA Nonsquamous Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2020). PMID: 32407216 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [85]
Wu YL, Hochmair M, Yang Y et al.. “Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer.” The New England journal of medicine (2026). PMID: 42223087 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [86]
Le Pechoux C, Pourel N, Barlesi F et al.. “Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial.” The Lancet. Oncology (2021). PMID: 34919827 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [87]
Rosell R, Carcereny E, Gervais R et al.. “Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.” The Lancet. Oncology (2012). PMID: 22285168 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [88]
Douillard JY, Rosell R, De Lena M et al.. “Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial.” The Lancet. Oncology (2006). PMID: 16945766 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [89]
Zhang L, Zhang X, Wu L et al.. “Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial.” The Lancet. Oncology (2026). PMID: 41539318 ↗
L1RCTCited in: Adjuvant Therapy Triggers (Post-op Risk Criteria) - [90]
Bendixen M, Jørgensen OD, Kronborg C et al.. “Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial.” The Lancet. Oncology (2016). PMID: 27160473 ↗
L1RCTCited in: Intraoperative Considerations and Complications - [91]
Spigel DR, Hainsworth JD, Yardley DA et al.. “Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2009). PMID: 19901100 ↗
L2NON_RANDOMIZED_TRIALCited in: Intraoperative Considerations and Complications - [92]
Bertoglio P, Gallina FT, Balzani E et al.. “Surgical outcomes after neoadjuvant chemoimmunotherapy for resectable NSCLC: a systematic review and meta-analysis.” European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (2026). PMID: 42000405 ↗
L1SR_MA_RCTCited in: Intraoperative Considerations and Complications - [93]
Chang JY, Verma V, Li M et al.. “Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study.” JAMA oncology (2017). PMID: 28727865 ↗
L2NON_RANDOMIZED_TRIALCited in: Intraoperative Considerations and Complications - [94]
Socinski MA, Stinchcombe TE, Moore DT et al.. “Incorporating bevacizumab and erlotinib in the combined-modality treatment of stage III non-small-cell lung cancer: results of a phase I/II trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2012). PMID: 23045594 ↗
L4PHASE_1_TRIALCited in: Intraoperative Considerations and Complications - [95]
Lin YQ, Yang MZ, Cai JS et al.. “Beware of the plateau trap: a multidimensional analysis redefining the learning curve of robotic lobectomy in non-small cell lung cancer.” Journal of robotic surgery (2026). PMID: 42322386 ↗
L2PROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [96]
Çelik B, İşevi C, Pirzirenli MG et al.. “Impact of Smoking Cessation Duration on Postoperative Complications in Lung Cancer Surgery.” The Journal of surgical research (2026). PMID: 42241832 ↗
L2PROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [97]
Mazzali C, Buzzoni C, Grignani F et al.. “Robotic vs thoracoscopic vs open lobectomy and segmentectomy for lung cancer: a multicenter cohort study in the ATS of Milan.” Journal of robotic surgery (2026). PMID: 42237053 ↗
L2PROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [98]
Wang Z, Gonzalez-Rivas D, Yu J et al.. “Uniportal Robotic-Assisted Sleeve Resections in a High-Volume Centre: Technique and Results.” European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (2026). PMID: 42102244 ↗
L2PROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [99]
Yoon DK, Jung W, Jeon JH et al.. “Early outcomes of subcostal four-arm robotic pulmonary resection and mediastinal lymph node dissection for non-small cell lung cancer.” Journal of robotic surgery (2026). PMID: 41572024 ↗
L4PROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [100]
Fraile Olivero CA, Sotillo Valenzuela L, Albarrán Vidal V et al.. “Fissios and postoperative complications (FPoC trial): a multicentre, randomised, controlled clinical trial.” BMJ open respiratory research (2026). PMID: 42303312 ↗
L1RCTCited in: Intraoperative Considerations and Complications - [101]
Tsukamoto Y, Nakada T, Watanabe Y et al.. “Chronic pleural effusion one year after lung cancer surgery is associated with non-cancer mortality and postoperative nutritional decline.” Surgical oncology (2026). PMID: 42235333 ↗
L4COHORTCited in: Intraoperative Considerations and Complications - [102]
Madeka I, Noueihed K, Woodroof J et al.. “Lymph Node Dissection and Postoperative Complications After Lung Cancer Resection.” JAMA network open (2026). PMID: 42223938 ↗
L3RETROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [103]
Mugutso E, Freund O, Pitrou I et al.. “Blood eosinophil counts and postoperative outcomes in early-stage lung cancer: a retrospective cohort study.” Respiratory research (2026). PMID: 42067843 ↗
L3RETROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [104]
Huang L, Huang X, Zhou Y et al.. “Robotic-assisted versus video-assisted thoracoscopic anatomical pulmonary resection in elderly patients with lung cancer: A propensity score-matched comparison of short-term outcomes.” European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (2026). PMID: 42061191 ↗
L3COHORTCited in: Intraoperative Considerations and Complications - [105]
Petroncini M, Bertoglio P, Garelli E et al.. “Safe transition to robotics: How an established program on vats shapes postoperative outcomes in lung resection.” Journal of robotic surgery (2026). PMID: 41851556 ↗
L3COHORTCited in: Intraoperative Considerations and Complications - [106]
Seyoum N, Tohmasi S, Eaton DB et al.. “The impact of frailty on postoperative outcomes of veterans with stage I non-small cell lung cancer.” Surgery (2026). PMID: 41679123 ↗
L3RETROSPECTIVE_COHORTCited in: Intraoperative Considerations and Complications - [107]
Ferreira V, Minnella EM, Awasthi R et al.. “Multimodal Prehabilitation for Lung Cancer Surgery: A Randomized Controlled Trial.” The Annals of thoracic surgery (2020). PMID: 33321089 ↗
L1RCTCited in: Postoperative Recovery and ERAS - [108]
Tanaka F, Yokomise H, Soejima T et al.. “Induction Chemoradiotherapy (50 Gy), Followed by Resection, for Stage IIIA-N2 Non-Small Cell Lung Cancer.” The Annals of thoracic surgery (2018). PMID: 29890150 ↗
L2RCT_PHASE2Cited in: Postoperative Recovery and ERAS - [109]
Cascone T, Gold KA, Swisher SG et al.. “Induction Cisplatin Docetaxel Followed by Surgery and Erlotinib in Non-Small Cell Lung Cancer.” The Annals of thoracic surgery (2017). PMID: 29217088 ↗
L2RCT_PHASE2Cited in: Postoperative Recovery and ERAS - [110]
Salama M, Mueller MR. “Enhanced recovery in lung surgery: coaxial versus conventional chest drains following video-assisted thoracoscopic surgery lobectomy-a prospective randomized trial.” Journal of thoracic disease (2025). PMID: 41376917 ↗
L1RCTCited in: Postoperative Recovery and ERAS - [111]
Cui Z, Zhang Y, Xu C et al.. “Comparison of the results of two chest tube managements during an enhanced recovery program after video-assisted thoracoscopic lobectomy: A randomized trial.” Thoracic cancer (2019). PMID: 31475791 ↗
L1RCTCited in: Postoperative Recovery and ERAS - [112]
Huang FF, Yang Q, Zhang J et al.. “A self-efficacy enhancing intervention for pulmonary rehabilitation based on motivational interviewing for postoperative lung cancers patients: modeling and randomized exploratory trial.” Psychology, health & medicine (2018). PMID: 29384705 ↗
L1RCTCited in: Postoperative Recovery and ERAS - [113]
Driessen EJ, Peeters ME, Bongers BC et al.. “Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: A systematic review.” Critical reviews in oncology/hematology (2017). PMID: 28477748 ↗
L4SR_COHORTCited in: Postoperative Recovery and ERAS - [114]
Cavalheri V, Burtin C, Formico VR et al.. “Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer.” The Cochrane database of systematic reviews (2019). PMID: 31204439 ↗
L1SR_MA_RCTCited in: Postoperative Recovery and ERAS - [115]
Billiet C, Peeters S, Decaluwé H et al.. “Postoperative radiotherapy for lung cancer: Is it worth the controversy?” Cancer treatment reviews (2016). PMID: 27788387 ↗
L5NARRATIVE_REVIEWCited in: Postoperative Recovery and ERAS - [116]
Huang L, Kehlet H, Petersen RH. “Readmission after enhanced recovery video-assisted thoracoscopic surgery wedge resection.” Surgical endoscopy (2024). PMID: 38379006 ↗
L2PROSPECTIVE_COHORTCited in: Postoperative Recovery and ERAS - [117]
Wei W, Zhou J, Zhang Q et al.. “Postoperative intensity-modulated radiation therapy reduces local recurrence and improves overall survival in III-N2 non-small-cell lung cancer: A single-center, retrospective study.” Cancer medicine (2020). PMID: 32100444 ↗
L2NON_RANDOMIZED_TRIALCited in: Postoperative Recovery and ERAS - [118]
Huang J, Wang PL, Xiao JZ et al.. “Development and validation of a predictive model for acute postoperative pain after thoracoscopic lobectomy in patients with NSCLC: a multicenter retrospective study.” International journal of surgery (London, England) (2025). PMID: 41217365 ↗
L3RETROSPECTIVE_COHORTCited in: Postoperative Recovery and ERAS - [119]
Huang L, Frandsen MN, Kehlet H et al.. “Days alive and out of hospital after video-assisted thoracoscopic surgery wedge resection in the era of enhanced recovery.” BJS open (2023). PMID: 38108464 ↗
L4COHORTCited in: Postoperative Recovery and ERAS - [120]
Boyce-Fappiano D, Nguyen QN, Chapman BV et al.. “Single Institution Experience of Proton and Photon-based Postoperative Radiation Therapy for Non-small-cell Lung Cancer.” Clinical lung cancer (2021). PMID: 33707003 ↗
L3COHORTCited in: Postoperative Recovery and ERAS - [121]
Forster C, Doucet V, Perentes JY et al.. “Impact of an enhanced recovery after surgery pathway on thoracoscopic lobectomy outcomes in non-small cell lung cancer patients: a propensity score-matched study.” Translational lung cancer research (2021). PMID: 33569296 ↗
L3COHORTCited in: Postoperative Recovery and ERAS - [122]
Boonyawan K, Gomez DR, Komaki R et al.. “Clinical and Dosimetric Factors Predicting Grade ≥2 Radiation Pneumonitis After Postoperative Radiotherapy for Patients With Non-Small Cell Lung Carcinoma.” International journal of radiation oncology, biology, physics (2018). PMID: 29976504 ↗
L4COHORTCited in: Postoperative Recovery and ERAS - [123]
Hong TH, Cho JH, Shin S et al.. “Extended sleeve lobectomy for centrally located non-small-cell lung cancer: a 20-year single-centre experience.” European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (2018). PMID: 29408983 ↗
L4COHORTCited in: Postoperative Recovery and ERAS - [124]
Uda K, Matsui H, Fushimi K et al.. “Preoperative short-term plus postoperative physical therapy versus postoperative physical therapy alone for patients undergoing lung cancer surgery: retrospective analysis of a nationwide inpatient database.” European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (2018). PMID: 28950377 ↗
L3RETROSPECTIVE_COHORTCited in: Postoperative Recovery and ERAS - [125]
Song Y, Li C, Fang Y et al.. “Inflammatory cytokine profile in non-small cell lung Cancer (NSCLC) patients during early enhanced recovery after surgery (ERAS) period and its relation to hospital length of stay.” Cytokine (2025). PMID: 40120149 ↗
L3CASE_CONTROLCited in: Postoperative Recovery and ERAS - [126]
Zheng T, Zhang B, Zhang X et al.. “The safety and feasibility of non-intubated versus intubated video-assisted thoracic surgery in NSCLC patients after neoadjuvant therapy: a propensity score matching study.” Journal of thoracic disease (2026). PMID: 42182783 ↗
L4COHORTCited in: Postoperative Recovery and ERAS - [127]
Ettinger DS, Wood DE, Aisner DL et al.. “Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2022). PMID: 35545176 ↗
L1GUIDELINECited in: Outcomes by Stage and Approach - [128]
Ettinger DS, Aisner DL, Wood DE et al.. “NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.” Journal of the National Comprehensive Cancer Network : JNCCN (2018). PMID: 30006423 ↗
L1GUIDELINECited in: Outcomes by Stage and Approach - [129]
Ettinger DS, Wood DE, Aisner DL et al.. “Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National Comprehensive Cancer Network : JNCCN (2017). PMID: 28404761 ↗
L1GUIDELINECited in: Outcomes by Stage and Approach - [130]
Grossman SA, Ellsworth S, Campian J et al.. “Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors.” Journal of the National Comprehensive Cancer Network : JNCCN (2015). PMID: 26483062 ↗
L2SR_COHORTCited in: Outcomes by Stage and Approach - [131]
Chow R, Lage DE, Williams GR et al.. “Representation and Outcomes of Older Adults in Practice-Changing Oncology Trials in the Era of Novel Therapies: A Guideline Appraisal.” Journal of the National Comprehensive Cancer Network : JNCCN (2022). PMID: 34991068 ↗
L2SR_COHORTCited in: Outcomes by Stage and Approach - [132]
Vogelbaum MA, Brown PD, Messersmith H et al.. “Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021). PMID: 34932393 ↗
L1SR_MA_RCTCited in: Outcomes by Stage and Approach - [133]
Ahn MJ, Tanaka K, Paz-Ares L et al.. “Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024). PMID: 39250535 ↗
L1RCTCited in: Outcomes by Stage and Approach - [134]
Solomon BJ, Liu G, Felip E et al.. “Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024). PMID: 38819031 ↗
L1RCTCited in: Outcomes by Stage and Approach - [135]
Leighl NB, Akamatsu H, Lim SM et al.. “Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024). PMID: 38857463 ↗
L1RCTCited in: Outcomes by Stage and Approach - [136]
Reck M, Rodríguez-Abreu D, Robinson AG et al.. “Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021). PMID: 33872070 ↗
L1RCTCited in: Outcomes by Stage and Approach - [137]
Brahmer JR, Lee JS, Ciuleanu TE et al.. “Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022). PMID: 36223558 ↗
L1RCTCited in: Outcomes by Stage and Approach - [138]
Gadgeel S, Rodríguez-Abreu D, Speranza G et al.. “Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2020). PMID: 32150489 ↗
L1RCTCited in: Outcomes by Stage and Approach - [139]
Reck M, Rodríguez-Abreu D, Robinson AG et al.. “Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 30620668 ↗
L1RCTCited in: Outcomes by Stage and Approach - [140]
Waliany S, Roy SG, Pecci F et al.. “Efficacy and Safety of Continuing Next-Generation ALK TKIs With Chemotherapy for Advanced ALK-Positive NSCLC: A Multicenter Retrospective Study.” Journal of the National Comprehensive Cancer Network : JNCCN (2025). PMID: 41671458 ↗
L3RETROSPECTIVE_COHORTCited in: Outcomes by Stage and Approach - [141]
Bagley SJ, Talento S, Mitra N et al.. “Comparative Effectiveness of Carboplatin/Pemetrexed With Versus Without Bevacizumab for Advanced Nonsquamous Non-Small Cell Lung Cancer.” Journal of the National Comprehensive Cancer Network : JNCCN (2019). PMID: 31085759 ↗
L3RETROSPECTIVE_COHORTCited in: Outcomes by Stage and Approach - [142]
Hoffner B, Leighl NB, Davies M. “Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer.” Cancer treatment reviews (2020). PMID: 32078962 ↗
L1SR_MA_RCTCited in: Outcomes by Stage and Approach - [143]
Zhao Y, He Y, Wang W et al.. “Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis.” The Lancet. Oncology (2024). PMID: 39159630 ↗
L1SR_MA_RCTCited in: Outcomes by Stage and Approach - [144]
Conforti F, Pala L, Bagnardi V et al.. “Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis.” The Lancet. Oncology (2018). PMID: 29778737 ↗
L1SR_MA_RCTCited in: Outcomes by Stage and Approach - [145]
Wang J, Lu S, Yu X et al.. “Tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: final analysis of the randomized, phase III RATIONALE-307 trial.” ESMO open (2024). PMID: 39461775 ↗
L1RCTCited in: Outcomes by Stage and Approach - [146]
Carbone DP, Ciuleanu TE, Cobo M et al.. “Nivolumab plus ipilimumab with chemotherapy as first-line treatment of patients with metastatic non-small-cell lung cancer: final, 6-year outcomes from CheckMate 9LA.” ESMO open (2025). PMID: 40446626 ↗
L1RCTCited in: Outcomes by Stage and Approach