The American Cancer Society National Lung Cancer Roundtable strategic plan: Promoting guideline-concordant lung cancer staging.

Accurate staging improves lung cancer survival by increasing the chances of delivering stage-appropriate therapy. However, there is underutilization of, and variability in, the use of guideline-recommended diagnostic tests used to stage lung cancer. Consequently, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) convened the Triage for Appropriate Treatment Task Group-a multidisciplinary expert and stakeholder panel-to identify knowledge and/or resource gaps contributing to guideline-discordant staging and make recommendations to overcome these gaps. The task group determined the following: Gap 1: facilitators of and barriers to guideline-concordant staging are incompletely understood; Recommendation 1: identify facilitators of and barriers to guideline-concordant lung cancer staging; Gap 2: the level of evidence supporting staging algorithms is low-to-moderate; Recommendation 2: prioritize comparative-effectiveness studies evaluating lung cancer staging; Gap 3: guideline recommendations vary across professional societies; Recommendation 3: harmonize guideline recommendations across professional societies; Gap 4: existing databases do not contain sufficient information to measure guideline-concordant staging; Recommendation 4: augment existing databases with the information required to measure guideline-concordant staging; Gap 5: health systems do not have a performance feedback mechanism for lung cancer staging; Recommendation 5: develop and implement a performance feedback mechanism for lung cancer staging; Gap 6: patients rarely self-advocate for guideline-concordant staging; Recommendation 6: increase opportunities for patient self-advocacy for guideline-concordant staging; and Gap 7: current health policies do not motivate guideline-concordant lung cancer staging; Recommendation 7: organize a representative working group under the ACS NLCRT that promotes policies that motivate guideline-concordant lung cancer staging. PLAIN LANGUAGE SUMMARY: Staging-determining the degree of cancer spread-is important because it helps clinicians choose the best cancer treatment. Receiving the best cancer treatment leads to the best possible patient outcomes. Practice guidelines are intended to help clinicians stage patients with lung cancer. However, lung cancer staging in the United States often varies from practice guideline recommendations. This report identifies seven opportunities to improve lung cancer staging.

An International Survey of Mediastinal Staging Practices amongst Interventional Bronchoscopists.

INTRODUCTION: In potentially curable non-small-cell lung cancer, different practice guidelines recommend invasive me-diastinal staging in tumors larger than 3 cm, central, or hy-permetabolic N1 lymph nodes. There is no consensus concerning the use of an endosonographic procedure or a mediastinoscopy in the first line in patients with a radiologically normal mediastinum, while in case of a mediastinal involvement, the latest European guidelines recommend the combination of endobronchial ultrasound (EBUS) and endoscopic ultrasound/endoscopic ultrasound with EBUS endoscope (EUS/EUS-B), using a systematic endosonographic procedure. This international survey was conducted to describe current medical practices in endoscopic mediastinal staging amongst interventional bronchoscopists. METHODS: A survey was developed and sent to all members of different interventional pulmonology societies, with the purpose to describe who, when and how an endoscopic mediastinal staging was performed. RESULTS: One hundred and fifty-three bronchoscopists responded to the survey. Most of them practiced in Europe (n = 84, 55%) and North America (n = 52, 34%). In the first line, EBUS alone was the most widely used endoscopic procedure for mediastinal staging. Half of the responders performed a systematic endoscopic staging procedure, including a systematic examination of all accessible nodal stations and a sampling of all lymph nodes >5 mm in the short axis at each station. A higher proportion of bronchoscopists who have completed a dedicated fellowship program performed systematic endoscopic mediastinal staging. Few endoscopists routinely perform combined EBUS/EUS(-B) for mediastinal staging and use the combination only in selected cases. CONCLUSION: There are several areas of divergence between published guidelines and current practices reported by interventional bronchoscopists. EBUS alone is the most widely used endoscopic procedure for mediastinal staging in lung cancer, and a combined endoscopic approach is frequently omitted by the responders. A fellowship program appears to be associated with a higher rate of systematic endoscopic staging procedures.

Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry.

PURPOSE: Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors. METHODS: From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status. RESULTS: Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and > 12 resected nodes were independent predictors of nodal upstaging. CONCLUSIONS: The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

The Role of Endobronchial Ultrasound in Early-Stage Non-Small Cell Lung Cancer.

Aim The aim of this study is to assess the impact of EBUS on the concordance of clinical and pathological NSCLC staging in our center. Methods Data was collected retrospectively from the hospital database regarding patients who underwent surgical resection for early stage NSCLC between 2012 and 2017. Results A total of 251 patients were included. The mean age was 67 (±9), 55% (n=137) were male and 83% (n=209) were current/former smokers. In group A (n=154, 61%) clinical nodal stage (cN) was established from a combination of CT, PET CT and mediastinoscopy. Group B underwent additional EBUS (n=97, 39%). cN and pathological nodal staging (pN) were concordant in 78% (n=120) in group A versus 62% (n=60) in group B (p=0.009). Conclusion This study demonstrated higher rates of nodal discordance in patients who underwent EBUS which contrasts existing data that demonstrates improved concordance with EBUS. We describe these findings and potential explanations further in this study.

PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114).

BACKGROUND: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial.

BACKGROUND: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy. METHODS/DESIGN: This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates 'bulky N2-N3' disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment. DISCUSSION: Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register on July 6th, 2017 ( NTR 6528 ).

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Staging of Patients with Non-Small Cell Lung Cancer without Mediastinal Involvement at Positron Emission Tomography-Computed Tomography.

BACKGROUND: Staging of lung cancer is essential to the treatment, which is curative only in cases of localized disease. Previous studies have suggested that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is unnecessary when positron emission tomography-computed tomography (PET-CT) shows no mediastinal involvement. OBJECTIVE: The aim of the study was to investigate how often EBUS-TBNA resulted in a clinically relevant upstaging in patients with lung cancer without mediastinal involvement at PET-CT. METHODS: A total of 981 consecutive patients from 2009 to 2014 were referred for preoperative EBUS-TBNA. We included 167 patients with lung cancer without involvement of the mediastinum at PET-CT (115 N0 and 52 N1). RESULTS: Of the 167 patients included, 10 (6.0%) were upstaged to N2 or N3 by EBUS-TBNA; 9 of these were originally classified as N1 at PET-CT. Therefore, 17.3% of the included N1 patients were upstaged to N2/N3 after EBUS-TBNA. This compares to only 0.9% of the N0 patients. After both EBUS-TBNA and PET-CT, 115 patients were operated, and 12 (10.4%) of these proved to be N2/N3. We calculated the sensitivity as 42.9%, the specificity as 99.0%, and the negative predictive value as 89.6%. CONCLUSIONS: The overall probability of a clinically relevant upstaging by EBUS-TBNA in patients judged as N0/N1 at PET-CT was 6.0%, compared to 0.9% in patients classified as N0 and 17.3% in patients classified as N1. The risk of overlooking N2/N3 disease after both PET-CT and EBUS-TBNA was 10.4%.

Surgical Treatment of Lung Cancer.

In this chapter, we discuss the preoperative evaluation that is necessary prior to surgical resection, stage-specific surgical management of lung cancer, and the procedural steps as well as the indications to a variety of surgical approaches to lung resection.

Using pet-ct to reduce futile thoracotomy rates in non-small-cell lung cancer: a population-based review.

BACKGROUND: Combined positron-emission tomography and computed tomography (pet-ct) reduces futile thoracotomy (ft) rates in patients with non-small-cell lung cancer (nsclc). We sought to identify preoperative risk factors for ft in patients staged with pet-ct. METHODS: We retrospectively reviewed all patients referred to the BC Cancer Agency during 2009-2010 who underwent pet-ct and thoracotomy for nsclc. Patients with clinical N2 disease were excluded. An ft was defined as any of a benign lesion; an exploratory thoracotomy; pathologic N2 or N3, stage iiib or iv, or inoperable T3 or T4 disease; and recurrence or death within 1 year of surgery. RESULTS: Of the 108 patients who met the inclusion criteria, ft occurred in 27. The main reason for ft was recurrence within 1 year (14 patients) and pathologic N2 disease (10 patients). On multivariate analysis, an Eastern Cooperative Oncology Group performance status greater than 1, a pet-ct positive N1 status, a primary tumour larger than 3 cm, and a period of more than 16 weeks from pet-ct to surgery were associated with ft. N2 disease that had been negative on pet-ct occurred in 21% of patients with a pet-ct positive N1 status and in 20% of patients with tumours larger than 3 cm and non-biopsy mediastinal staging only. The combination of pet-ct positive N1 status and a primary larger than 3 cm had 85% specificity, and the presence of either risk factor had 100% sensitivity, for ft attributable to N2 disease. CONCLUSIONS: To reduce ft attributable to N2 disease, tissue biopsy for mediastinal staging should be considered for patients with pet-ct positive N1 status and with tumours larger than 3 cm even with a pet-ct negative mediastinum.

When to Consider Invasive Lymph Node Staging in Non-Small-Cell Lung Cancer? A Novel Scoring System Utilising Metabolic Parameters in 18F-FDG PET/CT.

OBJECTIVE: The maximum standardised uptake value (SUVmax) is a widely utilised metric in positron emission tomography/computed tomography for clinically staging non-small-cell lung cancer (NSCLC), yet the reliability of SUVmax remains controversial. We herein aimed to assess the effectiveness of semi-quantitative parameters, encompassing size, SUVmax, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and heterogeneity factor (HF), in evaluating both primary tumours and lymph nodes (LNs) on positron emission tomography/computed tomography. A novel scoring system was devised to appraise the role of semi-quantitative parameters and visually evaluate LNs for nodal staging. MATERIALS AND METHODS: Patients with pathological NSCLC, diagnosed between 2014 and 2019 and clinically staged I-III, were enrolled in the study. Patient demographics, including age, sex, tumour location, diameter, tumour-node-metastasis stage, as well as SUVmax, MTV, TLG and HF parameters of primary tumours and LNs, were documented. RESULTS: The analysis comprised 319 patients and 963 LNs. Patients had a mean age of 61.62 years, with 91.5% being male. Adenocarcinoma exhibited a histological association with LN metastasis (P=0.043). The study findings revealed that tumour size, SUVmax, MTV, TLG and HF did not significantly affect the detection of LN metastasis. Conversely, non-squamous cell carcinoma, LNs exhibiting higher FDG levels than the liver, LN size, SUVmax, MTV and TLG were identified as risk factors (P<0.0001). The identified cut-off values were 1.05cm for LN size, 4.055 for SUVmax, 1.805cm3 for MTV and 5.485 for TLG. The scoring system incorporated these parameters, and visual assessment indicated that a score of ≥3 increased the risk of metastasis by 14.33 times. CONCLUSION: We devised a novel scoring system and demonstrated that LNs with a score of ≥3 in patients with NSCLC have a high likelihood of metastasis. This innovative scoring system can serve as a valuable tool to mitigate excessive and extreme measures in the assessment of invasive pathological staging.

Surgical access to the mediastinum-all roads lead to Rome: a literature review.

Background and Objective: The mediastinum is a complex, heterogeneous area, which leads vertically across the thoracic cavity between the bilateral mediastinal pleurae, connecting the head and neck region with the thoracic cavity. Different classifications have been published to differentiate between the so-called mediastinal compartments while the most used classification surely is the 4-compartments Gray`s classification, dividing it into the superior, anterior, middle and posterior mediastinum. Mediastinal abnormalities include infections (mediastinitis) and solid or cystic mediastinal masses. These masses can be divided into benign and malignant lesions originating from mediastinal structures/organs or represent manifestations of metastatic disease, often metastatic non-small cell lung cancer (NSCLC). This review aims to explore the different mediastinal pathologies along with indications and surgical approaches. Methods: We performed literature research in PubMed, MEDLINE, Embase, CENTRAL, and CINAHL databases. Only papers written in English were included. Key Content and Findings: Depending on the indication for surgical intervention and the localization of the pathology, surgical approach may differ immensely. Mediastinal staging of lung cancer, primary lesions of the mediastinum, mediastinitis and traumatic mediastinal injuries display the most frequent indications for mediastinal surgery. Surgical approaches trend towards minimally invasive, video- or robotic-assisted techniques and are becoming increasingly refined to adapt to the special characteristics of the mediastinum. However, certain indications still require open access for best possible mediastinal exposure or oncological reasons. Conclusions: To guide optimal surgical approach selection to the mediastinum, the following overview will present all published surgical approaches to the mediastinum and discuss their practical relevance and indications aiming to help surgeons in the management of patients with mediastinal pathologies who should undergo surgery.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery.

Background: Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2. Methods: Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression. Results: A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs. 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors. Conclusions: Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging.

Improved Accuracy and Sensitivity in Diagnosis and Staging of Lung Cancer with Systematic and Combined Endobronchial and Endoscopic Ultrasound (EBUS-EUS): Experience from a Tertiary Center.

BACKGROUND: Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances. METHODS: Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed. RESULTS: A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure (p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure (p < 0.001). CONCLUSION: The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone.

[Changes in mediastinal lymph node sampling practices]. / Évolution des pratiques concernant l'exploration ganglionnaire médiastinale.

INTRODUCTION: While mediastinoscopy is considered the gold standard for mediastinal node sampling, it is to some extent being superseded by endobronchial ultrasound. The objective of this study was to evaluate the different practices in our center regarding mediastinal lymph node sampling in lung cancer patients. METHODS: Data were collected from patients having undergone mediastinal lymph node sampling by video-assisted-mediastinoscopy (VM) or by endobronchial ultrasound (EBUS) in our center between August 2020 and July 2023. The modalities of the two procedures and their diagnostic accuracy were analyzed, as was their evolution over time. RESULTS: The 362 patients comprised 217 who were sampled by EBUS and 145 by VM. Overall, the procedures became more frequent, with EBUS tending to supersede VM. The number of harvested lymph nodes gradually grew, and less unforeseen lymph node invasion and upstaging occurred. CONCLUSION: The arrival in our center of endobronchial ultrasound yielded an overall increase of lymph node sampling despite a decrease in the number of mediastinoscopy procedures performed. Reinforced compliance with guidelines is needed to improve the diagnostic accuracy of these techniques and to better ensure quality of care.

Endobronchial ultrasound-transbronchial needle aspiration: effectiveness and accuracy in non-small cell lung cancer staging.

INTRODUCTION: Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) has a cardinal role in the diagnosis and staging of non-small cell lung cancer (NSCLC), providing an accurate nodal staging in a less invasive way than surgical biopsy. The aim of this study was to assess the diagnostic accuracy of EBUS-TBNA in the pre-operative NSCLC mediastinal staging, as well as to evaluate EBUS-TBNA specificity and sensibility in our cohort. METHODS: We retrospectively analyzed data of NSCLC patients who underwent EBUS-TBNA followed by major pulmonary resection between January 2020 and December 2022. EBUS-TBNA was performed in patients with NSCLC (central T ≤ 3 cm, peripheral/central T > 3 cm), following the ESTS guidelines. The target nodes were selected on the basis of their radiologic/metabolic characteristics. Each procedure was conducted together with rapid on-site cytological evaluation (ROSE). RESULTS: Twenty-five patients were included (M/F = 17/8). At least three needle passages on each target lymph node were performed. No complications during or after the procedures occurred. We found a 100% correspondence between ROSE on the sampled nodes and postoperative pathologic findings. An upstaging occurred in three cases (12%) because of the involvement of stations 5 and 6 (not accessible via EBUS), while the only case of downstaging (N2 → N0, 4%) was probably due to intercurrent neoadjuvant chemotherapy. In all cases, EBUS-TBNA has proved to achieve a diagnostic procedure on the target nodes. CONCLUSIONS: EBUS-TBNA is a safe and effective procedure that offers high sensitivity and specificity when performed together with ROSE, which improves the accuracy of sampling. Doubt on nodal stations 5 and 6 involvement should be settled by other techniques.

The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC.

BACKGROUND: Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller. METHODS: We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence. RESULTS: There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group. CONCLUSIONS: The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.

Endobronchial Ultrasound/Transbronchial Needle Aspiration-Biopsy for Systematic Mediastinal lymph Node Staging of Non-Small Cell Lung Cancer in Patients Eligible for Surgery: A Prospective Multicenter Study.

BACKGROUND: The treatment of lung cancer depends on histological and/or cytological evaluation of the mediastinal lymph nodes. Endobronchial ultrasound/transbronchial needle aspiration-biopsy (EBUS/TBNA-TBNB) is the only minimally invasive technique for a diagnostic exploration of the mediastinum. The aim of this study is to analyze the reliability of EBUS in the preoperative staging of non-small cell lung cancer (NSCLC). METHODS: A prospective study was conducted from December 2019 to December 2022 on 217 NSCLC patients, who underwent preoperative mediastinal staging using EBUS/TBNA-TBNB according to the ACCP and ESTS guidelines. The following variables were analyzed in order to define the performance of the endoscopic technique-comparing the final staging of lung cancer after pulmonary resection with the operative histological findings: clinical characteristics, lymph nodes examined, number of samples, and likelihood ratio for positive and negative outcomes. RESULTS: No morbidity or mortality was noted. All patients were discharged from hospital on day one. In 201 patients (92.6%), the preoperative staging using EBUS and the definitive staging deriving from the evaluation of the operative specimen after lung resection were the same; the same number of patients were detected in downstaging and upstaging (8 and 8, 7.4%). The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 90%, 90%, 82%, 94%, and 90%, respectively. The likelihood ratio for positive and negative results was 9 and 0.9, respectively, confirming cancer when present and excluding it when absent. CONCLUSIONS: EBUS is the only low-invasive and easy procedure for mediastinal staging. The possibility to check the method in each of its phases-through direct visualization of the vessels regardless of their location in relation to the lymph nodes-makes it safe both for the endoscopist and for the patient. Certainly, the cytologist/histologist and/or operator must have adequate expertise in order not to negatively affect the outcome of the method, although three procedures appear to reduce the impact of the individual professional involved on performance.

Accuracy of nodal staging by 18F-FDG-PET/CT in limited disease small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is highly aggressive with a nearly incurable disease in most cases. The most important prognostic factor is the status of the mediastinal lymph nodes. Only a small proportion of patients can be diagnosed at early stages and directed to curative multimodal treatment. Therefore, accuracy of nodal staging by (18F)-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (18F-FDG-PET/CT) in (very) limited disease SCLC, although not well investigated, is highly important. METHODS: Treatment naive, non-bulky patients treated or diagnosed with SCLC between June 2012 and April 2020 with complete data including FDG-PET/CT and invasive mediastinal staging were retrospectively analyzed (n = 19). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of mediastinal lymph node staging of 18F-FDG-PET/CT was calculated. RESULTS: The FDG-PET/CT showed a sensitivity of 91%, and the specificity was calculated as 87.5%. In this cohort, the disease prevalence in lymph nodes was 58% (n = 11). Positive predictive value was 91%, NPV 88% and accuracy calculated at 89%. One patient was upstaged from single-level N2 to multilevel N2. In one patient, upstaging in invasive staging was performed from N2 to N3, and one patient was downstaged from N1 to N0. CONCLUSIONS: FDG-PET/CT is a valuable tool for the detection of distant metastases, but in mediastinal staging of SCLC some limitations might remain. Invasive methods remain the gold standard. Therefore, the mediastinal lymph nodal status of patients with SCLC screened for multimodal treatment should be further evaluated by additional invasive techniques to verify the exact N-staging and to optimize treatment stratification.

Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? STUDY DESIGN AND METHODS: For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021). RESULTS: The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration. INTERPRETATION: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02991924; URL: www. CLINICALTRIALS: gov.

Preoperative mediastinal staging in early-stage lung cancer: Targeted nodal sampling is not inferior to systematic nodal sampling.

OBJECTIVE: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05. RESULTS: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. CONCLUSIONS: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients.