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Objectives: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes., Methods: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded., Results: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively ( P  < 0.001)., Conclusions: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC)., Background: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons., Methods: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes., Results: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS., Conclusions: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment., Competing Interests: All authors declare no conflicts of interest.

Background: Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen., Methods: A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease)., Results: Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis., Conclusions: Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Induction therapy is often recommended for patients with clinical stage IIIA-N2 (cIIIA/pN2) lung cancer. We examined whether postinduction positron emission tomography (PET) scans were associated with ypN2 disease and survival of patients with cIIIA/pN2 disease., Methods: We performed a retrospective review of a prospectively maintained database to identify patients with cIIIA/pN2 non-small cell lung cancer treated with induction chemotherapy followed by surgery between January 2007 and December 2012. The primary aim was the association between postinduction PET avidity and ypN2 status; the secondary aims were overall survival, disease-free survival, and recurrence., Results: Persistent pathologic N2 disease was present in 61% of patients (61 out of 100). PET N2-negative disease increased from 7% (6 out of 92) before induction therapy to 47% (36 out of 77) afterward. The sensitivity, specificity, and accuracy of postinduction PET for identification of ypN2 disease were 59%, 55%, and 57%, respectively. Logistic regression analysis indicated that postinduction PET N2 status was not associated with ypN2 disease. Of the 39 patients with both pre- and postinduction PET N2-avidity, 25 (64%) had ypN2 disease. The 5-year overall survival was 40% for ypN2 disease versus 38% for N2-persistent disease (P = .936); the 5-year overall survival was 43% for postinduction PET N2-negative disease versus 39% for N2-avid disease (P = .251). The 5-year disease-free survival was 34% for ypN2-negative disease versus 9% for N2-persistent disease (P = .079)., Conclusions: Postinduction PET avidity for N2 nodes is not associated with ypN2 disease, overall survival, or disease-free survival in patients undergoing induction chemotherapy for stage IIIA/pN2 disease., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Thoracic lymph nodes with marginally elevated maximum standardized uptake value (SUVmax) on PET/CT a diagnostic challenge in staging non-small-cell lung cancer. We evaluated the ratio of lymph node to primary tumor SUVmax (SUVN/T) in predicting nodal malignancy among 132 sampled nodes from 85 patients both a primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0. SUVN/T was more accurate than SUVmax for this subset of patients., Introduction/background: Among non-small-cell lung cancers with appreciable functional activity, positron emission tomography/computed tomography (PET/CT) is the most accurate imaging modality for clinical staging. However, lymph nodes (LN) with marginally elevated standardized uptake value (SUV) present a diagnostic challenge. In this retrospective study, we hypothesized that normalizing the LN SUV by using the ratio of the LN to primary tumor SUVmax (SUVN/T) may be a better predictor of nodal malignancy than using SUVmax alone for nodes with low to intermediate SUV., Patients and Methods: We identified 172 patients with newly diagnosed non-small-cell lung cancer who underwent pathologic LN staging and PET/CT within 31 days before biopsy. Receiver operating characteristic curves with area under the curve (AUC) calculations were used to evaluate SUVmax and SUVN/T for their ability to predict nodal malignancy for both the entire cohort of 504 LNs and a subset of 132 LNs from 85 patients who had both primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0., Results: In patients with primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0, SUVN/T was significantly more accurate in predicting nodal malignancy (AUC, 0.846; 95% confidence interval, 0.775-0.917) than SUVmax (AUC, 0.653; 95% confidence interval, 0.548-0.759). The optimal cutoff value of SUVN/T to predict nodal malignancy was 0.28 (90% sensitivity, 68% specificity). Sensitivity was > 95% for SUVN/T < 0.21, whereas specificity was > 95% for SUVN/T > 0.50., Conclusion: The ratio of LN SUV to primary tumor SUV on PET/CT is more accurate than SUVmax when assessing nodes of low to intermediate SUV., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Accurate assessment of lymph node (LN) involvement with malignancy is critical to staging and management of non-small-cell lung cancer. The goal of this retrospective study was to determine the tumor and imaging characteristics independently associated with malignant involvement of LNs visualized on positron emission tomography/computed tomography (PET/CT)., Methods: From 2002 to 2011, 172 patients with newly diagnosed non-small-cell lung cancer underwent PET/CT within 31 days before LN biopsy. Among these patients, 504 anatomically defined, pathology-confirmed LNs were visualized on PET/CT. Logistic regression analysis was used to determine the associations between nodal involvement with malignancy and several clinical and imaging variables, including tumor histology, tumor grade, LN risk category in relation to the primary tumor location, pathologic findings from additional biopsied LNs, interval between PET/CT and biopsy, primary tumor largest dimension, primary tumor standardized uptake value (SUVmax), LN short-axis dimension, and LN SUVmax., Results: On univariate analysis, adenocarcinoma histology (p = 0.010), high LN risk category (p < 0.001), larger LN short-axis dimension (p < 0.001), and higher LN SUVmax (p < 0.001) all correlated with nodal involvement. On multivariate analysis, adenocarcinoma histology (p = 0.003), high LN risk category (p = 0.005), and higher LN SUVmax (p < 0.001) correlated with nodal involvement, whereas LN short-axis dimension was no longer statistically significant (p = 0.180). A nomogram developed for clinical application based on this analysis had excellent concordance between predicted and observed results (concordance index, 0.95)., Conclusion: Adenocarcinoma histology, higher LN SUVmax, and higher LN risk category independently correlate with nodal involvement with malignancy and may be used in a model to accurately predict the risk of a node's involvement with malignancy.

Introduction: Guidance is limited for invasive staging in patients with lung cancer without mediastinal disease by positron emission tomography (PET). We developed and validated a prediction model for pathologic N2 disease (pN2), using six previously described risk factors: tumor location and size by computed tomography (CT), nodal disease by CT, maximum standardized uptake value of the primary tumor, N1 by PET, and histology., Methods: A cohort study (2004-2009) was performed in patients with T1/T2 by CT and N0/N1 by PET. Logistic regression analysis was used to develop a prediction model for pN2 among a random development set (n = 625). The model was validated in both the development set, which comprised two thirds of the patients and the validation set (n = 313), which comprised the remaining one third. Model performance was assessed in terms of discrimination and calibration., Results: Among 938 patients, 9.9% had pN2 (9 detected by invasive staging and 84 intraoperatively). In the development set, univariate analyses demonstrated a significant association between pN2 and increasing tumor size (p < 0.001), nodal status by CT (p = 0.007), maximum standardized uptake value of the primary tumor (p = 0.027), and N1 by PET (p < 0.001); however, only N1 by PET was associated with pN2 (p < 0.001) in the multivariate prediction model. The model performed reasonably well in the development (c-statistic, 0.70; 95% confidence interval, 0.63-0.77; goodness of fit p = 0.61) and validation (c-statistic, 0.65; 95% confidence interval, 0.56-0.74; goodness-of-fit p = 0.19) sets., Conclusion: A prediction model for pN2 based on six previously described risk factors has reasonable performance characteristics. Observations from this study may guide prospective, multicenter development and validation of a prediction model for pN2.

Objective: We previously reported a high mortality after induction therapy and pneumonectomy for non-small cell lung cancer. Recent reports suggest that operative mortality in these patients is declining. We analyzed our contemporary results to define operative mortality and factors determining surgical risk., Methods: Eligible patients were identified from our prospective surgical database. Complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Uni- and multivariate logistic regression models assessed the association of preoperative tests and clinical characteristics with outcome. Receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) statistics were calculated in a leave-one-out crossvalidation scheme to evaluate the predictive value of various models., Results: From January 2000 to December 2006, 549 patients underwent surgery after induction therapy. Median patient age was 64 years (range: 30-86), and 54% were women (298/549). All received chemotherapy, and 17% also had radiation. Lobectomy (388/549, 71%) and pneumonectomy (70/549, 13%) were the most common procedures. Complications occurred in 250 patients (46%), with grade 3 or higher in 23% (126/549). Inhospital mortality was 1.8% (10/549), with only one death after right pneumonectomy (1/30, 3%). Multivariate analysis showed that predicted postoperative (PPO) pulmonary function was associated with postoperative morbidity. By receiver operating characteristic curves, PPO product (AUC = 0.75, p < 0.001), PPO diffusion capacity (AUC = 0.70, p < 0.001), and preoperative % predicted PPO diffusion capacity (AUC = 0.66, p < 0.001) predicted mortality., Conclusion: Our current experience shows that resection of non-small cell lung cancer after induction therapy, including pneumonectomy, is associated with low mortality. PPO pulmonary function is the strongest predictor of operative risk and should be used to select patients for surgery.

Background: The optimal surgical technique for lobectomy in lung cancer is not well defined. Proponents of video-assisted thoracic surgery (VATS) hypothesize that less trauma leads to quicker recovery, whereas those who advocate thoracotomy claim it as an oncologically superior procedure. However, a well-balanced comparison of the two procedures is lacking in the literature., Methods: All patients who underwent lobectomy for clinical stage 1A lung cancer by computed tomographic and positron emission tomographic scan were identified from a prospective database. Patient characteristics were compared by the Student t test, Pearson chi(2), and Fisher exact test. A propensity score-matched analysis was performed. Survival was assessed by Kaplan-Meier and Cox proportional hazards analysis. Complications were assessed by a multivariate logistic regression model evaluating age, sex, comorbidities, pulmonary function, tumor size, nodal status, surgeon, and histologic characteristics., Results: From May 2002 to August 2007, 398 patients underwent an attempt at VATS lobectomy and 343 underwent thoracotomy. An "intent-to-treat" analysis was performed. There was 1 postoperative death in each group. Survival by Cox model was no different for VATS versus thoracotomy (hazard ratio 0.72; P = .12), whereas age (hazard ratio 1.03; P < .001), larger tumor size (hazard ratio 1.34; P < .001), and higher nodal stage (hazard ratio 1.92; P < .001) were associated with worse survival. Logistic regression demonstrated fewer complications for VATS lobectomy (odds ratio 0.73; P = .06), whereas age (odds ratio 1.04; P < .001) and tumor size (odds ratio 1.2; P < .020) correlated with a greater number of complications. Patients undergoing VATS lobectomy demonstrated a 2-day shorter length of stay than patients undergoing thoracotomy (P < .001). Propensity score-matched analysis supported these findings., Conclusions: VATS lobectomy and thoracotomy demonstrated similar 5-year survivals. However, VATS lobectomy was associated with fewer complications and shorter length of hospital stay.