Lymphovascular Invasion is an Independent Negative Prognostic Factor in Esophageal Adenocarcinoma.

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.

The Relationship Between Nodal Metastases and Primary Location in Stage I Non-Small Cell Lung Cancer.

INTRODUCTION: This study examines the relationship between location of the primary tumor and specific nodal metastases in clinical stage 1 non-small cell lung cancer (NSCLC) patients undergoing lobectomy. METHODS: We retrospectively analyzed all lobectomies performed at a single institution, between January 2005 and December 2019, for clinical stage I NSCLC patients. Patients selected for this study were clinically node negative (cN0) by positron emission tomography-computed tomography scan and selectively by endobronchial ultrasound or mediastinoscopy. Cases of postoperative pathologic nodal upstaging were identified among these patients. For each patient upstaged, the specific lymph node stations found to be positive were recorded. Descriptive statistics, chi-squared tests, and Fisher's exact test were utilized to identify independent risk factors for upstaging to specific N1 and N2 lymph node stations. All clinical and pathologic staging information was retrospectively normalized to the International Association for the Study of Lung Cancer 8th Edition TNM Classification. RESULTS: The research cohort included 645 patients. The mean age was 68 years (standard deviation ± 9.2), 54% were female, and 88% were White, 11% Black, and 1% other. Twelve percent (n = 75) were upstaged from cN0 to pN1 or pN2 upon final pathologic examination: 41 to pN1 (54.7%) and 34 to pN2 (45.3%). The primary tumor location with the highest rate of nodal upstaging was the left upper lobe (LUL) (12.8%). Tumors in the right middle lobe had the lowest rate of unsuspected nodal metastases (8.8%). Out of all upstaged patients, there were no positive level eight lymph nodes, and only 1 patient with a positive level nine lymph node. Lymph node levels five and six were only positive in LUL primary tumors, a relationship that approached statistical significance (P = 0.0797). No patients with a LUL primary tumor had a positive level seven lymph node. Upstaging at station 12 was significantly associated with the location of the primary tumor, occurring less often in tumors originating in the right upper lobe in comparison to other lobes (P = 0.0288). CONCLUSIONS: We identified relationships between the location of a primary tumor and specific nodal upstaging in patients with clinical stage I NSCLC who undergo lobectomy. We found the following: 1) only 1 patient had a positive level eight or nine lymph node out of 645 patients; 2) only LUL primary tumors demonstrated upstaging to level five or six lymph nodes; and 3) right upper lobe tumors were significantly less likely to be associated with a positive level 12 lymph node.

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.

Nodal upstaging evaluation in NSCLC patients treated by robotic lobectomy.

BACKGROUND: Open pulmonary resection is considered the gold standard treatment of early-stage non-small cell lung cancer (NSCLC). However, in the last decades, the use of minimal-invasive techniques has given promising results. Survival in lung cancer, after surgery, depends on the number of pathological nodes (pN), thus lymph nodal upstaging can be considered a surrogate for surgical quality of the procedure. Several studies have demonstrated a lower rate of upstaging in video-assisted thoracic surgery than in open surgery, suggesting an approach-related difference in lymphadenectomy. Features of robotic technique could consent a lymph nodal dissection similar to open surgery. The aim of the study is to compare nodal upstaging between thoracotomy and robotic approaches to evaluate the oncologic radicality. METHODS: Between January 2013 and December 2016, 212 consecutive cN0 NSCLC patients underwent lobectomy and lymphadenectomy (N1 + N2 stations) by either thoracotomy (Open Group) or robotic surgery (Robotic Group). RESULTS: Lobectomy and lymphadenectomy were performed in 106 cN0-cN1 NSCLC patients by robotic surgery and in 106 cN0-cN1 NSCLC patients by open surgery. A mean of 14.42 ± 6.99 lymph nodes was removed in the Robotic Group (RG) and a mean of 14.32 ± 7.34 nodes in the Open Group (OG). Nodal upstaging was observed in 22 (20.75%) RG patients and in 19 OG (17.92%) patients. CONCLUSIONS: Robotic lobectomy for clinical N0-N1 NSCLC appears to be equivalent to thoracotomy in terms of efficacy of lymph node dissection and nodal upstaging. Given that the nodal upstaging is a surrogate of quality of surgery, we can consider robotic lobectomy an appropriate procedure which ensures similar result to the open approach.

A standardized technique of systematic mediastinal lymph node dissection by video-assisted thoracoscopic surgery (VATS) leads to a high rate of nodal upstaging in early-stage non-small cell lung cancer.

BACKGROUND: A substantial part of the oncologic surgical procedure in non-small cell lung cancer (NSCLC) is systematic lymph node dissection (sLND). However, controversies still exist regarding the quality of minimally invasive (video-assisted thoracoscopic surgery, VATS) sLND in oncologic resections. The rate of stage migration from clinical to pathological N-status has been discussed as one parameter for the quality of sLND. METHODS: Between March 2011 and May 2014, seventy-seven patients (62 male, 15 female) were scheduled for anatomical lung resection and sLND by VATS for clinical stage I (UICC 7th edition) NSCLC. Preoperative staging was performed by [18F]-fluorodesoxyglucose positron emission tomography with computed tomography (FDG-PET/CT). Patient data were retrospectively analyzed with regard to divergence in clinical and pathological N-factor. FDG-PET/CTs of patients with lymph node (LN) upstaging after VATS resections were blindly re-evaluated by an experienced radiologist. RESULTS: In FDG-PET/CT, preoperative tumor stage was cT1N0M0 in 41 (53.2%) and cT2aN0M0 in 28 (36.4%) patients. In six (7.8%) patients the primary tumor was not suspicious for malignancy, and in two (2.6%) patients the tumor was not evaluable due to prior wedge resection before FDG-PET/CT. Thirty-one (40.3%) left-sided and 46 (59.7%) right-sided pulmonary resections with sLND were performed; 19.57 ± 0.99 LNs were dissected. In 13 (16.9%) patients a nodal stage migration from preoperative clinical to postoperative pathological N-stage was observed [cN0 to pN1 in 9 (11.7%) and cN0 to pN2 in 4 (5.2%) cases]. In correlation to the clinical T-factor, the rate of N-factor upstaging for cT1 was 12.2% and for cT2a was 28.6%, respectively. In 50% of the patients with postoperative nodal staging shift, no changes were observed on re-evaluation of the preoperative FDG-PET/CT. CONCLUSION: In this series of clinical stage I NSCLC patients, the rate of nodal stage migration after sLND by VATS is higher than previously reported. Prospective randomized controlled trials are needed to prove the oncologic quality of a sLND by VATS versus standard open approach.

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.

Quality of lymph node dissection and early recurrence in robotic versus thoracoscopic lobectomy for stage N1-2 non-small cell lung cancer: Eleven-year real-world data from a high-volume center.

BACKGROUND: The efficacy of lymph node dissection (LND) and oncological outcomes of robot-assisted (RL) versus video-assisted thoracoscopic lobectomy (VL) for non-small cell lung cancer (NSCLC) with nodal involvement remains controversial. This study aims to compare LND quality and early recurrence (ER) rate between RL and VL for stage N1-2 NSCLC patients based on eleven-year real-world data from a high-volume center. METHODS: Pathologic stage IIB-IIIB (T1-3N1-2) NSCLC patients undergoing RL or VL in Shanghai Chest Hospital from 2010 to 2021 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM, 1:4 RL versus VL) was performed to mitigate baseline differences. LND quality was evaluated by adequate (≥16) LND and nodal upstaging rates. ER was defined as recurrence occurring within 24 months post-surgery. RESULTS: Out of 1578 cases reviewed, PSM yielded 200 RL and 800 VL cases. Without compromising perioperative outcomes, RL assessed more N1 and N2 LNs and N1 stations, and led to higher incidences of adequate LND (58.5 % vs. 42.0 %, p < 0.001) and nodal upstaging (p = 0.026), compared to VL. Notably, RL improved perioperative outcomes for patients undergoing adequate LND than VL. Finally, RL notably reduced ER rate (22.0 % vs. 29.6 %, p = 0.032), especially LN ER rate (15.0 % vs. 21.5 %, p = 0.041), and prolonged disease-free survival (DFS; hazard ratio = 0.837, p = 0.040) compared with VL. Further subgroup analysis of ER and DFS within the cN1-2-stage cohort verified this survival benefit. CONCLUSIONS: RL surpasses VL in enhancing LND quality, reducing ER rates, and improving perioperative outcomes when adequate LND is performed for stage N1-2 NSCLC patients.

Preoperative PET-SUVmax and volume based PET parameters of the primary tumor fail to predict nodal upstaging in early-stage lung cancer.

OBJECTIVES: Accurate nodal staging is of utmost importance in patients with lung cancer. FDG-PET/CT imaging is now part of the routine staging. Despite thorough preoperative staging nodal upstaging still occurs in early-stage lung cancer. However, the predictive value of preoperative PET metrics of the primary tumor on nodal upstaging remains to be unexplored. Our aim was to assess the association of these preoperative PET-parameters with nodal upstaging in histologically confirmed lung adenocarcinoma and squamous cell carcinoma. METHODS: From January 2016 to November 2018, 500 patients with pT1-T2/cN0 lung cancer received an anatomical resection with curative intent. 171 patients with adenocarcinoma and squamous cell carcinoma and available PET-CTs were retrospectively included. We analyzed the the association of nodal upstaging with preoperative PET-SUVmax and metabolic PET metrics including total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with different defined thresholds. RESULTS: High values of preoperative PET-SUVmax of the primary tumor were associated with squamous cell carcinoma (p < 0.0001) and with larger tumors (p < 0.0001). Increased preoperative C-reactive protein levels (<1mg/dL) correlated significantly with high preoperative PET-SUVmax values (p < 0.0001). No significant relationship between PET-SUVmax and lactate dehydrogenase activity (p = 0.6818), white blood cell count (p = 0.7681), gender (p = 0.1115) or age (p = 0.9284) was observed. Nodal upstaging rate was 14.0 % with 8.8 % N1 and 5.3 % N2 upstaging. Tumor size (p = 0.0468) and number of removed lymph nodes (p = 0.0461) were significant predictors of nodal upstaging but no significant association was found with histology or PET parameters. Of note, increased MTV - regardless of the threshold - tended to associate with nodal upstaging. CONCLUSION: Early-stage lung cancer patients with squamous histology and T2 tumors presented increased preoperative PET-SUVmax values. Nevertheless, beyond tumor size and number of removed lymph nodes neither SUVmax nor metabolic PET parameters MTV and TLG were significant predictors of nodal upstaging.

Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database.

Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the "Italian VATS-Group" database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan-Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44-2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11-2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96-0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30-0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15-3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01-1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging.

Different nodal upstaging rates and prognoses for patients with clinical T1N0M0 lung adenocarcinoma classified according to the presence of solid components in the lung and mediastinal windows.

Background: Little is known about the correlation between nodal upstaging and pulmonary nodules classified according to the presence of solid components in the lung and mediastinal windows. This study thus aimed to analyze the risk factors of nodal upstaging and prognosis based on different imaging features, clinical characteristics, and pathological results from patients with clinical stage T1N0M0 lung adenocarcinoma. Methods: A total of 340 patients between January 2016 and June 2017 were selected from the Affiliated Hospital of Qingdao University database. Imaging features, clinical characteristics, and pathological results were collected for survival and analysis of nodal upstaging risk factors. We used logistic regression models to identify important metastatic risk factors for nodal upstaging. Survival rates were calculated using Kaplan-Meier (KM) survival curves and compared with the log-rank test. Significant prognostic risk factors were identified using the Cox proportional hazards model. Results: A total of 340 patients, with an average age of 64.89 (±8.775) years, were enrolled. Among them, nonnodal upstaging occurred both in 77 (22.6%) patients with pure ground-glass nodules (pGGNs) and in 30 (8.8%) patients with heterogenous ground-glass nodules (hGGNs). Compared to the 92 (27.1%) patients with real part-solid nodules (rPSNs), the 141 (41.5%) patients with solid nodules were significantly different in terms of in nodal upstaging (P<0.001). Moreover, preoperative carcinoembryonic antigen (CEA) level >3.4 µg/L [odds ratio (OR): 2.931; 95% confidence interval (CI): 1.511-5.688; P=0.001], imaging tumor size >18.3 mm (OR, 3.482; 95% CI: 1.609-7.535; P=0.002), and consolidation tumor ratio (CTR) >0.788 (OR 8.791; 95% CI: 3.570-21.651; P<0.001) were independent risk factors for nodal upstaging. The KM survival curve results showed that patients with pGGNs and those with hGGNs had a much better 5-year disease-free survival (DFS) and 5-year overall survival (OS) than did those with rPSNs and those with solid nodules (DFS: 98.7% vs. 100% vs. 81.4% vs. 73.7%, P<0.001; OS: 97.4% vs. 100% vs. 90.2% vs. 83.7%, P=0.003). In the multivariate Cox regression analysis of patients with rPSNs and solid nodules, tumor location and pathological lymph node grade were found to be independent risk factors for DFS and OS. Conclusions: Patients with pGGNs and those with hGGNs were more likely to be free of nodal upstaging and had better prognosis than did those with clinical stage IA rPSNs and solid nodules. The patients with pGGNs or hGGNs with preoperative CEA level <3.4 µg/L, imaging tumor size <18.3 mm, and CTR <0.788 can choose systematic lymph node sampling (SLNS) or decline lymph node dissection to avoid postoperative complications.

Results of video-assisted thoracoscopic surgery versus thoracotomy for lung cancer in a mixed practice medium-volume hospital: a propensity-matched study.

OBJECTIVES: The aim of this study was to compare the short- and long-term results of video-assisted thoracoscopic surgery (VATS) and thoracotomy for non-small-cell lung cancer in a medium-volume centre, where cardiothoracic surgeons perform both cardiac and general thoracic surgery. The primary outcome of interest was 5-year overall survival and disease-specific survival. Secondary outcomes were short-term postoperative complications, length of hospital stay and lymph node yield. METHODS: This was a retrospective cohort study including 670 lung cancer patients undergoing VATS (n = 207) or open surgery (n = 463) with a curative intent in Oulu University Hospital between the years 2000-2020. Propensity score matching was implemented with surgical technique as the dependent and age, sex, Charlson comorbidity index, pulmonary function, pathological stage, histological type and the year of the operation as covariates resulting in 127 pairs. RESULTS: In the propensity-matched cohort, 5-year overall survival was 64.3% after VATS and 63.2% after thoracotomy (P = 0.969). Five-year disease-specific survival was 71.6% vs 76.2% (P = 0.559). There were no differences in overall (34.6% vs 44.9%, p = 0.096) or major postoperative complications (8.7% vs 14.2%, P = 0.167) between the study groups. The average length of hospital stay was shorter (5.8 vs 6.6 days, P = 0.012) and the median lymph node yield was lower (4.0 vs 7.0, P < 0.001) in the VATS group compared to the thoracotomy group. CONCLUSIONS: According to this study, the long-term results of lung cancer surgery in a mixed practice are comparable between VATS and open surgery.

Oncological Outcomes of Robotic Lobectomy and Radical Lymphadenectomy for Early-Stage Non-Small Cell Lung Cancer.

Background: While the thoracotomy approach was considered the gold standard until two decades ago, robotic surgery has increasingly strengthened its role in lung cancer treatment, improving patients' peri-operative outcomes. In this study, we report our experience in robotic lobectomy for early-stage non-small cell lung cancer, with particular attention to oncological outcomes and nodal upstaging rate. Methods: We retrospectively reviewed patients who underwent lobectomy and radical lymphadenectomy at our Institute between 2016 and 2020. We selected 299 patients who met the inclusion criteria of the study. We analyzed the demographic features of the groups as well as their nodal upstaging rate after pathological examination. Then, we analyzed disease-free and overall survival of the entire enrolled patient population and we compared the same oncological outcomes in the upstaging and the non-upstaging group. Results: A total of 299 patients who underwent robotic lobectomy were enrolled. After surgery, 55 patients reported nodal hilar or mediastinal upstaging. The 3-year overall survival of the entire population was 82.8%. The upstaging group and the non-upstaging group were homogeneous for age, gender, smoking habits, clinical stage, tumor site, tumor histology. The non-upstaging group had better OS (p = 0.004) and DFS (p < 0.0001). Conclusion: Our results show that robotic surgery is a safe and feasible approach for the treatment of early-stage NSCLC, especially for its accuracy in mediastinal lymphadenectomy. The oncological outcomes were encouraging and consistent with previous findings.

Surgical Effectiveness of Uniportal-VATS Lobectomy Compared to Open Surgery in Early-Stage Lung Cancer.

Background: Although the feasibility and safety of Uniportal-Video-Assisted thoracic surgery (U-VATS) has been proven, its surgical effectiveness is still debated. The aim of this study is to assess the equivalence of the U-VATS approach compared with an open technique in terms of surgical (nodal-upstaging, complications, and post-operative results) and short-term survival outcomes. Methods: The clinical data of patients undergoing lobectomy for NSCLC at our center, from January 2014 to December 2019, were analyzed retrospectively. All patients undergoing open or U-VATS lobectomy with lymphadenectomy for early-stage lung cancer (cT1-T3N0, stages IA-IIB) were included in the study. Only 230 patients satisfied the inclusion criteria. Group bias was reduced through 1:1 propensity score matching, which resulted in 46 patients in each group (open surgery and U-VATS). Results: The intra- and post-operative mortality were null in both groups. There was no difference in the post-operative complications (p: 1.00) between U-VATS and open lobectomy. There was also no recorded difference in the pathological nodal up-staging [11 (23.9%) after thoracotomy vs. 8 (17.4%) after U-VATS, p: 0.440). The chest tube duration was longer in the open group (p: 0.025), with a higher post-operative pain (p: 0.001). Additionally, the 3-year overall survival (OS) was 78% after U-VATS lobectomy vs. 74% after open lobectomy (p: 0.204), while 3-year disease-specific survival (DSS) was 97 vs. 89% (p: 0.371), respectively. The 3-year disease-free survival (DFS) was 62% in the U-VATS group and 66% in the thoracotomy group, respectively (p: 0.917). Conclusions: Uniportal-VATS lobectomy for the treatment of early-stage lung cancer seems to be a safe and effective technique with similar surgical and short-term survival outcomes as open surgery, but with lower post-operative pain and shorter in-hospital stay.

Sublobar resection without staging and lymphadenectomy for ≤2 cm Non-Small Cell Lung Cancer is no adequate therapy.

OBJECTIVE: Sublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with ≤2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors ≤2 cm at our institution. METHODS: Nodal upstaging, lymphangiosis- (L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method. RESULTS: 747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with ≤2 cm tumors. The mean tumor size was 1.4 cm ± 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 ± 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 ± 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p < 0.001). Upstaged patients showed significantly worse 3- (upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates. CONCLUSION: 16.5% of patients with ≤2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Factors Associated with Nodal Upstaging in Clinical T1a-bN0M0 Non-Small Cell Lung Cancers.

Nodal upstaging of lung adenocarcinoma occurs when unexpected pathological lymph node metastasis is found after surgical intervention, and may be associated with a worse prognosis. In this study, we aimed to determine the predictive factors of nodal upstaging in cT1a-bN0M0 primary lung adenocarcinoma. We retrospectively reviewed a prospective database (January 2011 to May 2017) at National Taiwan University Hospital and identified patients with cT1a-bN0M0 (solid part tumor diameter ≤ 2 cm) lung adenocarcinoma who underwent video-assisted thoracoscopic lobectomy. Logistic regression models and survival analysis were used to examine and compare the predictive factors of nodal upstaging. A total of 352 patients were included. Among them, 28 (7.8%) patients had nodal upstaging. Abnormal preoperative serum carcinoembryonic antigen (CEA) levels, solid part tumor diameter ≥ 1.3 cm, and consolidation-tumor (C/T) ratio ≥ 0.50 on chest computed tomography (CT) were significant predictive factors associated with nodal upstaging, and patients with nodal upstaging tended to have worse survival. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.

Outcomes of nodal upstaging comparing video-assisted thoracoscopic surgery versus open thoracotomy for lung cancer.

OBJECTIVES: In early stage non-small cell lung cancer, the optimal surgical approach for lymph node dissection remains controversial. Without a uniform standard for the quality of lymph node dissection, outcomes of nodal upstaging comparing video-assisted thoracoscopic surgery (VATS) versus open thoracotomy (OPEN) also remain controversial. Thus, we compared the clinical outcomes of nodal upstaging between each approach. MATERIALS AND METHODS: We retrospectively evaluated 1319 surgically resected lung cancer cases between 2008 and 2017 at our institute. Moreover, 348 VATS and 348 OPEN cases were extracted using propensity score matching. We investigated the frequency, prognosis, and post-recurrence course of nodal upstaging between each approach. RESULTS: A total of 193 nodal upstaging cases were identified. Nodal upstaging was more frequent in the OPEN group (24 %) than the VATS group (9%) (p < 0.001). However, multivariable analysis revealed the surgical approach was not significantly associated with nodal upstaging (OPEN: odds ratio, 1.3; 95 % confidence interval, 0.93-2.02; p = 0.108) and, after matching, nodal upstaging with each approach were of equivalent frequency (p = 0.752). The median follow-up period was 5.0 years. Nodal upstaging was an independent prognostic factor for worse overall survival, cancer-specific survival, and recurrence-free survival in multivariable analyses (all p < 0.001). Of all cases, 222 recurred after surgery. There were no significant differences in recurrence patterns and initial recurrence sites depending on surgical approach. The 5-year post-recurrence survival rate was 52 % after VATS and 30 % after OPEN; however, this difference was not statistically significant (p = 0.052). Moreover, post-recurrence survival rate was not significantly different between the VATS and OPEN groups (pN0: p = 0.268, pN1: p = 0.437, and pN2: p = 0.144). CONCLUSION: Outcomes of nodal upstaging between VATS and OPEN were found to be equivalent. The difference in the frequency of nodal upstaging was not due to inferior quality of lymph node dissection with VATS; rather, that difference resulted from selection bias.

Comparison between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery for mediastinal and hilar lymph node dissection in lung cancer surgery.

OBJECTIVES: Lymph node dissection (LND) with robot-assisted thoracoscopic surgery (RATS) in lung cancer surgery has not been fully evaluated. The aim of this study was to compare LND surgical results between video-assisted thoracoscopic surgery (VATS) and RATS. METHODS: We retrospectively compared perioperative parameters, including the incidence of LND-associated complications (chylothorax, recurrent and/or phrenic nerve paralysis and bronchopleural fistula), lymph node (LN) counts and postoperative locoregional recurrence, among 390 patients with primary lung cancer who underwent lobectomy and mediastinal LND by RATS (n = 104) or VATS (n = 286) at our institution. RESULTS: The median total dissected LN numbers significantly differed between the RATS and the VATS groups (RATS: 18, VATS: 15; P < 0.001). They also significantly differed in right upper zone and hilar (#2R + #4R + #10L) (RATS: 12, VATS: 10; P = 0.002), left lower paratracheal and hilar (#4L + #10L) (RATS: 4, VATS: 3; P = 0.019), aortopulmonary zone (#5 + #6) (RATS: 3, VATS: 2; P = 0.001) and interlobar and lobar (#11 + #12) LNs (RATS: 7, VATS: 6; P = 0.041). The groups did not significantly differ in overall nodal upstaging (P = 0.64), total blood loss (P = 0.69) or incidence of LND-associated complications (P = 0.77). CONCLUSIONS: In this comparison, it was suggested that more LNs could be dissected using RATS than VATS, especially in bilateral superior mediastinum and hilar regions. Accumulation of more cases and longer observation periods are needed to verify whether RATS can provide the acceptable quality of LND and local control of lung cancer.

Nodal Outcomes of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery for Clinical Stage I Lung Cancer.

BACKGROUND: Accurate intraoperative assessment of mediastinal lymph nodes is a critical aspect of lung cancer surgery. The efficacy and potential for upstaging implicit in these dissections must therefore be revisited in the current era of uniportal video-assisted thoracoscopic surgery (VATS). METHODS: A retrospective study was conducted in which 544 patients with stage I (T1abc-T2a, N0, M0) primary lung cancer were analyzed. To assess risk factors for nodal upstaging and to limit any imbalance imposed by surgical choices, we constructed an inverse probability of treatment-weighted (IPTW) logistic regression model (in addition to non-weighted logistic models). We also evaluated risk factors for early locoregional recurrence using IPTW logistic regression analysis. RESULTS: In the comparison of uniportal and multiportal VATS, the resected lymph node count (14.03±8.02 vs. 14.41±7.41, respectively; p=0.48) and rate of nodal upstaging (6.5% vs. 8.7%, respectively; p=0.51) appeared similar. Predictors of nodal upstaging included tumor size (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.12-2.70), carcinoembryonic antigen level (OR, 1.11; 95% CI, 1.04-1.18), and histologically confirmed pleural invasion (OR, 3.97; 95% CI, 1.89-8.34). The risk factors for locoregional recurrence within 1 year were found to be number of resected N2 nodes, age, and nodal upstaging. CONCLUSION: Uniportal and multiportal VATS appear similar with regard to accuracy and thoroughness, showing no significant difference in the extent of nodal dissection.

Prognosis of upstaged N1 and N2 disease after curative resection in patients with clinical N0 non-small cell lung cancer.

BACKGROUND: Nodal upstaging occasionally occurs after curative resection in clinical N0 non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the prognosis of clinical N0 NSCLC (T1-2, tumor size 5 cm or smaller) after upstaging to pathologic N1 or N2. METHODS: From 2005 to 2015, 676 consecutive patients were diagnosed with clinical T1-2N0 NSCLC and underwent curative resection. Among these, tumors were upstaged to N1 in 46 patients and to N2 in 24 patients. We analyzed the prognosis of upstaged tumors. For comparison of prognosis between nodal upstaging groups and others in the same stage, patients with preoperative pathologically proven N1 (n=31) and N2 (n=55) NSCLC were included in the study. RESULTS: A total of 70 patients (10.4%) had nodal upstaging after curative resection of clinical N0 NSCLC. Upstaging to N1 occurred in 46 patients and upstaging to N2 occurred in 24 patients. The 5-year disease-specific survival rate was not statistically different between the upstaged and non-upstaged N1/N2 groups in N1 disease (73.3% vs. 70.5%, P=0.247) or in N2 disease (58.9% vs. 50.7%, P=0.283). Multivariate analysis showed that nodal upstaging was not a significant prognostic factor in N1 or N2 NSCLC (hazard ratio =0.385, P=0.235; hazard ratio =0.677, P=0.458). CONCLUSIONS: Postoperative nodal upstaging from clinical T1-2N0 NSCLC was not a significant prognostic factor in the same stage. Therefore, surgical treatment of clinical T1-2N0 lung cancer diagnosed by imaging without preoperative pathologic lymph node staging can be a treatment option.

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

Abstract 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.