Lobe-specific Nodal Dissection Research Articles

Long-term survival outcomes after lobe-specific nodal dissection in patients with early non-small-cell lung cancer.

We investigated the long-term outcomes of lobe-specific nodal dissection (LSD) and systematic nodal dissection (SND) in patients with non-small-cell lung cancer (NSCLC). Patients with c-stage I and II NSCLC who underwent lobectomy with mediastinal nodal dissection were retrospectively analysed. After propensity score matching, we assessed the overall survival (OS), recurrence-free survival (RFS) and cumulative incidence of death (CID) from primary lung cancer and other diseases. The median follow-up period was 8.4 years. Among 438 propensity score-matched pairs, OS and RFS were similar between the LSD and SND groups [hazard ratio (HR), 0.979; 95% confidence interval (CI), 0.799-1.199; and HR, 0.912; 95% CI, 0.762-1.092, respectively], but the LSD group showed a better prognosis after 5 years postoperatively. CID from primary lung cancer was similar between the 2 groups (HR, 1.239; 95% CI, 0.940-1.633). However, the CID from other diseases was lower in the LSD group than in the SND group (HR, 0.702; 95% CI, 0.525-0.938). According to c-stage, the LSD group tended towards worse OS and RFS, with higher CID from primary lung cancer than the SND group, in patients with c-stage II. LSD provides acceptable long-term survival for patients with early-stage NSCLC. However, LSD may not be suitable for patients with c-stage II NSCLC due to the higher mortality risk from primary lung cancer.

Lobe-specific nodal dissection with intraoperative frozen section analysis for clinical stage-I non-small cell lung cancer: a validation study by propensity score matching.

Lobe-specific nodal dissection (LND) is increasingly used for non-small cell lung cancer (NSCLC) in Japan; however, its treatment validity remains unclarified. Since 2013, LND has been used as a standard procedure for clinical stage-I (c-stage-I) NSCLC at our institution. We aimed to evaluate its validity using intraoperative frozen section analysis (FSA) for c-stage-I NSCLC. The participants comprised patients with NSCLC who underwent LND between 2013 and 2016 (n = 307) or systematic nodal dissection (SND) between 2002 and 2013 (n = 367) for c-stage-I disease. FSA was routinely performed in LND to examine at least three stations. Outcomes were compared between the LND and SND groups. Patients in whom LND was converted to SND due to metastasis on FSA of the sampled lymph node were still categorized into the LND group, i.e., intention-to-treat analysis. The prognostic impact was compared using propensity score matching. The rate of conversion from LND to SND was 10.4%. Of the patients converted to SND, 12.5% had metastases outside the LND area. False-negative N2 results were detected in only 0.7% of the LND group patients after FSA. After matching, each group had 220 patients. There were no significant between-group differences in the lymph-node recurrence rate (7% vs. 6%), 5-year recurrence-free survival (80.1% vs. 79.0%), and overall survival (90.4% vs. 90.3%). LND with intraoperative FSA is a valid modality that could serve as a standard surgical procedure for c-stage-I NSCLC. Intraoperative FSA may lower the residual lymph-node metastasis risk in LND.

Permissible Outcomes of Lobe-Specific Lymph Node Dissection for Elevated Carcinoembryonic Antigen in Non-Small Cell Lung Cancer.

Background and Objectives: Lobe-specific nodal dissection (L-SND) is currently acceptable for the dissection of early-stage non-small cell lung cancer (NSCLC) but not for cancers of more advanced clinical stages. We aimed to assess the efficacy of L-SND, compared to systemic nodal dissection (SND). Materials and Methods: We retrospectively collected the clinical data of patients with carcinoembryonic antigen (CEA) abnormality who underwent complete resection of NSCLC via lobectomy or more in addition to either SND or L-SND at two cancer-specific institutions from January 2006 to December 2017. Results: A total of 799 patients, including 265 patients who underwent SND and 534 patients who underwent L-SND, were included. On multivariate analysis, thoracotomy, more than lobectomy, cN1-2, advanced pathological stage, adjuvant treatment, and EGFR or ALK were strongly associated with SND. No significant differences were found in overall survival, disease-free survival, and overtime survival after propensity adjustment (p = 0.09, p = 0.11, and p = 0.50, respectively). There were no significant differences in local (p = 0.16), regional (p = 0.72), or distant (p = 0.39) tumor recurrence between the two groups. Conclusions: SND did not improve the prognosis of NSCLC patients with CEA abnormality. Complete pulmonary resection via L-SND seems useful for NSCLC patients with CEA abnormality.

The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer.

Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobe-specific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for R0, R(un) (p< 0.0001), and R1 (p < 0.001), respectively, with no significant difference between R0 and R(un) in pN0 cases. R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies.

P2.17-09 Preoperative Risk Factors of Potential Failure for Lobe-Specific Nodal Dissection in Clinical Early Stage (I-IIA) Non-Small Cell Lung Cancer

Clinical early stage (I-IIA) non-small cell lung cancer (NSCLC) is treated with pulmonary resection and systematic nodal dissection (SND) or lobe-specific nodal dissection. The aim of this study was to identify the preoperative risk factors for potential failure of lobe-specific nodal dissection in clinical early stage NSCLC. A retrospective review was carried out on patients who underwent pulmonary lobectomy and SND for clinical early stage (I-IIA) NSCLC. Patients with computed tomography and positron emission tomography were included, whereas patients with invasive mediastinal staging and right middle lobe tumor were excluded. Lobe-specific nodal dissection failure was defined as unexpected metastasis at inferior mediastinal nodes (stations 7, 8, and 9) for both upper lobe tumors and at superior mediastinal nodes (stations 2R and 4R for right upper lobe tumors and stations 4L, 5 and 6 for left upper lobe tumors) for both lower lobe tumors. The incidence of pN2 disease following the tumor location and the factors for the failure of lobe-specific nodal dissection were analyzed. From July 2005 to May 2017, 2130 patients were included in this study. Overall, 12.5% (266/2130) of the patients had pN2 disease. Among them, 33.2% (78/266) of pN2 patients showed potential failure of lobe-specific nodal dissection. Lobe-specific nodal dissection failure was shown in 49 of 764 (6.4%), 21 of 468 (4.5%), 2 of 534 (0.4%), and 6 of 364 (1.6%) cases in right upper lobe, right lower lobe, left upper lobe and left lower lobe, respectively. At multivariable analysis, female (OR: 1.86; 95% CI 1.14-3.03; p = 0.012), right upper lobe tumor (OR: 20.98; 95% CI 5.05-87.08; p <0.001), right lower lobe tumor (OR:14.81; CI 3.43-63.97; p <0.001), higher SUVmax (≥4.75) (OR: 5.51; 95% CI 3.18-9.55; p <0.001), and adenocarcinoma histology (OR: 8.89; 95% CI 2.11-37.42; p = 0.003) were significant risk factors for the failure of lobe-specific nodal dissection Lobe specific nodal dissection revealed a considerable failure rate in clinical early stage NSCLC. Lobe-specific SND should be performed cautiously in clinical early stage NSCLC, especially in patients with female sex, right sided tumor, higher SUVmax (≥4.75) and adenocarcinoma histology.

MA23.11 Lobe-Specific Nodal Dissection for Clinical Stage I and II Non-Small Cell Lung Cancer: Japanese Multi-Institutional Retrospective Study

MA23.11 Lobe-Specific Nodal Dissection for Clinical Stage I and II Non-Small Cell Lung Cancer: Japanese Multi-Institutional Retrospective Study

Lobe-Specific Nodal Dissection for Clinical Stage I and II NSCLC: Japanese Multi-Institutional Retrospective Study Using a Propensity Score Analysis

ObjectivesThe purpose of this study was to assess the surgical outcomes according to the extent of mediastinal lymph node dissection for patients with NSCLC by using a nationwide registry database. MethodsFrom among 11,663 patients in a Japanese lung cancer registry study for 2004, 5392 patients with clinical stage (c-stage) I or II NSCLC that was completely resected by lobectomy and either systematic (SND) or lobe-specific nodal dissection (LSD) were enrolled. Patients who received preoperative therapy or had middle lobe tumor were excluded. In the LSD group, inferior mediastinal (subcarinal) nodes were not dissected for upper lobe tumors, and superior mediastinal nodes were not dissected for lower lobe tumors. To reduce the selection bias, an inverse probability of treatment weighting method using a propensity score was implemented. ResultsLSD and SND were performed in 1268 patients (23.5%) and 4124 patients (76.5%), respectively. The LSD group included more upper lobe and c-stage I tumors and less pathological N2 disease than the SND group. Extended pathological N2 disease outside LSD area was found in 3.2% of the SND group. The 5-year overall survival was 81.5% in the LSD group and 75.9% in the SND group. An inverse probability of treatment weighting–adjusted Cox model showed that LSD did not have a negative prognostic impact and instead was associated with favorable survival (hazard ratio = 0.68, 95% confidence interval: 0.60−0.77). ConclusionsThis retrospective registry study suggested that LSD is an alternative to SND for selected patients with c-stage I or II NSCLC. Future prospective studies are warranted to determine whether LSD is applicable and provides clinical benefit for the general population of patients with c-stage I or II NSCLC.

Lymphadenectomy for clinical early-stage non-small-cell lung cancer: a systematic review and meta-analysis.

The benefits of different methods of lymphadenectomy for early-stage non-small-cell lung cancer (NSCLC) remain controversial. Herein, we performed a systematic review and meta-analysis comparing survival benefits of systematic nodal dissection (SND) with those of lymph nodal sampling (LNS) and lobe-specific nodal dissection (L-SND). PubMed, OVID, EBSCO and Springer were searched up to August 2015 for English language studies. Data of selected studies were extracted. Study quality, publication bias and heterogeneity were assessed. Analysis was performed using a random-effects model. A total of 12 studies were identified [4 randomized prospective clinical trials (RCTs) and 8 observational trials] that reported surgical outcomes of 3955 patients with resectable clinical N2 negative NSCLC: 2142 underwent SND and 1813 underwent LNS/L-SND. In the cohort studies, the SND group had a statistically significant improvement in overall survival (OS) [hazard ratios (HRs), 1.24; 95% confidence interval (CI) 1.02-1.5] and recurrence-free survival (RFS) rates (HR, 1.27; 95% CI 1.03-1.58). The pooled HR from RCTs showed a consistent tendency in terms of OS (HR = 1.13, 95% CI 0.94-1.35) and RFS (HR = 0.99, 95% CI 0.82-1.19), in spite of a non-significant difference. In subgroup analyses, the SND group had a statistically significant improvement in OS (HR, 1.40; 95% CI 1.12-1.76) and RFS (HR, 1.5; 95% CI 1.09-2.08) in cohort studies, and a consistent tendency of OS in RCTs (HR = 1.12, 95% CI 0.93-1.35) with non-significant difference. However, there was no significant difference in OS (HR, 1.02; 95% CI 0.66-1.57) and RFS (HR, 1.11; 95% CI 0.87-1.42) between the SND and L-SND group. In early-stage NSCLC patients, LNS was associated with inferior survival rates, while L-SND seemed to provide equal survival benefits compared with SND, and the indications need to be identified.

Action point: intraoperative lymph node staging

When performing a lung cancer resection in patients who are technically and functionally operable, complete resection remains a major prognostic factor. Although still a controversial topic, specific criteria have been published to precisely define a complete resection [1]. These include that a systematic nodal dissection has been performed or at least, a lobe-specific nodal dissection. In both instances removal of at least six lymph node stations is required, of which three have to be in the mediastinum. Also, the highest mediastinal lymph node should be negative on definitive pathological examination. The European Society of Thoracic Surgeons (ESTS) published guidelines for preoperative and intraoperative lymph node staging in order to guide surgeons in performing a thorough lymph node evaluation [2, 3]. In almost all recent papers on lung cancer resection, the authors mention that these specific guidelines were carefully followed. In the present manuscript, the completeness of mediastinal nodal dissection was evaluated in four major hospitals in the Netherlands, three community and one university hospital [4]. All surgeons had a specific certification in thoracic surgery. The results are surprising: in only 36% of the patients at least three mediastinal lymph node stations were removed. Even more disturbing was the fact that a complete lymph node dissection according to the ESTS guidelines was performed in only 4% of patients. No difference was found between cardiothoracic and general surgeons with an additional certification in thoracic surgery. This clearly implies that many patients were understaged and that even the pathological tumour–node–metastasis (TNM) classification cannot be considered to be accurate. Although this is a retrospective cohort analysis in a relatively small number of patients, this study demonstrates that we do not live in an ideal world and that in daily practice guidelines are not adequately followed. This seems to be a generalized problem and similar figures were reported in other studies. This not only relates to intraoperative nodal dissection but also to invasive staging and in a specific study lymph node biopsies were taken in <50% of patients undergoing mediastinoscopy [5]. The main question is why even dedicated thoracic surgeons are so reluctant to perform a thorough mediastinal lymph node dissection. Admittedly, operative time is somewhat increased and there is a risk of intraoperative bleeding from major structures as the azygos vein or superior vena cava, and a higher risk of chylous leakage from cut mediastinal lymphatic vessels. The subcarinal zone is more difficult to reach, especially when performing a video-assisted thoracic surgical (VATS) procedure. Do thoracic surgeons rely on integrated computed tomographicpositron emission tomographic (CT-PET) scanning or the recently introduced minimally invasive techniques as endoscopic and endobronchial ultrasound? Is formal lymph node dissection not necessary anymore when you have performed a mediastinoscopy preoperatively, although not all mediastinal lymph node stations are within reach of the mediastinoscope and the false negative rate is 10%? Financial issues may also be involved and recently, in Belgium reimbursement has been increased when a systematic nodal dissection is performed during lung cancer resection. The recently published American College of Surgery Oncology Group (ACOSOG) Z0030 phase III trial showing no difference in survival in patients with clinical T1-2, non-hilar N1 non-small cell lung cancer who were randomized between lymph node sampling and systematic nodal dissection, is misinterpreted by many surgeons and oncologists [6]. It should be stressed that these patients had a thorough pathologic evaluation of four nodal stations, of which three had to be in the mediastinum, before they were randomized. This is certainly not current practice in many thoracic centres and so, the results of the ACOSOG trial cannot be generalized. The main message of the present study is that further education and training of thoracic surgeons, residents and fellows is necessary to increase the accuracy of intraoperative lymph node staging. Major thoracic surgical associations have the obligation to address this topic in their annual programme, educational and postgraduate sessions. Hopefully, the new nodal map introducing the concept of nodal zones grouping several lymph node stations, will increase the awareness of the importance of nodal staging and improve the overall quality of our surgical practice [7].