Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma

Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n=150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n=209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P=0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P=0.37). The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.

Surgical Assessment and Intraoperative Management of Mediastinal Lymph Nodes in Non-Small Cell Lung Cancer

The optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated. We reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2-3 N0-1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs. Cancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node "in the systematic LND field" that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%). Systematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.

Supplement 2, Proceedings of the 14th World Conference on Lung Cancer, Book 2

Is Lymph Node Dissection Required in Pulmonary Metastasectomy for Colorectal Adenocarcinoma?

Invited Commentary

Segment Location and Ground Glass Opacity Ratio Reliably Predict Node-Negative Status in Lung Cancer

Mediastinal Nodal Involvement in Patients with Clinical Stage I Non–Small-Cell Lung Cancer: Possibility of Rational Lymph Node Dissection

Reply to the Editor

Segmentectomy and mediastinal lymph node dissection (MLND) are becoming standard procedures for small-sized (<2 cm) peripheral non-small cell lung cancer (NSCLC). Although the benefits of the less resected lung are proven, the extent of lymph node dissection remains unchanged. We studied 422 patients who underwent lobectomy with MLND (lobe specific or systemic) for small peripheral NSCLC with clinical N0 disease. Patients with middle lobectomy (n = 39) and a consolidation-to-tumor (C/T) ratio ≤0.50 (n = 33) were excluded. We investigated the clinical factors, lymph node metastasis distributions, and lymph node recurrence patterns of 350 patients. Thirty-five (10.0%) patients had lymph node metastasis; none with C/T ratio <0.75 had lymph node metastasis and lymph node recurrence. None had solitary lymph node metastasis in the outside lobe-specific MLND. Six patients had mediastinal lymph node metastasis at the initial site of recurrence; none had mediastinal lymph node recurrence outside the lobe-specific MLND, except for two patients with S6 primary disease. NSCLC patients with small peripheral tumors and a C/T ratio <0.75 during segmentectomy may not require MLND. The optimal MLND for patients with a C/T ratio ≥0.75, except for those with S6 primary, may be lobe-specific MLND.

Indication and extent of lymph node dissection in differentiated thyroid carcinoma are still subject to controversy. The overall favourable prognosis, low study numbers and the different biological features of papillary and follicular carcinoma lead to few evidence-based recommendations and a low level of evidence. The different therapeutic and operative strategies are illustrated on the principles of evidence-based medicine. A literature search was carried out in Medline and EMBase using the keywords differentiated/papillary/follicular thyroid carcinoma, lymphadenectomy, lymph node dissection. PTC: Eleven retrospective studies outline the effect of prophylactic vs. no lymph node dissection on tumour relapse rate and long-term survival. Six of these studies combine PTC and FTC. A minor evidence-based recommendation for prophylactic cervico-central lymph node dissection in PTC can be given (evidence level 3). Lymph node dissections involving the cervico-lateral compartment can be recommended in the case of clinically pathological findings at the lymph nodes (evidence level 3). A prophylactic mediastinal lymph node dissection is not indicated (evidence level 4), a therapeutic mediastinal LAD cannot be recommended because of higher morbidity and mortality (evidence level 3). FTC: 3 retrospective studies outline the effect of prophylactic lymph node dissection on tumour relapse rate and long-term survival. Based on these, a recommendation for prophylactic cervico-central systematic lymph node dissection can be given for invasive follicular carcinoma (evidence level 3). There is no indication for prophylactic cervico-lateral or mediastinal lymph node dissection (evidence level 3). The following recommendations can be given in differentiated thyroid carcinoma: In the case of clinically pathological findings in cervical lymph nodes, a systematic lymph node dissection of the lateral and central compartment is indicated (evidence level 3). Prophylactic cervico-central lymph node dissection is recommended for PTC larger than 10 mm in diameter and invasive FTC, a cervico-lateral or mediastinal prophylactic lymph node dissection is not indicated (evidence level 3). In papillary microcarcinoma and minimally invasive follicular carcinoma, a prophylactic lymph node dissection is not indicated (evidence level 3).

With recent advances in radiology, the detection of ground-glass nodules (GGNs) has become increasingly common. However, there still is no consensus on management, especially on the need for systemic lymph node (LN) dissection. The purpose of this study was to evaluate the surgical outcomes on the basis of the extent of resection of the primary lesion and mediastinal LN dissection and to carefully suggest appropriate treatment strategies in the patients with pulmonary adenocarcinoma presenting as pure ground-glass opacities. From January 2006 to December 2010, 1267 patients with pulmonary adenocarcinoma, including adenocarcinoma in situ, underwent curative-intent surgical resection. Among these patients, pure GGNs were confirmed in 48 patients on preoperative chest computed tomography (CT) by an experienced radiologist, and 42 underwent systemic LN dissection or sampling. We retrospectively reviewed the perioperative data and postoperative outcomes. The median age of the patients was 56 (range, 35-78) years, and 26 (54.2%) patients were male. The median size of the nodules was 12 (5-30) mm, and 8 (16.7%) had multiple lesions at the time of operation. The median duration between the initial diagnosis and operation was 4 (0-45) months. Preoperative positron emission tomography/CT was taken in 36 (75.0%) patients, which showed no significant metabolic uptake. For curative resection, lobectomy was performed in 32 (66.7%) patients, segmentectomy in 4, and wedge resection in 12. Clear resection margins were reported in all patients. Forty-two patients underwent systemic mediastinal LN dissection or sampling, and the median number of dissected LNs was 23 (7-53). No LN was reported as positive for malignancy. The median follow-up duration after the first operation was 39 (23-77) months, and there were no cases of late mortality, local recurrence or nodal recurrence. Recurrent GGNs have been developed in 6 (12.5%) patients. For pure GGNs, limited resection can be performed when complete resection is obtained, as it was sufficient for cure and especially because there is high probability of multiple lesions. We were unable to demonstrate any additional therapeutic benefit with mediastinal LN dissection in patients with pure GGNs.

The detection and diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT). Over 80% of 5-year survival rate has been reported in surgically treated peripheral lung cancer. There are systematic mediastinal and hilar lymph node involvement pleural invasion and intrapulmonary metastasis even with tumor diameter less than 2 cm. The appropriate surgical procedure for such kinds of lung cancer is lobectomy with mediastinal lymph node dissection. To evaluate the prognostic factors and establish the optimal surgical strategy, we analyzed the clinicopathologic features and survival benefit in different tumor size of peripheral small-sized NSCLC. Among the resected lung cancer cases between January 1999 and July 2001, 185 patients were retrospectively analyzed in surgical methods, lymph node involvement, CT scan findings and survival rates. Survival was analyzed by Kaplan-Meier method and log-rank test. Lymph node involvement was recognized in 26(14.05%) patients. There was no statistically significant difference in the incidence of lymph node involvement between tumors 1.6-2.0 cm (17.82%) in diameter than in those 1.0-1.5 cm (11.94%). There was no lymph node metastasis in tumors less than 1.0 cm in diameter. The 5-year survival rates with or without lymph node involvement were 89.98 and 46.15%, respectively, showing significant difference (P=0.000). The overall 5-year survival rate was 83.78%. The 5-year survival rate in tumors 1.6-2.0 cm, 1.0-1.5 cm and less than 1.0 cm in diameter was 80.20, 85.07 and 100%, respectively, and showing significant difference (P=0.035). The 5-year survival rate of 19 patients showing ground-glass opacity (GGO) on CT scan was 94.74% without any metastasis and recurrence after operation. There are systematic mediastinal and hilar lymph node involvement even with tumor diameter less than 2 cm. The results of the present study suggested that systematic lymph node dissection is necessary even for cases with tumor diameter less than 2 cm. However, if the tumor is within 1.0 cm in diameter with obvious GGO showing on chest CT scan, these are good candidates for partial resection without mediastinal lymph node dissection.

To investigate the clinical characteristics of thoracic lymph node metastasis in lung cancer. Three hundred and eighteen patients with lung cancer underwent pneumonectomy or lobectomy and lymphadenectomy from Jan 2000 to Jan 2002. A total of 1534 groups of lymph nodes were removed. Metastatic frequency of thoracic lymph nodes was 58.5% (186/318), in which N1 was 27.0% (86/318), N2 was 31.4% (100/318). There were higher frequencies of lymph node metastasis in 4, 7, 10, 11 regions around the root of lung. Among the skipping N2 metastasis (14.5%, 46/318), upper lobe cancer led to only upper mediastinal lymph node metastasis, however, lower or right middle lobe cancer caused both upper and lower mediastinal lymph node metastasis. Of the patients with swelling hilar and mediastinal lymph nodes reported by preoperative CT scan, only 48.2% were confirmed with lymph node metastasis by postoperative histopathology; while 22.4% of the patients with normal size lymph nodes had lymph node metastasis. If there is no hilar and inferior carinal metastatic lymph node in patients with upper lobe cancer, the lower mediastinal lymph node dissection might not be necessary. But systematic mediastinal lymph node dissection should be performed in patients with lower lobe or right middle lobe cancer whether there is hilar or inferior carinal metastatic lymph node or not. The extent of lymph node dissection should not depend on the results of preoperative chest CT scan.

An accurate staging of a malignant disease is imperative in order to plan pre- and post-operative therapy, define prognosis and compare studies. According to the European Society of Thoracic Surgeons (ESTS) guidelines a systematic lymph node (LN) dissection is recommended in all cases of pulmonary resection for non-small cell lung cancer (NSCLC). The current lung cancer staging system considers the lymphatic stations involved but not the number of LNs. Up to date, published scientific studies on hilar and mediastinal lymphadenectomy mainly have been regarded the type of LN dissection procedure after pulmonary resection (selected LN biopsy, LN sampling, systematic nodal dissection, lobe specific nodal dissection and extended LN dissection) focusing particularly on the comparison between mediastinal LN dissection (MLND) and mediastinal LN sampling (MLNS). Recently, further investigations have been concentrated on surgical approach (videothoracoscopic vs. thoracotomic approach) used to perform pulmonary resection and following LN dissection in order to achieve a complete mediastinal lymphadenectomy. This short synthesis aims to present the current experiences in this setting.