The significance of ipsilateral mediastinal lymph node metastasis (N2 disease) in non-small cell carcinoma of the lung. A commentary

The significance of the presence of N2 disease in patients with non-small cell cancer of the lung is widely misunderstood. Long-term survival rates from 15% to more than 30% after surgical resection are frequently reported in the literature. However, these percentages represent only the surgical results in a highly selected and unfortunately small proportion of the entire number of patients with N2 disease. In those patients in whom N2 disease is readily clinically recognizable or is identified by standard roentgenographic or bronchoscopic study and proved by biopsy or is discovered by prethoracotomy mediastinal exploration, a 5-year survival rate of only approximately 2% for the entire group can be expected, even when aggressive surgical resection is performed when appropriate. In those patients in whom the N2 disease is only initially recognized at thoracotomy, the resectability rate is higher and 5-year survival rates as noted are in the range of 15% to 30%. Although surgical resection continues to be the primary choice of therapy in this small group (less than 20% of patients with N2 disease), surgical resection can be expected to salvage only 3% to 6% of all patients with N2 disease. Thus, with presently available therapy, the vast majority of patients proved to have N2 disease will die of their lung cancer. It must be concluded that N2 disease is a significant poor prognostic factor in patients with lung cancer.     

Results of resection in non-oat cell carcinoma of the lung with mediastinal lymph node metastases.

From 1974 to 1981, 1598 patients with non-oat cell carcinoma of the lung were seen and treated. All were staged according to the AJC staging system. Of these, 706 patients had evidence of mediastinal lymph node metastases (N2). There were 151 patients (21%) who had complete, potentially curative resection of their primary tumor and all accessible mediastinal lymph nodes. The histologic type of tumor was adenocarcinoma in 94 patients, epidermoid carcinoma in 46 patients, and large-cell carcinoma in 11 patients. The extent of pulmonary resection consisted of a lobectomy in 119 patients, pneumonectomy in 26 patients, and wedge resection or segmentectomy in six patients. Almost all patients also received radiation therapy to the mediastinum. Clinical staging of the primary tumor and the mediastinum was based on the radiographic presentation of the chest and on bronchoscopy. Before treatment, 104 of 151 patients (69%) were believed to have had stage I (90 patients) or II (14 patients) disease, and 47 patients had stage III disease, of whom only 33 had evidence of mediastinal lymph node involvement. Excluding deaths from unrelated causes, the overall survival rate was 74% at 1 year, 43% at 3 years and 29% at 5 years. Survival in patients with clinical stage I or II disease treated by resection was favorable despite the presence of N2 nodes (50% at 3 years). Survival in obvious clinical N2 disease was poor (8% at 3 years). There was no difference in survival between patients with adenocarcinoma and those with epidermoid carcinoma. However, survival was poorer in patients with N2 nodes in the inferior mediastinum compared to those without lymph node involvement at that level.     

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

Analysis of T1N0M0 nonsmall cell lung cancer undergoing surgical resection without mediastinal lymph node dissection

Eleven patients of T1N0M0 non-small cell lung cancer underwent relatively non-curative surgical resection without mediastinal lymph node dissection (the undissected group). The 5 year survival rate of this group was 70.7% and no significant difference in survival was found between the undissected group and the patients of T1N0M0 non-small cell lung cancer undergoing absolutely curative surgical resection (the dissected group). No patient died of pneumonia in the undissected group, while 4 aged patients in the dissected group died of pneumonia. This may suggest that mediastinal lymph node dissection is also injurious in distant period after surgery, especially in the aged patient. So "simple lobectomy" without mediastinal lymph node dissection may be considered as an elective procedure in the poor risk patient such as the aged, who has an early staged non-small cell lung cancer.     

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer.

OBJECTIVE: Impacts of mediastinal lymph node dissection on a patient's course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. METHODS: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. RESULTS: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. CONCLUSION: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

Resectional surgery in the treatment of primary carcinoma of the lung with mediastinal lymph node metastases.

Between 1966 and 1970 we reviewed 46 consecutive patients undergoing resection for primary carcinoma of the lung, in whom mediastinal lymph node metastases were found at operation. There was one operative death. Five of the remaining 45 patients survived five years--one of 10 cases of large cell carcinoma, one of 19 cases of adenocarcinoma, and three of 12 cases of epidermoid carcinoma. We believe that mediastinal lymph node metastases are not per se a contraindication to resection of epidermoid carcinoma of the lung.     

Surgery in the treatment of pulmonary carcinoma with mediastinal lymph node metastasis (N2)]

This study is based on the analysis of the survival data in patients with N2 disease reported by Martini, Pearson, Shields et al. Many factors appear to influence survival of this group of patients. We made a retrospective analysis of a series of 91 patients with N2 disease between January 1980 and March 1985. Sixty-nine patients (71.5%) presented clinically N2 disease; 44 patients (63.7%) were treated with complete resection and postoperative irradiation, the actuarial five year survival was 11%. Twenty-two patients (24.2%) were discovered to have N2 disease at thoracotomy. Twenty-one patients underwent resection and the actuarial five year survival was 29%. We conclude that surgery can be effective in a highly selective group of patients.     

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.     

Endoscopic ultrasonography for preoperative diagnosis of the hilar and mediastinal lymph node metastases in lung cancer]

Fifty patients with lung cancer underwent transesophageal endoscopic ultrasonography (EUS) for preoperative detection of metastases to the hilar and mediastinal lymph nodes. An electronic ultrasonic fiberscope with a linear array (EPB-503-FS, Machida-Toshiba) was used. Later, in surgery, a total of 513 nodes that could have been detected by EUS were removed. Of these, 54 nodes were found to be metastatic histologically, and 459 were non-metastatic. The rate of detection by EUS was 65% (35/54) for the metastatic nodes; the rate was 41% (186/459) for the non-metastatic nodes (p less than 0.01). Metastatic nodes were detected at high rates in every lymph node site. Non-metastatic nodes were detected at low rates in sites 1, 2, and 4, and at the highest rate in site 7. Metastatic nodes had characteristic internal echoes, affected by the extent of tumor and necrosis present in a node, and were detected more easily than non-metastatic nodes. For larger or rounder nodes, metastasis was more common (p less than 0.01). Lymph nodes that could be detected were classified into six types by their internal echo patterns; three of these types were rarely metastatic, and were called 'negative'; the other three were often metastatic, and were called 'positive'. In histological examinations, of the 'negative' nodes found in fact to be metastatic histologically, invasion by the tumor tended to be diffuse and necrosis was minute. The 'positive' nodes that were in fact metastatic tended to have one of two internal echo patterns (depending on the amount of necrosis) when invasion was diffuse, and a third pattern when invasion was localized.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prognostic value of carcinoembryonic antigen in T1N1M0 and T2N1M0 non-small cell carcinoma of the lung.

OBJECTIVE: To evaluate the significance of preoperative clinicopathological factors, including serum carcinoembryonic antigen (CEA), as well as postoperative clinicopathological factors in T1-2N1M0 patients with non-small cell lung cancer who underwent curative pulmonary resection. METHODS: Twenty T1N1M0 disease patients and 25 T2N1M0 patients underwent standard surgical procedures between September 1996 and December 2005, and were found to have non-small lung cancer. As prognostic factors, we retrospectively investigated age, sex, Brinkman index, histologic type, primary site, tumor diameter, clinical T factor, clinical N factor, pathological T factor, preoperative serum CEA levels, surgical procedure, visceral pleural involvement, and the status of lymph node involvement (level and number). RESULTS: The overall 5-year survival rate of all patients was 59.6%. In univariate analysis, survival was related to age (<70/>or=70 years, p=0.0079), site (peripheral/central, p=0.043), and CEA level (<5.0/>or=5.0 ng/ml, p=0.0015). However, in multivariate analysis, CEA (<5.0/>or=5.0 ng/ml) was the only independent prognostic factor; the 5-year survival of the patients with an elevated serum CEA level (>or=5.0 ng/ml) was only 33.2% compared to 79.9% in patients with a lower serum CEA level (<5.0 ng/ml). CONCLUSIONS: An elevated serum CEA level (>or=5.0 ng/ml) was an independent predictor of survival in pN1 patients except for T3 and T4 cases. Therefore, even in completely resected pN1 non-small cell lung cancer, patients with a high CEA level might be candidates for multimodal therapy.     

ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer.

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC) is of paramount importance. It will guide choices of treatment and determine prognosis and outcome. Over the last years, different techniques have become available. They vary in accuracy and procedure-related morbidity. The Council of the ESTS initiated a workshop on preoperative mediastinal lymph node staging. This resulted in guidelines for primary staging and restaging. For primary staging, mediastinoscopy remains the gold standard for the superior mediastinal lymph nodes. Invasive procedures can be omitted in patients with peripheral tumors and negative mediastinal positron emission tomography (PET) images. However, in case of central tumors, PET hilar N1 disease, low fluorodeoxyglucose uptake of the primary tumor and LNs > or = 16 mm on CT scan, invasive staging remains indicated. PET positive mediastinal findings should always be cyto-histologically confirmed. Transbronchial needle aspiration (TBNA), ultrasound-guided bronchoscopy with fine needle aspiration (EBUS-FNA) and endoscopic esophageal ultrasound-guided fine needle aspiration (EUS-FNA) are new techniques that provide cyto-histological diagnosis and are minimally invasive. Their specificity is high but the negative predictive value is low. Because of this, if they yield negative results, an invasive surgical technique is indicated. However, if fine needle aspiration is positive, this result may be valid as proof for N2 or N3 disease. For restaging, invasive techniques providing cyto-histological information are advisable despite the encouraging results supported with the use of PET/CT imaging. Both endoscopic techniques and surgical procedures are available. If they yield a positive result, non-surgical treatment is indicated in most patients.     

纵隔淋巴结清扫对Ⅰ期非小细胞肺癌预后的影响

目的探讨纵隔淋巴结清扫范围对I期非小细胞肺癌预后的影响。方法回顾性分析从1994年1月至2003年12月在我院接受手术切除的330例I期非小细胞肺癌患者的临床、病理和随访资料。根据纵隔淋巴结清扫范围将全组患者分为纵隔淋巴结清扫组（LND）和淋巴结取样组（LNS）。运用Kaplan—Meier生存分析和COX比例风险模型,对影响预后的因素进行单因素和多因素分析。结果本组患者男性233例,女性97例;中位年龄60岁。IA期98例,IB期232例。LND组140例,LNS组190例;平均每例患者淋巴结清扫个数两组分别为（13,3±4,7）个和（5,2±3,0）个（P〈0,01）;平均每例患者纵隔淋巴结清扫组数两组分别为（3．7±0,9）组和（1．3±1．1）组（P〈0．01）。LND组5年和10年生存率分别为72,0％和66,1％,LNS组为65,9％和43．0％（P〈0,05）。其他影响预后的因素包括诊断时是否出现症状、肿瘤分期、是否侵犯脏层胸膜和肿瘤大小。COX比例风险模型分析结果显示,淋巴结清扫范围和术前有无症状是影响预后的因素。结论纵隔淋巴结清扫可以提高I期非小细胞肺癌术后的生存率。     

Segmentectomy for c-T1N0M0 non-small cell lung cancer

While the use of segmentectomy to treat lung cancer remains controversial, it has recently gained status as a radical surgery for cT1aN0M0 non-small cell lung cancer. I herein review the literature regarding segmentectomy and present my data to discuss the following issues: the prognosis after segmentectomy; local recurrence; the area required for lymph node dissection at the hilum and mediastinum; the technique used to cut the intersegmental plane; the selection of the lymph nodes for frozen sections; the postoperative pulmonary function; the role of completion lobectomy after radical segmentectomy for cT1N0M0/pN1-2; expectations and concerns regarding the randomized controlled trial JCOG0802; and the future of segmentectomy.