pN2 Non-small Cell Lung Cancer Research Articles

Invited Commentary

Invited Commentary

Survival of Patients With Unsuspected pN2 Non-Small Cell Lung Cancer After an Accurate Preoperative Mediastinal Staging

The aim of this study is to analyze the survival of patients with non-small cell lung cancer (NSCLC) without clinical suspicion of mediastinal lymph node involvement who underwent complete resection and whose tumors were finally proven to be pathologic N2 (pN2). This is a retrospective study of a prospective database from January 2004 to December 2010. A total of 621 patients with NSCLC were staged and operated according to the European Society of Thoracic Surgeons guidelines. After exclusions (previous induction treatment, carcinoid tumors, small cell carcinomas), 540 patients were analyzed; 406 (75%) required surgical exploration of the mediastinum and 134 (25%) underwent surgery directly. Survival analysis was performed by the Kaplan-Meier method and the log-rank test was used for comparisons. Thirty (5.5%) patients had unsuspected pN2 and complete resection was achieved in 27 (90%). Three- and 5-year survival rates were 87% and 81%, respectively, for patients with a true negative result of the protocol (pN0-1), and 79% and 40%, respectively, for those with a false negative result (unsuspected pN2) (p < 0.0001). The rate of unsuspected pN2 in patients whose tumors were staged according to the European Society of Thoracic Surgeons guidelines was low. The survival of this group of patients was better than expected. Therefore, resection of properly staged unsuspected pN2 NSCLC is reasonable and should not be avoided if complete resection can be achieved.

Number of Lymph Nodes Associated With Maximal Reduction of Long-Term Mortality Risk in Pathologic Node-Negative Non–Small Cell Lung Cancer

Forty-four percent of patients with pathologic node negative (pN0) non-small cell lung cancer (NSCLC) die within 5 years of curative-intent surgical procedures. Heterogeneity in pathologic nodal examination practice raises concerns about the accuracy of nodal staging in these patients. We hypothesized a reciprocal relationship between the number of lymph nodes examined and the probability of missed lymph node metastasis and sought to identify the number of lymph nodes associated with the lowest mortality risk in pN0 NSCLC. We analyzed resections for first primary pN0 NSCLC in the United States Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2009, with survival updated to December 31, 2009. In 24,650 eligible patients, there was a significant sequential reduction in mortality risk with examination of more lymph nodes. The lowest mortality risk occurred in those with 18 to 21 lymph nodes examined. The hazard ratio for all-cause mortality was 0.65 and the 95% confidence interval (CI) was 0.57 to 0.73; for lung cancer-specific mortality, hazard ratio was 0.62 and CI was 0.53 to 0.73 (p<0.001 for both). The median number of lymph nodes examined was only 6. Lymph node evaluation falls far short of optimal in patients with resected pN0 NSCLC, raising the odds of underestimation of long-term mortality risk and failure to identify candidates for postoperative adjuvant therapy. This represents a major quality gap for which corrective intervention is warranted.

Prognostic impact of lymphovascular invasion compared with that of visceral pleural invasion in patients with pN0 non–small-cell lung cancer and a tumor diameter of 2 cm or smaller

BackgroundBoth visceral pleural invasion (VPI) and lymphovascular invasion (LVI) have been shown to be adverse prognostic factors for early-stage non–small-cell lung cancer (NSCLC). Positive VPI upstages the T category of tumors ≤ 2 cm (T1a) to T2a, whereas LVI is not adapted as a descriptor for the Tumor, Node, Metastasis classification system. This study was conducted to evaluate the prognostic impacts of VPI and LVI in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. MethodsWe reviewed records of a total of 142 patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm, who underwent lobectomy with hilar and mediastinal lymph node dissection between January 2001 and December 2009. We conducted univariate and multivariate analyses to evaluate the impact of VPI, LVI, and other clinicopathologic factors on survival. ResultsVisceral pleural invasion and LVI were diagnosed as positive in 18 (12.7%) and 22 (15.5%) patients, respectively. Male sex, squamous cell carcinoma, positive VPI, and positive LVI were risk factors for overall survival. Squamous cell carcinoma, positive VPI, and positive LVI were risk factors for relapse-free survival. In multivariate analysis, squamous cell carcinoma and positive LVI were independent risk factors for overall survival, and positive LVI was an independent risk factor for relapse-free survival. ConclusionsPositive LVI was more important than VPI as a prognostic factor in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Adjuvant chemotherapy should be considered for such patients, to improve the treatment outcomes.

Mediastinal Lymph-nodes Metastasis beyond the Lobe-specific: An Independent Risk Factor toward Worse Prognoses

Five-year survival rates were widely dispersed in pN2 non-small cell lung cancer (NSCLC). The present study aims to investigate the prognosis of patients with lymph node metastasis beyond lobe-specific mediastinal regions. A total of 654 pathologically proved N2-NSCLC patients were enrolled. All patients underwent a major pulmonary resection and radical mediastinal lymphadenectomy. Two separate groups were assigned according to the definition of lobe-specific nodal metastasis: Group LS (lobe-specific) and Group NLS (non-lobe-specific). Survival rates were calculated using Kaplan-Meier and Cox regression models. There were 376 cases in Group LS and 278 cases in Group NLS. Univariate analyses showed that the risk factors of 5-year survival were operation type, MLN positivity ratio, nodal station, nodal zone, and LS/NLS metastasis. The 5-year survival among those in Group LS was significantly better than that of Group NLS (27.5% vs. 11.7%, p <0.0001). Multivariate analysis confirmed that the grouping method of LS/NLS and number of involved nodal zones were the most prominent risk factors for 5-year survival. Lymph node metastasis beyond lobe-specific lymph nodes is an independent risk factor of 5-year survival and is associated with worse prognoses for N2 NSCLC patients.

Retrospective Analysis of Nodal Spread Patterns According to Tumor Location in Pathological N2 Non‐small Cell Lung Cancer

BackgroundThe purpose of the present study was to determine the nodal spread patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location, and to attempt to evaluate the possible indications of selective lymph node dissection (SLND).MethodsWe retrospectively analyzed nodal spread patterns in 207 patients with NSCLC of less than 5 cm with N2 involvement.ResultsThe tumor location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of upper mediastinal (UM) involvement (96 and 100 %, respectively) and a lower incidence of subcarinal involvement (15 and 10 %, respectively) than lower lobe tumors (UM; RLL 60 %, LLL 42 %; subcarinal: RLL 60 %, LLL 46 %, respectively). Among the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2 showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1, suggesting that UM dissection may be unnecessary in lower lobe tumors with no metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections according to the preoperative T status. Among the patients with 12 subcarinal-positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL or LUD tumors with no metastasis to hilar and UM nodes on frozen sections.ConclusionsThe present study appears to provide one of the supportive results regarding the treatment strategies for tumor location-specific SLND.

Surgical Outcome of Stage IIIA- cN2/pN2 Non–Small-Cell Lung Cancer Patients in Japanese Lung Cancer Registry Study in 2004

The role of surgery in the treatment of non-small-cell lung cancer (NSCLC) with clinically manifested mediastinal node metastasis is controversial even in resectable cases because it is often accompanied by systemic micrometastasis. However, surgery is occasionally indicated for cases with single-station N2 disease or within multimodal treatment regimens, and in clinical trials. The aim of this study is to evaluate surgical outcomes in a modern cohort of patients with clinical (c-) stage IIIA-N2 NSCLC whose nodal metastasis was confirmed by pathology (cN2/pN2). From the central database of lung cancer patients undergoing surgery in 2004, which was founded by the Japanese Joint Committee for Lung Cancer Registration, data of patients having all conditions of NSCLC, c-stage IIIA, cN2, and pN2 were extracted, and the clinicopathologic profile of patients and surgical outcomes were evaluated. Among 11,663 registered NSCLC cases, 436 patients (3.8%) (332 men and 104 women) had been extracted. Their mean age was 65 years, and histologic types included adenocarcinoma (n = 246), squamous cell carcinoma (n = 132), and others (n = 58). The proportion of R0 resection was 82.5% and the proportion of the hospital deaths among the cause of death was 2.3%. The 5-year survival rate was 30.1% for the selected group of patients. The postoperative prognosis was significantly better than those of corresponding populations extracted from the 1994 (p = 0.0001) and 1999 databases (p = 0.0411). Men and women experienced a significantly different survival outcome (p = 0.025) with 5-year survivals of 27.5% and 37.8%, respectively. Single-station N2 cases occupied 60.9 % of the cohort and showed a significantly better prognosis than multistation N2 (p = 0.0053, 35.8 % versus 22.0 % survival rate at 5 years). The surgical outcomes of c-stage IIIA-cN2/pN2 NSCLC patients in 2004 were favorable in comparison with those ever reported.

Survival impact of node zone classification in resected pathological N2 non-small cell lung cancer

We assessed the prognostic value of the 'Zone-classification' which has been proposed by the Japanese Association for Lung Cancer (JALC) for mediastinal nodal metastases in non-small cell lung cancer (NSCLC). Among 357 NSCLC patients who underwent curative surgery, 46 patients with pathological (p) N2 disease were divided into two groups as follows: 32 patients in whom the nearer zone was involved were classified as the pN2a-1 group, and 14 patients in whom the further mediastinal node station was involved were classified as the pN2a-2 group. The proportions of patients with non-adenocarcinoma histology, with multiple station metastases with the involvement of four or more nodes, and who underwent pneumonectomy, were higher in the pN2a-2 group. The 'Zone-classification' proved to be a significant prognostic factor in a univariate analysis (the 5-year overall survival rate, 7.1% for pN2a-2 versus 21.9% for pN2a-1; P < 0.01). A multivariate analysis confirmed that pN2a-2 sub-classification (hazard ratio 2.77; P = 0.03) and undergoing pneumonectomy (hazard ratio 4.86; P < 0.01) were independent and significant factors in predicting a poor prognosis. In pN2 NSCLC patients, the involved mediastinal zone according to the primary tumour site was important in prediction of survival.

Prognostic impact of the primary tumor location based on the hilar structures in non-small cell lung cancer with mediastinal lymph node metastasis

The status of mediastinal lymph node metastasis is one of the main factors determining the treatment strategy for non-small cell lung cancer (NSCLC), but the primary tumor location is not considered crucial in the tumor-node-metastasis (TMN) classification at present. The aim of this study was to estimate the prognostic value of the primary tumor location on the basis of the hilar structures in NSCLC with mediastinal lymph node metastasis. We retrospectively reviewed the cases of 337 consecutive patients who underwent surgical resection for NSCLC between 1995 and 2004, divided the pN2 NSCLC cases (n=40) into central- and peripheral-type tumors according to the distance of the primary tumor from the first branch of the extrapulmonary bronchus, and compared the surgical outcomes between these tumor groups. Eighteen and twenty-two cases were classified as central- and peripheral-type tumors, respectively. The 5-year survival rate was significantly better for patients with central-type tumors than peripheral-type tumors (51.5% vs. 21.2%, P=0.034). The location-specific prognostic tendency was noted irrespective of the presence (n=13) or absence of skip metastasis. In a multivariate Cox analysis of the N2 NSCLC cases, the primary tumor location was a significant (P=0.026) prognostic factor for overall survival. In conclusion, evaluation of the primary tumor location based on the hilar structures is useful to predict the prognosis in N2 NSCLC.

Re-appraisal of N2 disease by lymphatic drainage pattern for non-small-cell lung cancers: By terms of nodal stations, zones, chains, and a composite

PurposeN2 non-small-cell lung cancer (NSCLC) is a heterogeneous disease with an extremely wide range of 5-year survival rates. A composite method of sub-classification for N2 is likely to provide a more accurate method to more finely differentiate prognosis of N2 disease. MethodsA total of 720 pN2 (T1-4N2M0) NSCLC cases were enrolled in our retrospective analysis of the proposed composite method. Survival rates were respectively calculated according to the N2 stratification methods: singly by “nodal stations”, “nodal zones”, or “nodal chains”, or by combination of all three. Statistical analysis was carried out by Kaplan–Meier and Cox regression models. ResultsA total of 10,199 lymph nodes (8059 mediastinal; 2140 hilar and intra-lobar) were removed. By nodal station, there were 173 cases of single-station involvement and 547 multi-stations. By nodal zone, there were 413 single-zone involvement and 307 with multiple zones. By nodal chain, there were 311 cases with single-chain and 409 multi-chain involvements. The overall 5-year survival was 20% and median survival time was 27.52 months. The 5-year survival was significantly better for cases of single-zone involvement, as compared to multi-zones (29% vs. 6%, p<0.0001). The 5-year survival rates of single- and multi-chains involvement were 36% and 8%, respectively (p<0.0001). When taking all of the above grouping methods into consideration, the N2 disease state could be further sub-classified into two subgroups with respective survival rates of 36% and 7% (p<0.0001). Subgroup I was composed of individuals with single-chain involvement and having either one or two station metastasis; individuals with any other metastasis combinations formed Subgroup II. Multivariate analysis revealed that the composite sub-classification method, number of positive lymph nodes, ratio of nodal metastasis, and pT information were the most important risk factors of 5-year survival. ConclusionsBy combining the three N2 stratification methods based on “stations”, “zones”, and “chains” into one composite method, prognosis prediction was more accurate for N2 NSCLC disease. Single nodal chain involvement, which may be either one or two nodal stations metastasis, is associated with best outcome for pN2 patients.

Prognostic Impact of Node Involvement Pattern in pN1 Non-small Cell Lung Cancer Patients

We previously showed that squamous cell carcinoma (SCC) patients with directly involved N1 nodes resulted in outcomes significantly better than those with separately involved N1 nodes. The purpose of this study was to evaluate the prognostic effect of node involvement patterns in pN1 non-small cell lung cancer (NSCLC) patients, with special attention given to any differences between SCC and adenocarcinoma (AD). We reviewed 324 consecutive patients with completely resected pN1 NSCLC and classified them into two groups based on their node involvement patterns: directly or separately involved N1 groups. To compare survival rates, 1545 pN0 patients and 330 pN2 patients were also investigated. Univariate and multivariate analyses showed that the node involvement pattern was significantly associated with pN1 NSCLC patient outcome. The directly involved N1 group had a much better 5-year overall survival rate of 60.1% compared with 45.0% for the separately involved N1 group. In SCC patients, the directly involved N1 group showed an overall survival similar to pN0 patients, whereas overall survival of the separately involved N1 group was identical to that of pN2 patients, and their survival rates were significantly different. In AD patients, however, the survival rates were marginally different between the directly and separately involved N1 groups, and they were intermediate between pN0 and pN2 patient survival rates. Node involvement patterns had significant prognostic effect in pN1 NSCLC patients. This effect was different between SCC and AD cases. The subclassification of N1 based on node involvement pattern is of significance for SCC patients but not for AD patients.

High Dose Post Operative Radiotherapy in pN2 Non-small Cell Lung Cancer

High Dose Post Operative Radiotherapy in pN2 Non-small Cell Lung Cancer

Prognostic Stratification of Stage IIIA pN2 Non-small Cell Lung Cancer by Hierarchical Clustering Analysis of Tissue Microarray Immunostaining Data: An Alpe Adria Thoracic Oncology Multidisciplinary Group Study (ATOM 014)

Stage IIIA non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node metastases (N2) is a heterogeneous disease with differing prognoses. In this study, we retrospectively investigated the prognostic value of the expression of 10 molecular markers in 87 patients with stage IIIA pN2 NSCLC treated with radical surgery. Primary tumor tissue microarrays (TMAs) were constructed and sections used for immunohistochemical analysis of epidermal growth factor receptor, ErbB-2, c-kit, cyclooxygenase-2, survivin, bcl-2, cyclin D1, cyclin B1, metalloproteinase (MMP)-2, and MMP-9. Univariate and multivariate analyses and unsupervised hierarchical clustering analysis of clinical pathologic and immunostaining data were performed. Bcl-2 (p < 0.0001) and cyclin D1 (p = 0.015) were more highly expressed in squamous cell carcinoma (SCC), whereas MMP-2 (p = 0.009), MMP-9 (p = 0.005), and survivin (p = 0.032) had increased expression in other histologic subtypes. In univariate analysis, SCC histology and cyclin D1 expressions were favorable prognostic factors (p = 0.015 and p < 0.0001, respectively); by contrast, MMP-9 expression was associated with worse prognosis (p = 0.042). In multivariate analysis, cyclin D1 was the only positive prognostic factor (p < 0.0001). Unsupervised hierarchical clustering analysis of TMA immunostaining data identified five distinct clusters. They formed two subsets of patients with better (clusters 1 and 2) and worse (clusters 3, 4, and 5) prognoses, and median survival of 51 and 10 months, respectively (p < 0.0001). The better prognosis subset mainly comprised patients with SCC (80%). Hierarchical clustering of TMA immunostaining data using a limited set of markers identifies patients with stage IIIA pN2 NSCLC at high risk of recurrence, who may benefit from more aggressive treatment.

Adjuvant Chemotherapy in New Stage II pN0 Non-small Cell Lung Cancer: A New Issue for a Case-By-Case Decision Making Process

Adjuvant Chemotherapy in New Stage II pN0 Non-small Cell Lung Cancer: A New Issue for a Case-By-Case Decision Making Process

Prognostic Factors for Resected Non-Small Cell Lung Cancer with pN2 Status: Implications for Use of Postoperative Radiotherapy

For non-small cell lung cancer (NSCLC) patients with pN2 status, the use of postoperative radiotherapy (PORT) remains controversial. Here, we investigated the association between different clinicopathological features and postoperative therapy and local control and survival in patients with resected pN2 NSCLC. We retrospectively analyzed 83 patients with pN2 NSCLC who underwent resection at Vanderbilt University Medical Center between 1994 and 2004. The relationship between 10 prognostic factors-gender, age at diagnosis, histology, tumor size, number of nodal stations involved, positive node number, surgical margin, extracapsular extension (ECE), and use of postoperative chemotherapy and PORT-and 2-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), and overall survival (OS) rates was evaluated. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and Cox proportional hazards ratios, respectively. On univariate analysis, PORT was significantly associated with greater LRFS, RFS, and OS rates, whereas chemotherapy was associated with a trend toward a higher OS rate. Negative surgical margins were predictive of a higher OS rate, and negative ECE was associated with higher LRFS and RFS rates. On multivariate analysis, only PORT and negative ECE were associated with a higher LRFS rate. On subgroup analysis, in negative ECE patients, PORT was significantly associated with a higher OS rate. PORT is associated with a higher OS rate for patients with resected pN2 NSCLC with negative ECE but not with positive ECE. The absence of ECE may serve as a useful prognostic variable in the selection of pN2 NSCLC patients for PORT and warrants further investigation in randomized clinical trials.

9105 Phase III study of concurrent chemoradiotherapy followed by surgery (S) vs. chemotherapy (C) followed by S for stage IIIA (pN2) non-small cell lung cancer (NSCLC): results of prematurely terminated trial, WJTOG9903

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70 years or older with a newly diagnosed GBM were treated with radiotherapy (60 Gy in 16 patients and 40 Gy in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8 months (95% confidence interval [CI], 8.7–14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0 months (95% CI, 2.4–3.5), and the time to ECOG performance status grade 3 was 5.8 months (95% CI, 1.6–9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%), leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p = 0.003) and a longer time with good performance status for gross total removal (GTR) (p = 0.003). An initial good performance status was related to a good performance status during and after treatment (p = 0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR] = 0.236; 95% CI, 0.060–0.922, p = 0.038) and a good performance status (HR = 0.124; 95% CI, 0.022–0.693, p = 0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.

Phase III study of induction chemotherapy (docetaxel and carboplatin) with or without radiotherapy followed by surgery in patients with stage IIIA (pN2) non-small cell lung cancer (NSCLC): WJTOG9903

7556 Background: Standard treatment of resectable N2 disease is not yet established. To gain insights on significance of preoperative chemoradiotherapy, we tried to evaluate feasibility and efficacy of induction chemotherapy with or without radiotherapy followed by surgery in patients with stage IIIA NSCLC with mediastinal lymph node metastases. Methods: Patients with histologically proven N2 disease were randomized either to receive induction chemotherapy (taxotere 60 mg/m2 and carboplatin AUC 5x2 cycles) with concurrent radiation therapy of 40Gy/20fr (CRS group) or without it (CS group). Patients subsequently underwent pulmonary resection if the tumor was judged resectable. Original sample size was 180 to detect a 20% of survival difference (2 sided P=0.05) with a power of 0.8. The primary endpoint was overall survival. Results: Between Jan. 2001 and Dec 2005, 60 patients were randomized Because of poor accrual of the patients, the study was prematurely terminated. Two patients assigned to CRS group were ineligible due to staging misconducts. Median age was 57 years (range 34–70 years), and 66% were male. Two groups were well balanced with regard to age, gender, histology, and operative procedures. Induction therapy was well tolerated, and there was no treatment related death. Grade 3 and 4 neutropenia occurred in 74 and 89%, respectively. Objective response rate was 25% for the both groups. Surgical resection was performed in 86% and 89%of the patients in CS and CRS groups, respectively. There have been 37 deaths to date. Event free survival at 3 year was 18% and 32% for patients in CS and CRS group, respectively (HR=0.64; 95% CI: 0.36–1.17, P=0.15). Overall survival at 3 year was 44.4 %. and 52.7% (HR=0.84; 95% CI: 0.44–1.62, P=0.62), respectively. Conclusions: Because of small sample size, there was no statistically significant difference. However, our study suggested that addition of radiotherapy to induction chemotherapy could potentially prolong survival of NSCLC patients with N2 disease. [Table: see text]

Gene Diagnosis and Prognostic Significance of Lymph Node Micrometastasis after Complete Resection of Histologically Node‐negative Non‐small Cell Lung Cancer

The purpose of the present study was to investigate the prevalence of lymph node micrometastasis (LNMM) based on the detection of MUC1 mRNA, and assess the impact of these micrometastases on prognosis after resection of pathologic N0 (pN0) non-small cell lung cancer (NSCLC). The subjects were 89 patients who underwent complete resection of pN0 NSCLC at our department between January 2000 and January 2002. All lymph nodes (402 stations) obtained from these patients were re-evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1 mRNA. The diagnosis of LNMM was based on the detection of MUC1 mRNA. The Kaplan-Meier method was used to calculate the survival rate, and Cox regression multivariate analysis was performed to determine independent prognostic factors. Micrometastases were detected in 36 lymph node stations (9.0%) from 21 patients (23.6%). The TNM staging of these 21 patients was upregulated from stage IA-IIB to stage IIIA. The 5-year survival rate of patients with LNMM was significantly lower than that of patients without LNMM (23.8% versus 44.1%; p < 0.05). The results of multivariate analysis confirmed that T status, histology, and LNMM were independent prognostic factors. The prevalence of LNMM in patients with pN0 NSCLC was 23.6% (21/89). T status, histology, and LNMM were independent prognostic factors.

Detecção de micrometástases em câncer de pulmão não-pequenas células estádio pN0: um método alternativo combinando imunohistoquímica e análise em microsséries

To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining. A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry. Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50%) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified. The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.

Superior and Basal Segment Lung Cancers in the Lower Lobe Have Different Lymph Node Metastatic Pathways and Prognosis

Although the lower lobe is a large entity that occupies half of the hemithorax, all tumors located within the lower lobe have been treated uniformly regardless of tumor location. The aim of this study was to reveal differences in the metastatic pathway to the mediastinum and in prognosis of N2 disease between lung cancers originating from superior and basal segment of the lower lobe. Data on 139 patients who underwent pulmonary resection with systematic nodal dissection for pN2 non-small cell lung cancer (NSCLC) originating from the lower lobe between 1980 and 2001 were retrospectively reviewed. Those lower lobe N2 tumors were divided into two groups by origin: 51 were superior segment, and 88 were basal segment. The superior segment group showed a significantly higher incidence of superior mediastinal metastasis than the basal segment group (64% vs 36%, p = 0.0012). When superior mediastinal metastasis existed, the basal segment group showed a significantly higher incidence of synchronous subcarinal metastasis than the superior segment group (81% vs 39%, p = 0.0006). Pneumonectomy was required significantly more often in the superior segment group than in the basal segment group (45% vs 17%, p = 0.0003). The basal segment origin tumors with only subcarinal metastasis showed significantly better prognosis than other lower lobe N2 tumors (5-year survival, 43% vs 18%; p = 0.0155). Basal segment tumor metastasizes to the superior mediastinum mostly through the subcarinal node, whereas superior segment tumors often metastasize directly to the superior mediastinum without concomitant metastasis to the subcarinal node. Superior mediastinal dissection will be mandatory for accurate staging of superior segment tumors even when the subcarinal node is negative on frozen section. As for the prognosis among lower lobe N2 tumors, only in cases with basal segment tumor without superior mediastinal metastasis may long-term survival be expected.