Pathologic N2 Disease Research Articles

Postoperative radiotherapy for primary early oral tongue cancer with pathologic N1 neck

The benefit of postoperative radiotherapy (PORT) for early squamous cell carcinoma of the tongue (SCCOT) with pathologic N1 disease remains unclear. The medical records of all patients with pathologic T1-2/N0-1 SCCOT who underwent wide excision of the primary tumor and neck dissection between 1980 and 2002 were reviewed. There were 59 patients analyzed, including 28 patients with and 31 patients without PORT. The 5-year disease-free survival rates were 81.2% and 53% for the patients with and without PORT, respectively (p = .03). The overall 5-year survival rates were 77% and 70.5% for the patients with and without PORT, respectively (p = .36). Multivariate analyses showed that PORT had the only protective effect (p = .01) and extracapsular spread (ECS) was the only significantly adverse factor for locoregional recurrence (p = .03). Approximately one-third of the patients who received only surgery had locoregional recurrence. PORT significantly improved the disease-free survival.

Outcomes of the Initial Surgical Treatment without Neoadjuvant Therapy in Patients with Unexpected N2 Non-small Cell Lung Cancer

Background: Preoperative chemotherapy has been adopted in our hospital as a standard treatment for non-small cell lung cancer patients with N2 disease. However, there have been cases of pathologic N2 disease that have been detected after curative-intent surgical resection. We retrospectively studied the outcomes of initial surgical treatment without neoadjuvant therapy in patients with unexpected N2 non-small cell lung cancer. Material and Method: Between January 1995 and June 2007, 225 patients were diagnosed with pathologic N2 disease after they underwent initial pulmonary resection without neoadjuvant therapy. Among them, 170 patients were preoperatively diagnosed with lymph node stage N0 or N1. We retrospectively reviewed their medical record and analyzed the outcomes. Result: The overall 5-year survival rate was 35.4%. The prognostic factors that were significantly associated with survival were no adjuvant therapy, histologic cell types other than adenocarcinoma or squamous cell carcinoma, a pathologic T stage more than T1, old age (≥70 years) and no mediastinoscopic biopsy. During the follow-up, 79 patients (46.5%) experienced tumor recurrence, including loco-regional recurrence in 20 patients (25.3%) and distant metastasis in 56 (70.9%). The 5-year recurrence-free survival rate was 33.7%. Conclusion: Based on our findings, the survival was good for patients with unexpected N2 non-small cell lung cancer and who underwent initial pulmonary resection without neoadjuvant therapy. A prospective comparative analysis is needed to obtain more conclusive and persuasive results.

Long-Term Results of Sleeve Lobectomy in the Management of Non–Small Cell Lung Carcinoma and Low-Grade Neoplasms

The objective of this study was to evaluate the operative mortality, morbidity, and long-term survival of sleeve lobectomy for non-small cell lung cancer and low-grade neoplasms. We evaluated the effects of neoadjuvant therapy on the bronchial anastomotic complication rate and determined whether sleeve lobectomy performed in patients with N1 disease resulted in decreased overall survival. This study is a retrospective review of 196 patients who underwent sleeve lobectomy. One hundred twenty-five patients had non-small cell lung cancer. There were 117 men (59.7%) and 79 women (40.3%) with a mean age of 54 years. Sixteen patients (13%) received neoadjuvant therapy. Fifty-six patients with N1 disease underwent sleeve lobectomy. There were 4 (2.0%) postoperative deaths. The postoperative morbidity rate was 36.7%. Four patients (2.0%) experienced bronchopleural fistulas. Multivariate analysis demonstrated that age older than 70 years (p = 0.02) and the diagnosis of non-small cell lung cancer (p = 0.0002) were risk factors for postoperative complications. Multivariate analysis also demonstrated that neoadjuvant therapy predicted anastomotic complications (p = 0.01). For non-small cell lung cancer patients, the 5-year survival rate was 44%. The 5-year survival rates for patients with pathologic N0 disease and N1 disease were 52.6% versus 39.3%, respectively (p = 0.205). Sleeve lobectomy can be performed with minimal bronchial anastomotic complications and low postoperative mortality. In our study, neoadjuvant therapy for non-small cell lung cancer adversely influenced the rate of anastomotic complications. Performing sleeve lobectomy for patients with N1 disease was not associated with decreased overall survival rates.

Difference of Sentinel Lymph Node Identification Between Tin Colloid and Phytate in Patients With Non–Small Cell Lung Cancer

The advantages and disadvantages of technetium Tc 99m tin colloid and technetium Tc 99m phytate as tracers for sentinel node (SN) identification in patients with clinical stage I non-small cell lung cancer were examined retrospectively. Sentinel node identification was conducted using tin colloid and phytate, respectively, in 73 and 74 patients with clinical stage I non-small cell lung cancer. We compared these two tracers in terms of identification rates, numbers of SNs, characteristics of patients whose SNs could not be identified, and the pathologic results of SNs. The tin colloid tracer identified SNs in 54 of the 73 patients (74%), which was significantly lower than the 89% (66 of 74 patients) in the phytate group (p = 0.02). The number of SNs per patient was 1.7 +/- 0.8 in the tin colloid group, which was significantly less than the 2.4 +/- 1.5 in the phytate group (p = 0.002). Although patients in the tin colloid group whose SNs could not be identified had a significantly lower forced expiratory volume in 1 second to forced vital capacity ratio than those whose SNs could be identified (p = 0.04), the phytate group did not show such a difference. Eleven of 120 patients whose SNs could be identified had pathologic N1 or N2 disease, but neither group showed any false-negative results for SN identification. Both tin colloid and phytate are reliable tracers for identifying SNs in non-small cell lung cancer. The advantage of phytate is that SNs can be detected more frequently than with tin colloid, even in patients with a low forced expiratory volume in 1 second to forced vital capacity ratio. However, tin colloid requires fewer nodes than phytate to identify SNs.

Invited Commentary

Invited Commentary

Persistent N2 Disease After Induction Therapy Does Not Jeopardize Early and Medium Term Outcomes of Pneumonectomy

Operative management of patients with persistent N2 disease after induction therapy is still debated. One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates. Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy. Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy.

FDG PET/CT and Mediastinal Nodal Metastasis Detection in Stage T1 Non-Small Cell Lung Cancer: Prognostic Implications

ObjectiveWe aimed to compare the prognoses of patients with pathologically true negative (P-TN) N2 and PET/CT false negative (FN) results in stage T1 non-small cell lung cancer (NSCLC).Materials and MethodsOur institutional review board approved this retrospective study with a waiver of informed consent. The study included 184 patients (124 men and 60 women; mean age, 59 years) with stage T1 NSCLC who underwent an integrated PET/CT and surgery. After estimating the efficacy of PET/CT for detecting N2 disease, we determined and compared disease-free survival (DFS) rates in three groups (P-TN [n = 161], PET/CT FN [n = 12], and PET/CT true positive [TP, n = 11]) using the Kaplan-Meier analysis and log-rank test.ResultsPathologic N2 disease was observed in 23 (12%) patients. PET/CT had an N2 disease detection sensitivity of 48% (11 of 23 patients), a specificity of 95% (153 of 161), and an accuracy of 89% (164 of 184). The 3-year DFS rate in the PET/CT FN group (31%, 95% confidence interval [CI]; 13.6-48.0%) was similar to that of the TP group (16%, 95% CI; 1.7-29.5%) (p = 0.649), but both groups had significantly shorter DFS rates than the P-TN group (77%, 95% CI; 72.0-81.2%) (p < 0.001).ConclusionThe PET/CT shows a high specificity, but low sensitivity for detecting N2 disease in stage T1 NSCLC. Patients with PET/CT FN N2 disease have survival rates similar to PET/CT TP N2 disease patients, which are both substantially shorter than the survival rate of P-TN patients.

Accessing the Aortopulmonary Window (#5) and the Paraaortic (#6) Lymph Nodes in Patients With Non-Small Cell Lung Cancer

The purpose of this study was to assess the efficacy of the different techniques of lymph node biopsies in patients with suspected metastatic non-small cell lung cancer (NSCLC) in the subaortic (station #5) and paraaortic (station #6) lymph nodes. This was a retrospective cohort study conducted of a prospective database of patients between January 2003 and June 2006 with suspected N2 disease only in the #5 or #6 lymph nodes, or both. All patients had integrated 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography, and nodal biopsy or thoracotomy, or both, with complete thoracic lymphadenectomy. There were 112 patients with clinically suspected N2 disease in lymph node stations #5 or #6, or both. The primary tumor was in the left upper lobe in 98 (88%) and in the left lower lobe in 14 (13%), and 58 had pathologic N2 disease in #5 or #6 lymph node stations only. Mediastinoscopy, used in all patients found, unsuspected N3 disease in 4 patients (3.6%) and N2 (#4L) disease in 12 (11%). Endoscopic ultrasound with fine needle aspiration (EUS-FNA), implemented in 62 patients (56%), correctly identified 41 patients (66%). Left single-incision video-assisted thoracic surgery (VATS) was used in 39 patients and was correct in 100%. Of the 58 patients, 53 (91%) completed neoadjuvant chemoradiotherapy, followed by resection, and their 5-year survival was 64%. EUS-FNA is less accurate for the #5 and #6 lymph node stations than left VATS. We prefer left VATS over the Chamberlain procedure for patients with suspected nodal metastases isolated only to #5 or #6 stations, and if positive, we prefer neoadjuvant therapy. The advantage of neoadjuvant therapy followed by resection compared with resection followed by adjuvant therapy remains controversial; and hence, the role for biopsy of these nodes is also controversial.

Sentinel node identification in clinical stage Ia non–small cell lung cancer by a combined single photon emission computed tomography/computed tomography system

A gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, owing to high radioactivity from primary tumors. We evaluated the utility of fused single photon emission computed tomography/computed tomography (SPECT/CT) images for the identification of sentinel nodes in the hilum for patients with clinical stage Ia non-small cell lung cancer. Technetium-99m tin colloid was injected into the peritumoral region approximately 18 hours before surgery in 63 patients with clinical stage Ia non-small cell lung cancer. On the morning of the operation, approximately 16 hours after administration of tin colloid, sentinel nodes were identified by fused SPECT/CT; this was followed by intraoperative sentinel node identification in the dissected lymph nodes by gamma probe. Because the gamma probe is a standard method for sentinel node identification, the sensitivity of fused SPECT/CT images was examined on the basis of the data of the gamma probe. Fused SPECT/CT images could identify sentinel nodes at segmental and lobar lymph nodes with a sensitivity of 0.87 and 0.74, both of which were significantly higher than 0.40 in the mediastinum (P < .001 and P = .012, respectively). In 5 patients with pathologic N1 or N2 disease, both SPECT/CT and the gamma probe could identify sentinel nodes with metastases. SPECT/CT could identify sentinel nodes of the hilum especially in segmental and lobar lymph nodes but not in the mediastinum. Because the gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, a combination of SPECT/CT and the gamma probe can be used to identify sentinel nodes before nodal dissection in both the hilum and the mediastinum, which will enable sentinel node navigation surgery in non-small cell lung cancer.

The NATCH trial: Observations on the neoadjuvant arm

7578 Background: In early-stage NSCLC the neoadjuvant approach is a promising option since relatively low compliance rate with adjuvant therapy and incomplete recovery after surgery are commonly reported. The NATCH trial was therefore designed to address whether neoadjuvant or adjuvant paclitaxel (P)/carboplatin (C) improves disease-free survival compared to surgery alone in early-stage NSCLC. Patients randomized to the neoadjuvant arm have now undergone analyses of toxicity, radiographic response, resectability and surgical mortality. Methods: Consenting patients with clinical stage I (&gt;2 cm), II, T3N1 NSCLC are randomized to surgery alone or 3 cycles of neoadjuvant PC (P: 200 mg/m2/ C:AUC=6 on day 1 every 3wk), or surgery followed by 3 cycles of adjuvant PC at the same schedule. Planned sample size of this prospective, randomized trial is 628 patients. Results: Since 2000, 616 patients have been accrued, 200 in the neoadjuvant arm, 208 in the adjuvant arm, and 208 in the surgery arm. Demographic data is now available for 162 patients in the neoadjuvant arm: 89% male; median age 64 years (range, 37–78); 45% PS 0; 53% squamous cell, 27% adenocarcinoma, 13% large cell; 7% stage IA, 64% IB, 2% IIA, 24% IIB, 2.5% T3N1. Neoadjuvant chemotherapy has been well tolerated with a median number of cycles per patient of 3. No unexpected toxicities have been seen with 12% of patients having grade 3–4 neutropenia and 43% grade 1–2 anemia. Major radiographic response has been observed in 59% of patients and progression during chemotherapy occurred in 6%. No patient characteristics were predictive for clinical response. Resection procedures at thoracotomy: lobectomy or bilobectomy in 70%, pneumonectomy in 26%, and explorative thoracotomy due to unresectable disease in 3% of patients. Post-operative mortality was 4%. Median tumor size was 4.5 cm at baseline CT-scan and 2.5 cm at surgery. At surgery, 9% patients had pathologic complete response, 75% N0–1 disease (with persistent T tumor), and 15% pathologic N2 disease. Conclusion: Neoadjuvant chemotherapy in early NSCLC has proven feasible and safe in this large multicenter sample. Chemotherapy compliance has been high and resectability rates as expected. Our findings are comparable with those of previous studies (BLOT and S9900). Mature survival results of the NATCH trial are expected in 2009. No significant financial relationships to disclose.

Risk Factors for Occult Mediastinal Metastases in Clinical Stage I Non-Small Cell Lung Cancer

In patients deemed to have clinical stage I for non-small cell lung cancer (NSCLC) after computerized tomography (CT) and positron emission tomography (PET) scans, the utility of mediastinoscopy to detect occult mediastinal metastases is unclear. The goal of this study was to analyze the risk factors for occult mediastinal metastases in this subset of patients. We conducted a retrospective review during a 7-year period to identify patients with potentially operable clinical stage I NSCLC screened by CT and PET scans. Medical records were reviewed, and the prevalence of pathologic N2 disease was analyzed according to clinical tumor location, size, histology, and PET uptake of the primary tumor. Of 224 patients identified with clinical stage I NSCLC with a CT-negative and PET-negative mediastinum, 16 patients had pathologic N2 disease proven by mediastinoscopy (n = 11) or after resection (n = 5). The overall prevalence of histologically confirmed N2 disease was 6.5% in clinical T1 patients and 8.7% in clinical T2 patients. Central tumors had a higher prevalence of N2 disease compared with peripheral tumors, 21.6% versus 2.9% (p < 0.001). Larger clinical T size predicted a higher prevalence of occult N2 disease (p < 0.001). All 16 patients with occult N2 metastases had adenocarcinoma as the primary tumor cell type. When the PET maximum standardized uptake value (SUV(max)) of the primary tumors was analyzed, patients with occult N2 metastases had a higher median SUV(max) of the primary tumor compared with patients without N2 metastases, 6.0 g/mL versus 3.6 g/mL (p = 0.017). For patients deemed at clinical stage I NSCLC by CT and PET, the prevalence of missed N2 metastases increased significantly with larger tumor size and central location. Adenocarcinoma cell type and a high PET SUV(max) of the primary tumor were other risk factors. Mediastinoscopy may have improved yield in the select subset of patients with one or more risk factor.

Case-control study between extrapleural pneumonectomy and radical pleurectomy/decortication for pathological N2 malignant pleural mesothelioma☆

To compare the outcomes of extrapleural pneumonectomy (EPP) and radical pleurectomy/decortication (P/D) for N2 malignant pleural mesothelioma (MM). In a retrospective case-control study we analysed the results of the 57 patients [49 male and 8 female, median age 59 (range 14-70) years] who underwent radical surgery for MM found to have pathological N2 disease over a 7-year-period. EPP was performed on 45 and P/D on 12 patients. Prognostic factors, postoperative course, pathological data and postoperative survival were analysed. Those in the P/D group were significantly older (median age 62 vs 58 years, p=0.03) than in the EPP group. There was no difference in postoperative hospital stay (p=0.1) nor T stage (p=0.7) between the groups. There were no significant differences in the proportion of patients undergoing some adjuvant therapy in each group (p=0.2). Mean survival from diagnosis was 15 months in the EPP group and 16 months for those who underwent P/D (p=0.4). Preservation of the lung during radical surgery for N2 MM does not compromise survival even in an older group population. We therefore now have ceased to perform EPP in cases of N2 disease and we make every effort to accurately stage patients with mediastinoscopy to identify them.

Superior Vena Cava Resection for Lung and Mediastinal Malignancies: A Single-Center Experience With 70 Cases

The oncologic value of superior vena cava (SVC) resection for lung and mediastinal malignancies remains controversial. In this context, we have reviewed our experience in the treatment of locally advanced lung and mediastinal tumor invading the SVC system, analyzing postoperative outcome and long-term oncologic results. The clinical data of patients who underwent SVC resection were retrospectively analyzed to assess postoperative mortality, and overall and procedure-specific morbidity. Overall survival was calculated for mediastinal and lung tumor groups. From 1998 to 2004, 70 consecutive patients (52 with lung cancer and 18 with mediastinal tumors) underwent SVC system resection. There were 25 replacements (36%) of the SVC system by prosthesis, whereas the remaining underwent partial resection. Major postoperative morbidity and mortality rates in lung cancer patients were 23% and 7.7%, respectively (50% and 5.6% in mediastinal tumors). In the lung cancer group, 5-year survival probability was 31%, and it was affected by mediastinal nodal status (5-year survival in N0-N1 patients 52%, 21% in N2 patients, 0 in N3 patients). Median survival for mediastinal tumors was 49 months. In conclusion, SVC resection may achieve permanent cure in patients who would have been defined as inoperable 10 years ago. In the case of mediastinal tumors, the need for SVC resection alone should not be considered a contraindication for surgery when prosthetic replacement is feasible. In the case of lung tumors, infiltration of SVC can achieve satisfactory long-term results after neoadjuvant chemotherapy, only when pathologic N2 disease is excluded by preoperative mediastinoscopy.

Size of Metastatic and Nonmetastatic Mediastinal Lymph Nodes in Non-small Cell Lung Cancer

To determine the optimum selection of mediastinal lymph nodes for biopsy in non-small cell lung cancer (NSCLC), lymph nodes with or without metastasis at each mediastinal station were ranked in size in patients with pathological N2 disease. Twenty-five NSCLC patients with pathological N2 disease who underwent pulmonary resection with complete mediastinal lymph node clearance were examined. Of 114 mediastinal lymph node stations dissected, 47 had metastases and 67 did not. The sizes of 259 nodes in the 47 positive lymph node stations were measured. Of these 259 nodes, 137 had metastases and 122 did not. The short- and long-axis diameters of the 259 lymph nodes were ranked in each lymph node station. Mean short- and long-axis diameters of lymph nodes with metastases were significantly greater than those without (p < 0.001). In 47 metastatic lymph node stations, the short- and long-axis diameters were greatest in a metastatic node in 44 (94%) and 42 (89%) respectively, whereas in the remaining 3 (6%) and 5 (11%), the second largest but not the largest node was positive. None of the largest lymph nodes with metastasis were smaller than the second largest lymph node at each station. Four of the 10 patients with adenocarcinoma (40%) had metastasis in the second largest but not in the largest node measured by long-axis diameter, a significant difference from one in eight (12.5%) among the squamous cell carcinoma cases (p = 0.04). For mediastinal lymph node biopsy, both the largest and the second largest node at each station should be sampled, especially in adenocarcinoma. If only the largest lymph node is selected, false-negative results will occur at a rate of about 10%.

Salvage neck dissections in oral and oropharyngeal squamous cell carcinoma: histological features in relation to disease category

The histological findings in a series of 37 salvage neck dissections from patients who had an oral or oropharyngeal squamous cell carcinoma managed initially by primary surgery with or without neck dissection, and without postoperative radiotherapy, are described. None of the cases had an intraoral relapse. Pathological stage N2 or N3 disease was seen in 87% of the 15 salvage dissections from ‘wait and watch’ necks, 100% of the 10 salvage dissections of contralateral necks and 50% of the 12 salvage dissections of operated necks. The typical ‘inverted-cone’ pattern of metastasis was seen in 87% of ‘wait and watch’ necks. Skip or non-contiguous metastases to level III/IV accounted for relapse in 30% of the contralateral and 66% of the operated necks. The median time interval between original surgery and the salvage neck dissection was 15 months (range 1–48 months). In at least 15% of cases, the short time interval coupled with the histopathological features suggested that the metastatic disease suddenly became more rapidly progressive following removal of the primary tumour.

Surgical resection for lung cancer with infiltration of the thoracic aorta

The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Prognostic significance of surgical-pathologic multiple-station N1 disease in non-small cell carcinoma of the lung.

The surgical outcome of pathologic N1 disease in resectable non-small cell lung carcinoma (NSCLC) is controversial. The prognosis of the patients with multiple/bulky N2 disease was invariably dismal. However, the prognostic significance of tumor involvement in more than one hilar or intralobar lymph node station has not been fully described. From 1996 to 2002, 181 patients with NSCLC had complete resection. Four levels of N1 nodes and N2 nodes were identified using the new regional lymph node classification for lung cancer staging. There were 67 patients (37%) with no nodal disease (N0), 43 patients (24%) with N1 and 71 patients (39%) with N2 disease. The N1 subgroup cases were reviewed. The prognostic significances of single and multiple N1 diseases were tested. The cumulative postoperative survival at 3 and 5 years was 57 and 29%, respectively. The survival associated with single-station N1 disease was significantly better than that of multiple-station N1 disease (45 vs 32% at 5 years; P=0.03). Five-year survival was similar in patients with multiple N1 disease and patients with single-station N2 involvement (32 vs 31% at 5 years; P=0.84). However, no patient survived when tumor was detected in more than one mediastinal station (i.e. multiple N2 disease). It was suggested that N1 disease is a compound of two subgroups: one involving in one node and the other (multiple N1 disease) in which the postoperative prognosis was not statistically different from that of N2 disease.

Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer.

N1 non-small cell lung cancer (NSCLC) encompasses a heterogeneous subgroup with differential lymph node involvement. Among 738 patients with NSCLC who underwent surgical resection, including 579 patients (78.5%) with systematic hilar and mediastinal lymph nodal dissection, from 1992 to 2001, 82 patients were pathologically defined as having N1 disease. We retrospectively analyzed the factors influencing survival, including the characteristics of lymph node involvement; the location of involved stations, the number of involved stations, the number of involved nodes, and the status of nodal involvement (microscopic N1, nodal involvement first defined by postoperative histological examination; or macroscopic N1, nodal involvement obviously recognized by preoperative examinations or surgical explorations). The overall 5-year survival rate of the 82 patients with N1 disease was 50.9%. No significant differences in the overall survival were found with regard to gender, age, histologic type, type of resection, or adjuvant therapies. Pathologic T status significantly influenced the overall survival (T1 versus T2 disease, P=0.008). According to the characteristics of lymph node involvement, the prognosis of patients with multiple-node N1 involvement was significantly poorer than that of those with single-node N1 involvement (5-year survival: 29.6% versus 61.5%, p=0.003). The prognosis of patients with macroscopic N1 disease was significantly poorer than that of those with microscopic N1 disease (5-year survival: 43.0% versus 65.0%, P=0.046). By comparison with the survival of patients who underwent surgical resection during the same period for pathologic N0 (pN0) and pathologic N2 (pN2) diseases, no survival differences were observed between microscopic N1/single-node N1 and pN0, or between multiple-node N1 and pN2 diseases. In patients with pathologic N1 disease, microscopic N1 and single-node N1 diseases may be an early stage, whereas multiple-node N1 disease behaves like an advanced stage.

The impact of residual multi-level N2 disease after induction therapy for non-small cell lung cancer

Background: The presence of residual N2 disease following induction therapy for locally advanced non-small cell lung cancer (NSCLC) has been proposed as a contraindication to surgery. However, single level N2 metastases found in the operative specimens of patients with clinical N0 NSCLC who did not receive induction therapy is associated with prolonged survival. In order to investigate whether residual single level N2 disease following induction therapy was similarly associated with prolonged survival, we conducted a retrospective review of patients with stages IIIa and IIIb NSCLC who had undergone induction therapy followed by surgery. Methods: A retrospective review was performed of the hospital records of patients with stages IIIa and IIIb NSCLC who had undergone induction therapy consisting of chemotherapy and/or radiotherapy followed by tumor resection and mediastinal lymph node dissection at 11 Japanese national referral hospitals. Survival was analyzed by the Kaplan–Meier method and prognostic factors were determined by the log-rank and Cox regression methods. Results: One hundred thirty-one patients underwent induction therapy of NSCLC stages IIIa (n=95) and IIIb (n=36) followed by complete tumor resection during a 12-year interval. Clinical N2 disease was present in 114 (87%) patients and N3 disease in 17 (13%) patients. Median follow up was 48 months. Eighteen patients had residual single level N2 disease and 25 patients had multiple residual N2 level metastases. The 5-year survival was 54% for patients with pathologic single level N2 disease and 11% for patients with multiple N2 level disease ( P<0.01). In a multivariate analysis, only the pathologic N status significantly influenced survival. Conclusion: Patents who have multiple levels of N2 disease have a much worse prognosis than patients who have single level of N2.

Recurrence-free survival and prognostic factors in resected pN2 non-small cell lung cancer.

We sought to evaluate recurrence pattern and prognostic factors of recurrence-free survival in surgically resected N2 non-small cell lung cancer. Between September 1994 and December 1999, 564 patients underwent operation for non-small cell lung cancer at our institute. Of these 564 patients, 101 patients were found to have pathologic N2 disease. Systematic mediastinal lymph node dissection was performed in all these patients. Recurrence was determined and nineteen clinicopathologic prognostic factors were evaluated in relation to recurrence-free survival. Complete resection rate was 83.2% and overall 5-year survival was 23.3%. Locoregional and distant metastasis were detected in 50 of 101 patients (49.5%) during follow-up. Five-year recurrence-free survival was 19.6%. Among 19 clinicopathologic prognostic factors, incomplete resection and non-downstaging after neoadjuvant therapy were unfavorable prognostic factors in univariate analyses. Clinical N2 status, multiple N2 nodes, and cell type of adenocarcinoma showed poor prognosis but were not statistically significant. Postoperative chemotherapy showed good prognosis but was not statistically significant. Multivariate analysis showed that significant favorable prognostic factors were complete resection and adjuvant chemotherapy. Complete resection and responsiveness to neoadjuvant therapy were the most important favorable prognostic factors in recurrence-free survival. Postoperative chemotherapy was also a favorable prognostic factor but not statistically significant in recurrence-free survival in pN2 non-small cell lung cancer.