Is T2 non-small cell lung cancer located in left lower lobe appropriate to upstage
http://www.100md.com
《血管的通路杂志》
Second Department of Surgery, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Abstract
In the TNM classification, patients with T2 non-small cell lung cancer (NSCLC) have heterogeneous factors. The efficacy of surgery for T2 disease remains unsatisfactory. We retrospectively reviewed 268 T2 patients with non-small cell lung cancer for whom a curative approach had been attempted between January 1994 through December 2003. All patients were subjected to lobectomy, including dissection of hilar and mediastinal lymph nodes contained in pathologically proven adenocarcinoma or squamous cell carcinoma. The overall survival rates at 5 and 7 years were 58.4% and 48.5%, respectively. Five-year survival of patients with a tumor in the left lower lobe (LLL) was 38.8%; other lobe, 61.6%. Primary tumor distribution in the LLL was significantly associated with a poor survival in T2 NSCLC. In univariate analysis, tumors size less than 4 cm, tumor in the left lower lobe, histological differentiation, lymph node involvement were significantly associated with prognosis. Multivariate analysis showed that tumor in the left lower lobe (P=0.0159), histological differentiation (P=0.0071), and lymph node involvement (P=0.0266) were found to be independent prognostic factors in cases of T2 disease. In cases where the primary tumor without well differentiation is in the LLL, surgery for T2 NSCLC should be considered carefully.
Key Words: T2 NSCLC; Left lower lobe; Histological differentiation
1. Introduction
T2 non-small cell lung cancer (NSCLC) is a heterogeneous cancer subgroup, characterized according to tumor diameter, invasion of visceral pleura, associated atelectasis, and extension of the tumor into the bronchus. The characteristics of T2 NSCLC patients are relatively wide, and this variety is reflected in wide differences in survival rates after complete resection. The treatment modality for patients with T2 NSCLC suffering from a large or from the presence of nodes remains somewhat controversial due to the heterogeneous characteristics of patients afflicted with this disease. Carbone et al. reported that a tumor size of more than 5 cm in diameter indicated a poor prognosis in non-small cell lung cancer, and that in such cases T2 might be upgraded to T3 or higher [1]. Watanabe et al. reported that the 5-year survival rate of patients with T2, even T2N0M0, ranged from 61.0% to 46.3% [2]. Cancer extension beyond the elastic layer but without exposure on the pleural surface (p1) was classified as T2. Shimizu et al. showed that tumors of sizes greater than 3 cm with visceral pleural invasion should be upgraded to T3 status in the International Union Against Cancer TNM classification [3]. Furthermore, Kang and colleagues demonstrated that visceral pleural invasion was a factor in the poor prognosis of T2 NSCLC [4]. Recently, some authors presented that the sub-groups of N2 disease with single-station or skip metastasis have a more favorable prognosis than other groups [5,6]. And several studies showed that the frequency of skip metastasis was higher in patients with the primary tumor in the upper rather than lower lobe [7]. These data suggested that the prognosis of T2 NSCLC might be influenced by the tumor distribution of the lobe, especially in the lower lobe. Therefore, the aims of this study were to investigate these clinical evaluations of patients with T2 NSCLC and attempt to clarify the factors affecting prognosis. The significance of indications for surgical resection for T2 patients are also discussed.
2. Patients and methods
From January 1994 to December 2003, 890 patients underwent pulmonary surgical resection for NSCLC at Fukuoka University Hospital. Among these, we retrospectively selected 268 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of non-small cell carcinoma (NSCLC) with T2, all of whom had received a complete resection and had been considered to be potentially cured by the surgical approach. To eliminate the influence of heterogeneity in the surgical approach (pneumonectomy, wedge resection, segmentectomy, lobectomy), all of these patients were subjected to lobectomy with mediastinal lymphadenectomy. The routine follow-up of these patients after surgery consisted of clinical evaluations performed every month. All tumors were staged post-operatively according to the classification system of the Internal Union Against Cancer (UICC). The cutoff of tumor size was 4 cm, which showed the average diameter (3.97±1.76) of tumors in this study.
Statistical analysis: All statistical analyses were performed with the StatView software package (StatView 5.0, SAS Institute Inc.). Survival rates were calculated by the Kaplan–Meier method, while survival curves were compared using a log-rank test. For multivariate analysis, a Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. In all statistical analysis, significance was defined as P value less than 0.05.
3. Results
3.1. Patient characteristics
Table 1 summarizes the 268 patients. Their mean age was 66.75±10.13 years. Histologically, there were 168 adenocarcinomas and 100 squamous cell carcinomas. And there were 168 well differentiation and 100 without-well (moderately or poorly) differentiation. The postoperative pathological N status included 175 patients at N0, 93 at node involvement (N1,27; N2, 66). Of the 27 patients with N1 metastasis, 13 were hilar and 14 were inter-lobar metastasis. Among the 66 patients with N2 disease of this study, 20 (30.3%) had single station. There were 143 tumors with a maximum diameter of 4 cm or less and 125 with a maximum diameter of more than 4 cm. Of all 268 who received a lobecttomy, 20 patients had bronchoplasty. The primary tumors were located as follows: right upper lobe, 85; right middle lobe, 56; right lower lobe, 17; left upper lobe, 74; left lower lobe, 36.
3.2. Relationship between each factor and prognosis
The actual survival rates are shown in Fig. 1. The overall survival rate was 58.4% at 5 years and 48.5% at 7 years. The 5-year survival rate for patients at p-N0 was 68.2%, the rate for cases at node involvement was 39.1% (N1, 57.2%; N2, 32.7%, respectively). The 7-year survival rates for these groups were 56.4% and 32.8%, respectively. Statistically significant difference is between various cases, all of whom have lymph node invasion (P=0.0001). The 5-year survival rate of patients with tumors less than 4 cm in diameter was 65.8%, vs. 51.7% for patients with tumors of more than 4 cm. The corresponding 7-year survival rates were 58.8% vs. 37.5%. Survival rates differed significantly between patients with tumors of less than 4 cm and those with tumors of more than 4 cm (P=0.0022). We further analyzed the survival rates of the patients to identify any correlations between survival and each primary tumor site in T2 disease.
The 5-year survival of patients (n=36) whose tumors were in the left lower lobe was 38.8%, vs. 61.6% for patients (n=212) with tumors in the other lobe. The corresponding 7-year survival rates were 19.4% and 52.4% (Fig. 2). A statistically significant association was found in survival rates between left lower and other lobe tumors (P=0.0237).
The results of univariate analysis are summarized in Table 2, histological differentiation (P=0.0018), lymph node involvement (P=0.0001), tumor size (P=0.0435), primary tumor site (P=0.0258) were significantly associated with prognosis. Otherwise, gender, age, histology, pleural invasion had not shown significance factors.
Multivariate analysis evaluated the independent prognostic role of each of these factors in all of the cases. All variables that significantly affected survival were part of an analysis using the Cox proportional hazards model (Table 3). At the end of the stepwise process, tumor without well differentiation (P=0.0071, hazard ratio=1.889) and without nodal involvement (P=0.0266, hazard ratio=0.470), and LLL location (P=0.0159, hazard ratio=2.013) displayed an independent prognostic influence on overall survival.
4. Discussion
In general, pathologic T status significantly influenced the overall survival rate. In TNM staging, peripheral tumors greater than 3 cm diameter are classified as T2. Our T2 group was divided into two groups according to the tumor dimension: a cutoff of 4 cm was identified. There was a significant difference in the survival rate between patients with a tumor of less than 4 cm vs. those with a tumor of greater than 4 cm in diameter (P=0.0022). Although the size of 4 cm was not found as an independent factor in multivariate analysis, these results suggested that T2 tumors greater than 4 cm may be upgraded to at least T3. Watanabe et al. suggested that T2N0M0 should be divided into two groups according to a 5-cm cutoff, which delineates a significant difference in survival rates: the 5-year survival rate was 61% for tumors of less than 5 cm and 46.3% for those more than 5 cm [8]. Lafitte et al., based on their own data from administering radiation to treat T2N0M0 NSCLC, suggested that stage I T2N0M0 non-small cell lung carcinoma tends to manifest itself in distant metastasis [9]. In this group, adjuvant therapy should also be pursued and radical resection will improve the prognosis. This finding may support our suggestion that T2 tumors larger than 4 cm should be upgraded and may require additional therapy after surgery. But Velzen et al. demonstrated that survival was not related to tumor size or surgical procedure, that patients with metastatic invasion of the lobar lymph node have significantly better prognoses than do patients with other types in T2N1M0 disease [10]. Recently, Osaki and associates reported that the prognoses of patients with p1 were significantly poorer than those with p0 for tumors of any size above 3 cm (5-year survival: 46.1% vs. 69.6%) [11]. But our data showed that visceral pleural invasion did not statistically appear to play an important role in the prognosis of T2 NSCLC.
In addition, the possible prognostic significance of location was also analyzed in T2 NSCLC. As shown in Fig. 2, the 5-year survival rate was 38.8% in patients whose primary tumor was located in the left lower lobe, 61.6% in the other lobe. In T2 cases, location in the left lower lobe significantly affected the survival rate. This result suggested that the lymphatic channel may differ between the left lower lobe and the other lobes. A similar trend was observed in patients with completely resected stage IIIA NSCLC [12]. Rocha et al. demonstrated that the location of a primary tumor in a lower lobe was the only statistically significant factor associated with upgrading and deserves special attention [13]. In some reports, lower lobe tumors spread to the subcarinal station more frequently than upper lobe tumors did [14]. A previous report showed that the rate of skip metastasis was 5–15% in NSCLC and 20–40% in N2 disease cases [15]. Moreover, several studies showed that the frequency of skip metastasis was higher in patients whose primary tumor was in an upper rather than lower lobe [7]. Our data may be suggesting that the lymph channels of the left lower lobe into the mediastinum occur with greater frequency than they do in the other lobes, and further contralateral nodal clean-out for LLL NSCLC should be recommended. Otherwise, when a primary tumor is distributed in the right lower lobe, the lymphatic spread may be blocked by the structure of the middle lobe. This should be considered carefully when choosing the type of surgery for a tumor located in the lower left lobe; indeed the tumor might be upgraded above stage T2 in NSCLC.
In the multivariate analysis of the complete resections for our 286 patients with T2, histological differentiation, tumor location, and nodal involvement were each shown to be a significant predictor of survival. The tumor without-well (moderately or poorly) differentiation which have the character invasive and progression well known to poorer than well differentiation. This finding may explain the possibility which tumor with poorer differentiation in located LLL easily spread wide and it associated with poor survival in T2. In T2 cases showing some of these factors adjuvant chemotherapy may be indicated or careful follow-up may be necessary.
In conclusion, each of several relevant factors (tumor location, histological differentiation, and node status) must be considered in formulating a surgical approach to lung cancer cases with T2 tumors.
References
Carbone E, Asamura H, Takei H, Kondo H, Suzuki K, Miyaoka E, Tsuchiya R, Motta G. T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer. J Thorac Cardiovasc Surg 2001;122:907–912.
Watanabe Y, Shimizu J, Oda M, Hayashi Y, Iwa T, Nonomura A, Kamimura R, Takashima T. Proposal regarding some deficiencies in the new international staging system for non-small cell lung cancer. Jpn J Clin Oncol 1991;21:160–168.
Shimizu K, Yoshida J, Nagai K, Nishimura M, Yokose T, Ishii G, Nishiwaki Y. Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment. J Thorac Cardiovasc Surg 2004;127:1574–1578.
Kang JH, Kim KD, Chung KY. Prognostic value of visceral pleura invasion in non-small cell lung cancer. Eur J Cardiothorac Surg 2003;23:865–869.
Keller SM, Vangel MG, Wagner H, Schiller JH, Herskovic A, Komaki R, Marks RS, Perry MC, Livingston RB, Johnson DH. Eastern Cooperative Oncology Group. Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease. J Thorac Cardiovasc Surg 2004;128:130–137.
Misthos P, Sepsas E, Athanassiadi K, Kakaris S, Skottis I. Skip metastases: analysis of their clinical significance and prognosis in the IIIA stage of non-small cell lung cancer. Eur J Cardiothorac Surg 2004;25:502–508.
Inoue M, Sawabata N, Takeda S, Ohta M, Ohno Y, Maeda H. Results of surgical intervention for p-stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe. J Thorac Cardiovasc Surg 2004;127:1100–1106.
Watanabe Y, Shimizu J, Oda M, Hayashi Y, Iwa T, Nonomura A. Proposal regarding some deficiencies in the New International Staging System for non-small cell lung cancer. Jpn J Clin Oncol 1991;21:160–168.
Lafitte JJ, Ribet ME, Prevost BM, Gosselin BH, Copin MC, Brichet AH. Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study. Ann Thorac Surg 1996;62:830–304.
van Velzen E, Snijder RJ, Brutel de la Riviere A, Elbers HR, van den Bosch JM. Lymph node type as a prognostic factor for survival in T2 N1 M0 non-small cell lung carcinoma. Ann Thorac Surg 1997;63:1436–1440.
Osaki T, Nagashima A, Yoshimatsu T, Tashima Y, Yasumoto K. Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer 2004;43:151–157.
Ichinose Y, Kato H, Koike T, Tsuchiya R, Fujisawa T, Shimizu N, Watanabe Y, Mitsudomi T, Yoshimura M, Tsuboi M. Japanese Clinical Oncology Group. Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station. J Thorac Cardiovasc Surg 2001;122:803–808.
Rocha AT, McCormack M, Montana G, Schreiber G. Association between lower lobe location and upstaging for early-stage non-small cell lung cancer. Chest 2004;125:1424–1430.
. Canadian Lung Oncology Group. Investigation for mediastinal disease in patients with apparently operable lung cancer. Ann Thorac Surg 1995;60:1382–1389.
Prenzel KL, Monig SP, Sinning JM, Baldus SE, Gustshow CA, Grass G, Schneider PM, Holscher AH. Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer. J Surg Oncol 2003;82:256–260.(Akinori Iwasaki, Takayuki)
Abstract
In the TNM classification, patients with T2 non-small cell lung cancer (NSCLC) have heterogeneous factors. The efficacy of surgery for T2 disease remains unsatisfactory. We retrospectively reviewed 268 T2 patients with non-small cell lung cancer for whom a curative approach had been attempted between January 1994 through December 2003. All patients were subjected to lobectomy, including dissection of hilar and mediastinal lymph nodes contained in pathologically proven adenocarcinoma or squamous cell carcinoma. The overall survival rates at 5 and 7 years were 58.4% and 48.5%, respectively. Five-year survival of patients with a tumor in the left lower lobe (LLL) was 38.8%; other lobe, 61.6%. Primary tumor distribution in the LLL was significantly associated with a poor survival in T2 NSCLC. In univariate analysis, tumors size less than 4 cm, tumor in the left lower lobe, histological differentiation, lymph node involvement were significantly associated with prognosis. Multivariate analysis showed that tumor in the left lower lobe (P=0.0159), histological differentiation (P=0.0071), and lymph node involvement (P=0.0266) were found to be independent prognostic factors in cases of T2 disease. In cases where the primary tumor without well differentiation is in the LLL, surgery for T2 NSCLC should be considered carefully.
Key Words: T2 NSCLC; Left lower lobe; Histological differentiation
1. Introduction
T2 non-small cell lung cancer (NSCLC) is a heterogeneous cancer subgroup, characterized according to tumor diameter, invasion of visceral pleura, associated atelectasis, and extension of the tumor into the bronchus. The characteristics of T2 NSCLC patients are relatively wide, and this variety is reflected in wide differences in survival rates after complete resection. The treatment modality for patients with T2 NSCLC suffering from a large or from the presence of nodes remains somewhat controversial due to the heterogeneous characteristics of patients afflicted with this disease. Carbone et al. reported that a tumor size of more than 5 cm in diameter indicated a poor prognosis in non-small cell lung cancer, and that in such cases T2 might be upgraded to T3 or higher [1]. Watanabe et al. reported that the 5-year survival rate of patients with T2, even T2N0M0, ranged from 61.0% to 46.3% [2]. Cancer extension beyond the elastic layer but without exposure on the pleural surface (p1) was classified as T2. Shimizu et al. showed that tumors of sizes greater than 3 cm with visceral pleural invasion should be upgraded to T3 status in the International Union Against Cancer TNM classification [3]. Furthermore, Kang and colleagues demonstrated that visceral pleural invasion was a factor in the poor prognosis of T2 NSCLC [4]. Recently, some authors presented that the sub-groups of N2 disease with single-station or skip metastasis have a more favorable prognosis than other groups [5,6]. And several studies showed that the frequency of skip metastasis was higher in patients with the primary tumor in the upper rather than lower lobe [7]. These data suggested that the prognosis of T2 NSCLC might be influenced by the tumor distribution of the lobe, especially in the lower lobe. Therefore, the aims of this study were to investigate these clinical evaluations of patients with T2 NSCLC and attempt to clarify the factors affecting prognosis. The significance of indications for surgical resection for T2 patients are also discussed.
2. Patients and methods
From January 1994 to December 2003, 890 patients underwent pulmonary surgical resection for NSCLC at Fukuoka University Hospital. Among these, we retrospectively selected 268 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of non-small cell carcinoma (NSCLC) with T2, all of whom had received a complete resection and had been considered to be potentially cured by the surgical approach. To eliminate the influence of heterogeneity in the surgical approach (pneumonectomy, wedge resection, segmentectomy, lobectomy), all of these patients were subjected to lobectomy with mediastinal lymphadenectomy. The routine follow-up of these patients after surgery consisted of clinical evaluations performed every month. All tumors were staged post-operatively according to the classification system of the Internal Union Against Cancer (UICC). The cutoff of tumor size was 4 cm, which showed the average diameter (3.97±1.76) of tumors in this study.
Statistical analysis: All statistical analyses were performed with the StatView software package (StatView 5.0, SAS Institute Inc.). Survival rates were calculated by the Kaplan–Meier method, while survival curves were compared using a log-rank test. For multivariate analysis, a Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. In all statistical analysis, significance was defined as P value less than 0.05.
3. Results
3.1. Patient characteristics
Table 1 summarizes the 268 patients. Their mean age was 66.75±10.13 years. Histologically, there were 168 adenocarcinomas and 100 squamous cell carcinomas. And there were 168 well differentiation and 100 without-well (moderately or poorly) differentiation. The postoperative pathological N status included 175 patients at N0, 93 at node involvement (N1,27; N2, 66). Of the 27 patients with N1 metastasis, 13 were hilar and 14 were inter-lobar metastasis. Among the 66 patients with N2 disease of this study, 20 (30.3%) had single station. There were 143 tumors with a maximum diameter of 4 cm or less and 125 with a maximum diameter of more than 4 cm. Of all 268 who received a lobecttomy, 20 patients had bronchoplasty. The primary tumors were located as follows: right upper lobe, 85; right middle lobe, 56; right lower lobe, 17; left upper lobe, 74; left lower lobe, 36.
3.2. Relationship between each factor and prognosis
The actual survival rates are shown in Fig. 1. The overall survival rate was 58.4% at 5 years and 48.5% at 7 years. The 5-year survival rate for patients at p-N0 was 68.2%, the rate for cases at node involvement was 39.1% (N1, 57.2%; N2, 32.7%, respectively). The 7-year survival rates for these groups were 56.4% and 32.8%, respectively. Statistically significant difference is between various cases, all of whom have lymph node invasion (P=0.0001). The 5-year survival rate of patients with tumors less than 4 cm in diameter was 65.8%, vs. 51.7% for patients with tumors of more than 4 cm. The corresponding 7-year survival rates were 58.8% vs. 37.5%. Survival rates differed significantly between patients with tumors of less than 4 cm and those with tumors of more than 4 cm (P=0.0022). We further analyzed the survival rates of the patients to identify any correlations between survival and each primary tumor site in T2 disease.
The 5-year survival of patients (n=36) whose tumors were in the left lower lobe was 38.8%, vs. 61.6% for patients (n=212) with tumors in the other lobe. The corresponding 7-year survival rates were 19.4% and 52.4% (Fig. 2). A statistically significant association was found in survival rates between left lower and other lobe tumors (P=0.0237).
The results of univariate analysis are summarized in Table 2, histological differentiation (P=0.0018), lymph node involvement (P=0.0001), tumor size (P=0.0435), primary tumor site (P=0.0258) were significantly associated with prognosis. Otherwise, gender, age, histology, pleural invasion had not shown significance factors.
Multivariate analysis evaluated the independent prognostic role of each of these factors in all of the cases. All variables that significantly affected survival were part of an analysis using the Cox proportional hazards model (Table 3). At the end of the stepwise process, tumor without well differentiation (P=0.0071, hazard ratio=1.889) and without nodal involvement (P=0.0266, hazard ratio=0.470), and LLL location (P=0.0159, hazard ratio=2.013) displayed an independent prognostic influence on overall survival.
4. Discussion
In general, pathologic T status significantly influenced the overall survival rate. In TNM staging, peripheral tumors greater than 3 cm diameter are classified as T2. Our T2 group was divided into two groups according to the tumor dimension: a cutoff of 4 cm was identified. There was a significant difference in the survival rate between patients with a tumor of less than 4 cm vs. those with a tumor of greater than 4 cm in diameter (P=0.0022). Although the size of 4 cm was not found as an independent factor in multivariate analysis, these results suggested that T2 tumors greater than 4 cm may be upgraded to at least T3. Watanabe et al. suggested that T2N0M0 should be divided into two groups according to a 5-cm cutoff, which delineates a significant difference in survival rates: the 5-year survival rate was 61% for tumors of less than 5 cm and 46.3% for those more than 5 cm [8]. Lafitte et al., based on their own data from administering radiation to treat T2N0M0 NSCLC, suggested that stage I T2N0M0 non-small cell lung carcinoma tends to manifest itself in distant metastasis [9]. In this group, adjuvant therapy should also be pursued and radical resection will improve the prognosis. This finding may support our suggestion that T2 tumors larger than 4 cm should be upgraded and may require additional therapy after surgery. But Velzen et al. demonstrated that survival was not related to tumor size or surgical procedure, that patients with metastatic invasion of the lobar lymph node have significantly better prognoses than do patients with other types in T2N1M0 disease [10]. Recently, Osaki and associates reported that the prognoses of patients with p1 were significantly poorer than those with p0 for tumors of any size above 3 cm (5-year survival: 46.1% vs. 69.6%) [11]. But our data showed that visceral pleural invasion did not statistically appear to play an important role in the prognosis of T2 NSCLC.
In addition, the possible prognostic significance of location was also analyzed in T2 NSCLC. As shown in Fig. 2, the 5-year survival rate was 38.8% in patients whose primary tumor was located in the left lower lobe, 61.6% in the other lobe. In T2 cases, location in the left lower lobe significantly affected the survival rate. This result suggested that the lymphatic channel may differ between the left lower lobe and the other lobes. A similar trend was observed in patients with completely resected stage IIIA NSCLC [12]. Rocha et al. demonstrated that the location of a primary tumor in a lower lobe was the only statistically significant factor associated with upgrading and deserves special attention [13]. In some reports, lower lobe tumors spread to the subcarinal station more frequently than upper lobe tumors did [14]. A previous report showed that the rate of skip metastasis was 5–15% in NSCLC and 20–40% in N2 disease cases [15]. Moreover, several studies showed that the frequency of skip metastasis was higher in patients whose primary tumor was in an upper rather than lower lobe [7]. Our data may be suggesting that the lymph channels of the left lower lobe into the mediastinum occur with greater frequency than they do in the other lobes, and further contralateral nodal clean-out for LLL NSCLC should be recommended. Otherwise, when a primary tumor is distributed in the right lower lobe, the lymphatic spread may be blocked by the structure of the middle lobe. This should be considered carefully when choosing the type of surgery for a tumor located in the lower left lobe; indeed the tumor might be upgraded above stage T2 in NSCLC.
In the multivariate analysis of the complete resections for our 286 patients with T2, histological differentiation, tumor location, and nodal involvement were each shown to be a significant predictor of survival. The tumor without-well (moderately or poorly) differentiation which have the character invasive and progression well known to poorer than well differentiation. This finding may explain the possibility which tumor with poorer differentiation in located LLL easily spread wide and it associated with poor survival in T2. In T2 cases showing some of these factors adjuvant chemotherapy may be indicated or careful follow-up may be necessary.
In conclusion, each of several relevant factors (tumor location, histological differentiation, and node status) must be considered in formulating a surgical approach to lung cancer cases with T2 tumors.
References
Carbone E, Asamura H, Takei H, Kondo H, Suzuki K, Miyaoka E, Tsuchiya R, Motta G. T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer. J Thorac Cardiovasc Surg 2001;122:907–912.
Watanabe Y, Shimizu J, Oda M, Hayashi Y, Iwa T, Nonomura A, Kamimura R, Takashima T. Proposal regarding some deficiencies in the new international staging system for non-small cell lung cancer. Jpn J Clin Oncol 1991;21:160–168.
Shimizu K, Yoshida J, Nagai K, Nishimura M, Yokose T, Ishii G, Nishiwaki Y. Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment. J Thorac Cardiovasc Surg 2004;127:1574–1578.
Kang JH, Kim KD, Chung KY. Prognostic value of visceral pleura invasion in non-small cell lung cancer. Eur J Cardiothorac Surg 2003;23:865–869.
Keller SM, Vangel MG, Wagner H, Schiller JH, Herskovic A, Komaki R, Marks RS, Perry MC, Livingston RB, Johnson DH. Eastern Cooperative Oncology Group. Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease. J Thorac Cardiovasc Surg 2004;128:130–137.
Misthos P, Sepsas E, Athanassiadi K, Kakaris S, Skottis I. Skip metastases: analysis of their clinical significance and prognosis in the IIIA stage of non-small cell lung cancer. Eur J Cardiothorac Surg 2004;25:502–508.
Inoue M, Sawabata N, Takeda S, Ohta M, Ohno Y, Maeda H. Results of surgical intervention for p-stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe. J Thorac Cardiovasc Surg 2004;127:1100–1106.
Watanabe Y, Shimizu J, Oda M, Hayashi Y, Iwa T, Nonomura A. Proposal regarding some deficiencies in the New International Staging System for non-small cell lung cancer. Jpn J Clin Oncol 1991;21:160–168.
Lafitte JJ, Ribet ME, Prevost BM, Gosselin BH, Copin MC, Brichet AH. Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study. Ann Thorac Surg 1996;62:830–304.
van Velzen E, Snijder RJ, Brutel de la Riviere A, Elbers HR, van den Bosch JM. Lymph node type as a prognostic factor for survival in T2 N1 M0 non-small cell lung carcinoma. Ann Thorac Surg 1997;63:1436–1440.
Osaki T, Nagashima A, Yoshimatsu T, Tashima Y, Yasumoto K. Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer 2004;43:151–157.
Ichinose Y, Kato H, Koike T, Tsuchiya R, Fujisawa T, Shimizu N, Watanabe Y, Mitsudomi T, Yoshimura M, Tsuboi M. Japanese Clinical Oncology Group. Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station. J Thorac Cardiovasc Surg 2001;122:803–808.
Rocha AT, McCormack M, Montana G, Schreiber G. Association between lower lobe location and upstaging for early-stage non-small cell lung cancer. Chest 2004;125:1424–1430.
. Canadian Lung Oncology Group. Investigation for mediastinal disease in patients with apparently operable lung cancer. Ann Thorac Surg 1995;60:1382–1389.
Prenzel KL, Monig SP, Sinning JM, Baldus SE, Gustshow CA, Grass G, Schneider PM, Holscher AH. Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer. J Surg Oncol 2003;82:256–260.(Akinori Iwasaki, Takayuki)