Tumor Biol. (2014) 35:5905–5910 DOI 10.1007/s13277-014-1781-8
RESEARCH ARTICLE
Reevaluation of survival and prognostic factors in pathologic stage I lung adenocarcinoma by the new 2009 TNM classification Xiaohong Fan & Xueyan Zhang & Huimin Wang & Bo Jin
Received: 18 January 2014 / Accepted: 19 February 2014 / Published online: 23 March 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract The incidence of lung adenocarcinoma has been increased significantly year by year. In this histologic type, complete surgical resection is commonly chosen as treatment method at the initial stages. However, the postoperative survival rate remains unsatisfactory even within the stage I. The purpose of this study is to investigate the factors related with prognosis in stage I lung adenocarcinoma after surgical resection. In this manuscript, a retrospective study was performed. Survival rates were calculated by the Kaplan-Meier method, and for multivariate analyses, Cox proportional hazards regression model was used. The results indicated that a total of 531 patients were included. Overall 5-year survival was 81.2 %. Age, sex, pathologic stage, T category, tumor size, differentiation, necrosis, visceral pleural invasion (VPI), lymphatic vessel or vascular invasion, and serum carcinoembryonic antigen (CEA) were significantly associated with 5-year overall survival of the patients with Kaplan-Meier analysis. Moreover, on multivariate analyses, seven variables were shown to be independent prognostic factors, including differentiation (hazard ratios (HR), 1.357), VPI (HR, 0.551), lymphatic vessel or vascular invasion (HR, 0.533), necrosis (HR, 1.671), age (HR, 1.519), pathological stage (HR, 4.477), and CEA (HR, 2.099). In conclusion, the most important prognostic factor is pathologic stage. Other adverse prognostic factors include differentiation, VPI, lymphatic vessel or vascular invasion, necrosis, age, and CEA.
Keywords Lung adenocarcinoma . Prognostic factor . Pathologic stage I disease . TNM staging X. Fan (*) : X. Zhang : H. Wang : B. Jin Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, People’s Republic of China e-mail: [email protected]
Introduction Lung cancer is the most lethal disease worldwide due to its high incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80 % of lung cancers [1]. In recent years, the incidence of lung adenocarcinoma has increased significantly and has become the most prevalent subtype of NSCLC. Furthermore, the long-term survival rate of patients with lung adenocarcinoma remains unsatisfactory. Thus, there is an urgent need for more understandings of the NSCLC progression, especially for lung adenocarcinoma [2]. In this histologic type, complete surgical resection is commonly chosen as treatment method at the initial stages; however, the postoperative survival rate remains unsatisfactory even within the stage I. It is unknown, however, what mechanisms result in these recurrences or in what kind of patients they will occur. We sought to explore the prognostic significance of this classification in a large group of patients with surgically resected stage I lung adenocarcinomas. The identification of prognostic factors in lung cancer is very useful for assessing the individual patient prognosis, selecting the best treatment, defining new criteria to classify patients according to risk groups and helping design and guide future research [3]. There are a variety of clinical and pathologic factors that could be associated with prognosis of patients with lung adenocarcinoma, such as disease stage, age, gender, tumor size, lymph node and metastatic status, and tumor differentiation [4]. Among them, the “tumor, node, and metastasis” (TNM) staging system is widely used by oncologists to estimate prognosis and choose the most suitable therapy [5]. In 2009, the UICC and the AJCC published the seventh edition of the TNM classification for malignant tumors, which was applied to the clinical field and from January 2010 to nowadays. In this edition, the lung cancer classification, which has incorporated important modifications, was updated by the International Staging Committee of the IASLC [6].
5906
Therefore, the objectives of this study are to validate our surgical series of patients with pathologic stage I lung adenocarcinoma according to the seventh edition of the TNM classification and clarify the factors associated with poor prognosis.
Tumor Biol. (2014) 35:5905–5910
primary antibodies used consisted of rat monoclonal antihuman carcinoembryonic antigen (CEA) (1:200, Santa Cruz, USA), and the secondary antibodies were purchased from DAKO company, USA. Survival and prognostic factors analysis
Materials and methods Patients We performed a retrospective study, analyzing survival and determining prognostic factors. We retrospectively reviewed the records of 531 consecutive patients, admitted from June 1998 to June 2007, with a confirmed pathologic stage I lung adenocarcinoma, who had undergone radical resection and lymph node dissection at Shanghai Chest Hospital. Among these 531 cases, 314 were male and 217 were female. Patients’ age at the time of surgery ranged from 22 to 81 years (median age, 57). The patients had not received either adjuvant or induction treatment. This study was approved by the ethics committee of Shanghai Jiaotong University. All of the patients have given their consents for this study. Tumor classification Surgical-pathologic staging was carried out according to the seventh edition of TNM Classification of Malignant Tumors by the International Association for the Study of Lung Cancer (IASCLC). Histopathological studies were conducted according to the World Health Organization criteria. Lung adenocarcinoma was divided into three degrees of differentiation, including well, moderately, and poorly differentiated. Surgical operation In all patients, complete surgical resection was performed. Lobectomy was considered as the standard lung resection. Atypical lung resection was done in patients with high surgical risk or poor cardiorespiratory reserve. Usually, lymphadenectomy was performed systematically after lung resection. This study was conducted under the regulations of the Institutional Review Board. All patients were successfully followed up for at least 5 years after operation. Immunohistochemistry of CEA The samples were fixed in 10 % formaldehyde, dehydrated with ethanol, and then embedded in paraffin. Serial sections were cut at 2-μm intervals and were collected sequentially onto glass slides coated with poly-L-lysine. The sections were deparaffinized with xylene and rehydrated in graded ethanol. Then the section were stained using the EnVision method. The
For the analysis of the survival and prognostic factors, the following variables were selected, including age, sex, pathologic stage, T category, resection type, tumor size, degree of differentiation, necrosis, visceral pleural invasion, lymphatic vessel or vascular invasion and CEA. The statistical analysis was carried out with SPSS 11.0 software package for Windows. Statistical analysis Overall survival was estimated using the Kaplan-Meier method, and any differences in survival were determined by the log-rank analysis. Zero time was the date of pulmonary resection, and the end point was defined as the date of death. The last follow-up observation was censored when the patient was alive or lost to follow-up. A multivariate analysis was performed to determine the independent prognostic values of the statistically significant univariate factors by Cox proportional hazard model. A P value less than 0.05 was considered statistically significant.
Results Clinic pathologic characteristics Clinicopathological characteristics of patients were shown in Table 1. A total of 531 patients with stage I lung adenocarcinoma were studied. There were 314 men and 217 women. Their age ranged from 22 to 81 with a mean age of 57 years. Lung-conservation surgery, such as lobectomy, was performed in 490 cases (92.3 %), and atypical resection in 41 cases (7.7 %). Diagnosis of p-stage IA disease was made in 265 patients (49.9 %), and diagnosis of p-stage IB was made in 266 patients (50.1 %), with a ratio about 1:1. The tumor size was classified into three categories, including tumors between 0 and 2 cm, tumors between 2.1 and 3 cm, and tumors between 3.1 and 5 cm, with 286 (53.9 %), 132 (24.8 %), and 113 (21.3 %) patients, respectively. A total of 212 patients (39.9 %) had a tumor with pathologically proven pleural invasion. Vascular or Lymphatic vessel invasion was found in 39 patients (7.3 %). The WHO histological grade (2004 edition) was well, moderate, and poorly differentiated in 167 (31.5 %), 243 (45.8 %), and 121 (22.8 %) of cases, respectively. Necrosis and CEA elevated were seen in 67 (12.6 %) and 67 (12.6 %) of the cases, respectively.
Tumor Biol. (2014) 35:5905–5910
5907
Table 1 five-year survival analysis according to the Kaplan-Meier method (n=531)
Age ≥60
RESEARCH ARTICLE
Reevaluation of survival and prognostic factors in pathologic stage I lung adenocarcinoma by the new 2009 TNM classification Xiaohong Fan & Xueyan Zhang & Huimin Wang & Bo Jin
Received: 18 January 2014 / Accepted: 19 February 2014 / Published online: 23 March 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
Abstract The incidence of lung adenocarcinoma has been increased significantly year by year. In this histologic type, complete surgical resection is commonly chosen as treatment method at the initial stages. However, the postoperative survival rate remains unsatisfactory even within the stage I. The purpose of this study is to investigate the factors related with prognosis in stage I lung adenocarcinoma after surgical resection. In this manuscript, a retrospective study was performed. Survival rates were calculated by the Kaplan-Meier method, and for multivariate analyses, Cox proportional hazards regression model was used. The results indicated that a total of 531 patients were included. Overall 5-year survival was 81.2 %. Age, sex, pathologic stage, T category, tumor size, differentiation, necrosis, visceral pleural invasion (VPI), lymphatic vessel or vascular invasion, and serum carcinoembryonic antigen (CEA) were significantly associated with 5-year overall survival of the patients with Kaplan-Meier analysis. Moreover, on multivariate analyses, seven variables were shown to be independent prognostic factors, including differentiation (hazard ratios (HR), 1.357), VPI (HR, 0.551), lymphatic vessel or vascular invasion (HR, 0.533), necrosis (HR, 1.671), age (HR, 1.519), pathological stage (HR, 4.477), and CEA (HR, 2.099). In conclusion, the most important prognostic factor is pathologic stage. Other adverse prognostic factors include differentiation, VPI, lymphatic vessel or vascular invasion, necrosis, age, and CEA.
Keywords Lung adenocarcinoma . Prognostic factor . Pathologic stage I disease . TNM staging X. Fan (*) : X. Zhang : H. Wang : B. Jin Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, People’s Republic of China e-mail: [email protected]
Introduction Lung cancer is the most lethal disease worldwide due to its high incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80 % of lung cancers [1]. In recent years, the incidence of lung adenocarcinoma has increased significantly and has become the most prevalent subtype of NSCLC. Furthermore, the long-term survival rate of patients with lung adenocarcinoma remains unsatisfactory. Thus, there is an urgent need for more understandings of the NSCLC progression, especially for lung adenocarcinoma [2]. In this histologic type, complete surgical resection is commonly chosen as treatment method at the initial stages; however, the postoperative survival rate remains unsatisfactory even within the stage I. It is unknown, however, what mechanisms result in these recurrences or in what kind of patients they will occur. We sought to explore the prognostic significance of this classification in a large group of patients with surgically resected stage I lung adenocarcinomas. The identification of prognostic factors in lung cancer is very useful for assessing the individual patient prognosis, selecting the best treatment, defining new criteria to classify patients according to risk groups and helping design and guide future research [3]. There are a variety of clinical and pathologic factors that could be associated with prognosis of patients with lung adenocarcinoma, such as disease stage, age, gender, tumor size, lymph node and metastatic status, and tumor differentiation [4]. Among them, the “tumor, node, and metastasis” (TNM) staging system is widely used by oncologists to estimate prognosis and choose the most suitable therapy [5]. In 2009, the UICC and the AJCC published the seventh edition of the TNM classification for malignant tumors, which was applied to the clinical field and from January 2010 to nowadays. In this edition, the lung cancer classification, which has incorporated important modifications, was updated by the International Staging Committee of the IASLC [6].
5906
Therefore, the objectives of this study are to validate our surgical series of patients with pathologic stage I lung adenocarcinoma according to the seventh edition of the TNM classification and clarify the factors associated with poor prognosis.
Tumor Biol. (2014) 35:5905–5910
primary antibodies used consisted of rat monoclonal antihuman carcinoembryonic antigen (CEA) (1:200, Santa Cruz, USA), and the secondary antibodies were purchased from DAKO company, USA. Survival and prognostic factors analysis
Materials and methods Patients We performed a retrospective study, analyzing survival and determining prognostic factors. We retrospectively reviewed the records of 531 consecutive patients, admitted from June 1998 to June 2007, with a confirmed pathologic stage I lung adenocarcinoma, who had undergone radical resection and lymph node dissection at Shanghai Chest Hospital. Among these 531 cases, 314 were male and 217 were female. Patients’ age at the time of surgery ranged from 22 to 81 years (median age, 57). The patients had not received either adjuvant or induction treatment. This study was approved by the ethics committee of Shanghai Jiaotong University. All of the patients have given their consents for this study. Tumor classification Surgical-pathologic staging was carried out according to the seventh edition of TNM Classification of Malignant Tumors by the International Association for the Study of Lung Cancer (IASCLC). Histopathological studies were conducted according to the World Health Organization criteria. Lung adenocarcinoma was divided into three degrees of differentiation, including well, moderately, and poorly differentiated. Surgical operation In all patients, complete surgical resection was performed. Lobectomy was considered as the standard lung resection. Atypical lung resection was done in patients with high surgical risk or poor cardiorespiratory reserve. Usually, lymphadenectomy was performed systematically after lung resection. This study was conducted under the regulations of the Institutional Review Board. All patients were successfully followed up for at least 5 years after operation. Immunohistochemistry of CEA The samples were fixed in 10 % formaldehyde, dehydrated with ethanol, and then embedded in paraffin. Serial sections were cut at 2-μm intervals and were collected sequentially onto glass slides coated with poly-L-lysine. The sections were deparaffinized with xylene and rehydrated in graded ethanol. Then the section were stained using the EnVision method. The
For the analysis of the survival and prognostic factors, the following variables were selected, including age, sex, pathologic stage, T category, resection type, tumor size, degree of differentiation, necrosis, visceral pleural invasion, lymphatic vessel or vascular invasion and CEA. The statistical analysis was carried out with SPSS 11.0 software package for Windows. Statistical analysis Overall survival was estimated using the Kaplan-Meier method, and any differences in survival were determined by the log-rank analysis. Zero time was the date of pulmonary resection, and the end point was defined as the date of death. The last follow-up observation was censored when the patient was alive or lost to follow-up. A multivariate analysis was performed to determine the independent prognostic values of the statistically significant univariate factors by Cox proportional hazard model. A P value less than 0.05 was considered statistically significant.
Results Clinic pathologic characteristics Clinicopathological characteristics of patients were shown in Table 1. A total of 531 patients with stage I lung adenocarcinoma were studied. There were 314 men and 217 women. Their age ranged from 22 to 81 with a mean age of 57 years. Lung-conservation surgery, such as lobectomy, was performed in 490 cases (92.3 %), and atypical resection in 41 cases (7.7 %). Diagnosis of p-stage IA disease was made in 265 patients (49.9 %), and diagnosis of p-stage IB was made in 266 patients (50.1 %), with a ratio about 1:1. The tumor size was classified into three categories, including tumors between 0 and 2 cm, tumors between 2.1 and 3 cm, and tumors between 3.1 and 5 cm, with 286 (53.9 %), 132 (24.8 %), and 113 (21.3 %) patients, respectively. A total of 212 patients (39.9 %) had a tumor with pathologically proven pleural invasion. Vascular or Lymphatic vessel invasion was found in 39 patients (7.3 %). The WHO histological grade (2004 edition) was well, moderate, and poorly differentiated in 167 (31.5 %), 243 (45.8 %), and 121 (22.8 %) of cases, respectively. Necrosis and CEA elevated were seen in 67 (12.6 %) and 67 (12.6 %) of the cases, respectively.
Tumor Biol. (2014) 35:5905–5910
5907
Table 1 five-year survival analysis according to the Kaplan-Meier method (n=531)
Age ≥60
![[New TNM classification of lung tumors].](/assets/img/hold.png)
