Characteristics and prognosis of resected T3 non-small cell lung cancer

BACKGROUND: T3 tumors can be divided into several subgroups depending on the type of anatomical structure invaded: chest wall, mediastinal pleura, or main bronchus. The aim of this study was to analyze the characteristics and prognosis of each subgroup of T3 tumors. METHODS: The results of surgical treatment were retrospectively analyzed for 261 patients with T3 non-small cell lung cancer invading either the mediastinal pleura or parietal pericardium by direct extension (mediastinal pT3, n = 68), or main bronchus (bronchial pT3, n = 68), or chest wall (chest wall pT3, n = 125) that were operated on between 1984 and 1996. Complete resection including radical mediastinal lymph node dissection was intended in all patients. One patient had segmentectomy, 91 had lobectomy (34.9%), and 169 had pneumonectomy (64.8%). One hundred and fifty-eight patients received adjuvant radiation therapy and 7 patients received both adjuvant chemotherapy and radiation therapy. Actuarial survival curves were drawn using the Kaplan-Meier method and risk factors for late death were identified. RESULTS: In-hospital mortality was 6.1%. Follow-up was 98% complete. Global 5-year survival was 28%, with survival being not significantly different among the three subgroups: 34.9%, 30.6%, and 22.5% (p = 0.19) in the bronchial pT3, mediastinal pT3, and chest wall pT3 subgroups, respectively. Resection margins were microscopically invaded in 33 patients (12.6%). Seventy-four patients had N1 involvement (28.4%) and 78 patients had N2 involvement (29.8%). N0 involvement was more prevalent in the chest wall pT3 subgroup, whereas N1 involvement was more prevalent in the bronchial pT3 subgroup and N2 involvement was more prevalent among patients with mediastinal invasion. Pathologic factors influencing the 5-year survival were tumor size (p = 0.03) and N involvement (p = 0.003). Histology, type of surgical resection (lobectomy versus pneumonectomy), and use of adjuvant therapy did not influence survival significantly. CONCLUSIONS: Five-year survival was not significantly different among the three subgroups of pT3 non-small cell lung cancer, although bronchial pT3 tumors tended to have a better prognosis and chest wall pT3 tumors tended to have a worse prognosis. The pathologic characteristics of each pT3 subgroup seems different. Further research is warranted to explore the pathologic and biological factors influencing prognosis for each pT3 subgroup.     

Survival and prognostic factors of surgically resected T4 non-small cell lung cancer

BACKGROUND: Category T4 nonsmall cell lung cancer (NSCLC) encompasses heterogenous subgroups. We retrospectively analyzed the survival of patients with surgically resected T4 NSCLC to evaluate the evidence for prognostic implications according to the subgroups of T4 category, nodal status, and resection completeness. METHODS: Seventy-six patients with T4N0-2M0 NSCLC were divided into three subgroups within the T4 category: 24 patients with the tumor invading the mediastinal organs (mediastinal group), 16 with a malignant pleural effusion or dissemination (pleural group), and 36 with satellite tumor nodules within the ipsilateral primary tumor lobe (satellite group). Complete resection was possible in 47 patients (61.8%). The pathologic N statuses were N0 in 28, N1 in 13, and N2 in 35 patients. RESULTS: The overall survival of the 76 patients was 19.1% at 5 years. The overall 5-year survivals according to the three subgroups of the T4 category were as follows: mediastinal group, 18.2%; pleural group, 0%; and satellite group, 26.7% (mediastinal/satellite versus pleural, p = 0.037). Factors significantly influencing the overall 5-year survival were the pathologic N status (N2 versus N0-1, p = 0.022) and the completeness of resection (complete versus incomplete, p = 0.0001). A multivariate survival analysis demonstrated that the pathologic N status and the completeness of resection were significant independent predictors of a poorer prognosis even after adjusting for the subgroup of the T4 category. CONCLUSIONS: Resectable T4N0-1 NSCLC that is not due to pleural disease deserves consideration of aggressive surgical resection with expected 5-year survival of about 20%.     

手术切除的T4卫星灶非小细胞肺癌的预后分析

目的 研究手术治疗后T4卫星灶非小细胞肺癌的生存和预后.方法 回顾性分析1995年1月至2005年3月经手术切除的42例T4卫星灶N0-2M0非小细胞肺癌患者的术后生存情况,评价各临床病理因素与预后的关系,并与同期32例手术切除的T4局部器官侵犯N0-2M0的非小细胞肺癌进行生存比较.结果 T4卫星灶组无手术死亡,术后早期并发症率为14.3%,1、3、5年生存率分别为76.2%、57.1%和46.0%;T4局部器官侵犯组术后早期并发症率为28.1%,1、3、5年生存率分别为62.3%、31.5%和20.0%;两组生存率有明显差异(P<0.05).根据淋巴结转移情况进一步分组,两组中N0M0患者的生存率均高于同组的N1-2M0患者(P<0.05).单因素分析显示,组织学类型、原发灶大小、有无淋巴结转移及是否术后辅助化疗与T4卫星灶患者的5年生存率相关;多因素分析显示原发灶大小、有无淋巴结转移及是否接受术后化疗是独立的预后影响因素.结论 原发灶直径3 cm、淋巴结转移以及未接受术后化疗的T4卫星灶非小细胞肺癌预后不佳,经手术完全切除的T4卫星灶非小细胞肺癌的预后好于T4局部器官侵犯者.     

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.     

外科治疗ⅢA期N2非小细胞肺癌的预后分析及临床意义

目的 探讨影响ⅢA期N2非小细胞肺癌（NSCLC）预后的因素，并分析经手术治疗不同亚组病人的生存率差异。方法 分析1997年1月至2000年1月146例手术治疗的ⅢA期N2 NSCLC病人的可能影响预后因素：病理类型、肿瘤位置、肿瘤大小、手术方式、临床N2情况，N2转移组数及个数、术后辅助治疗等，并用Kaplan-Meier曲线及Logr ank检验生存率差异，Cox单因素、多因素分析各因素对生存率的影响。结果 ⅢA期N2 NSCLC病人的3年和5年生存率分别为19．86％和14．56％。单因素分析示肿瘤位置、临床N2情况、N2转移组数及个数是影响生存率的因素；多因素分析示肿瘤大小、临床N2情况，N2转移组数和肿瘤位置影响预后。右肺下叶肿瘤单组或单个N2转移，预后最好。结论 纵隔N2转移淋巴结的大小、个数和组数是影响术后生存率主要因素。手术前未发现N2转移（mN2），有1组N2转移（N2h），N2转移数少于4个者手术治疗效果好。右肺下叶肿瘤发生单组N2淋巴结转移预后好。     

Adjuvant chemotherapy for surgically resected non-small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.     

Locally advanced non-small cell lung cancer completely resected after induction therapy

We analyzed 8 patients with unresectable locally advanced non-small cell lung cancer who responded to chemotherapy or chemoradiotherapy and underwent complete resection between June 2003 and June 2005. The patients were all male with a mean age of 61 years (range, 42 to 72 years). Histological subtypes included adenocarcinoma in 4 patients and squamous cell carcinoma in 4 patients. Clinical staging included T2N2M0 in 3 patients, T2N3M0 in 2 patients, and 1 patient each for T3N2M0, T4N2M0, and T4N3M0. Preoperative treatment included chemotherapy in 5 patients and chemoradiotherapy in 3 patients, all of whom had a partial response. Surgical procedures included lobectomy in 6 patients and pneumonectomy in 2 patients. In addition, all of the patients underwent mediastinal lymph node dissection (ND2a). Pathological effect included Ef. 0 in 1 patient, Ef. 1 in 2 patients, Ef. 2 in 2 patients, Ef. 3 in 3 patients. The median survival time from initial treatment (or surgery) was 16 (14) months in all cases, 22 (19) for ycN0, 12 (8) for ycN2, 31 (27) for Ef. 3, 13 (9) for Ef. 0-2, 27 (23) for pN0, 13 (9) for pN1-3, 31 (27) for chemoradiotherapy, 16 (13) for chemotherapy, 24 (21) for adenocarcinoma, and 15 (11) for squamous cell carcinoma. Multimodality treatment, including surgery, is beneficial for patients with unresectable locally advanced non-small cell lung cancer who respond to chemotherapy or chemoradiotherapy, especially those patients with ycN0 or pN0.     

Multifocal T4 non-small cell lung cancer: a subset with improved prognosis.

OBJECTIVE: T4-disease for non-small cell lung cancer (NSCLC) includes different conditions: mediastinal invasion, neoplastic pleural cytology, and multifocal disease in the same lobe; regarding the last category, no strict criteria allow to differentiate satellite nodules from synchronous multiple primary tumours. METHODS: Retrospective study of 56 patients who underwent a complete resection from 1985 to 2006 of a NSCLC graded pT4N0 due to multifocal disease. A small nodule (<1cm) closed to the primary tumour, in a same pulmonary segment with an identical histology was considered as a satellite nodule (pT4sn). Multiple tumours, sized more than 1cm, with an identical histology, located in the same lobe but in different segment were considered as synchronous cancers (pT4sc). RESULTS: There were 44 males and 12 females: 35 patients were graded T4sn and 21 patients T4sc. The median age was 62.5 years. The two groups were similar for sex, age, tobacco consumption, ASA score, NYHA, Charlson's index, spirometric parameters, cardiovascular comorbidity and history of previous extra-thoracic malignancies. All had a complete anatomic resection with mediastinal lymphadenectomy. Thirty-day mortality rate was 3.6%. Overall 5-year and 10-year survival rates were 48.2% and 29.9%, respectively. There was a non-significant trend for a worse survival in T4sn group patients when compared to that of T4sc group patients: 42.9% vs 52.3% at 5 years, and 25% vs 34.9% at 10 years (p=0.62). CONCLUSIONS: Multifocal T4 stage IIIB disease is a heterogeneous category where overall prognosis is far better than those of other T4 subgroups. Survival rates associated with pT4sn and pT4sc look roughly similar because of the small size of the subgroups usually submitted to comparison in most series. In the present experience, respective survival figures diverge, suggesting different biological behaviours.     

手术切除T4期肺癌的疗效分析

目的 探讨外科手术切除侵犯心脏、大血管和气管隆凸的T4期肺癌的预后和手术适应证。方法回顾性总结1988至2000年手术切除的151例T4期肺癌（心脏大血管成形术130例，隆凸成形术21例）病人资料，对可能影响其生存率的各种临床、病理、治疗等因素进行分析，并与同期112例手术切除的T3N1M0肺癌病人进行预后比较。结果全组无手术死亡病例，术后并发症发生率为43％。术后中位生存时间26．1个月，1年、3年、5年生存率分别为73．5％、33．1％和16．6％。单因素分析表明，病人预后与年龄、肺切除范围、有无淋巴结转移、是否根治性切除及是否行新辅助化疗有关（P〈0．05）。多因素分析结果表明，肺切除范围、有无淋巴结转移、是否根治性切除是影响总生存率的独立预后因素（P〈0．05）。T4N0M0与同期T3N1M0病人5年生存率分别为38．6％、16．1％，两组比较差异有统计学意义（P=0．0383），而术后并发症发生率差异无统计学意义（P〉0．05）。结论对于侵犯心脏、大血管和隆凸的T4期肺癌，正确选择病例和良好的手术技术确保完整切除局部肿瘤，也能取得较满意的临床疗效。尤其是对以局部浸润为主而无淋巴结转移的T4期肺癌，手术疗效优于有淋巴结转移的，13期肺癌。新辅助化疗有助于延长术后生存期。     

Risk factors of recurrence in resected stage I non-small cell lung cancer

We reviewed risk factors of recurrence in resected pathological stage I non-small cell lung cancer (I NSCLC). Objective is 229 complete resected I NSCLC in our department. Risk factors of recurrence were carcinoembryonic antigen (CEA), histology, differentiation, lymphatic invasion, blood vessel invasion, pleural invasion and tumor size. By univariate analysis, lymphatic invasion (p=0.009), blood vessel invasion (p=0.008), pleural invasion, p1 (p=0.013), p2 (p=0.001), and tumor size (value of cut off was 2 cm) were significant risk factors of recurrence. By multivariate analysis, blood vessel invasion (p=0.004), pleural invasion (p1 or p2) [p=0.001], were significantly risk factors of recurrence. It was suggested that I NSCLC presenting pathological blood vessel invasion and/or pleural invasion should be recognized as cases with a high risk of recurrence, and a strict follow-up and adjuvant therapy should be in consideration.     

Cytologically malignant margins of wedge resected stage I non-small cell lung cancer

BACKGROUND: We have developed a novel test for the surgical margin of pulmonary malignant tumor using a cytologic technique (the run-across method in which a glass slide is run across the staple site), and we have assessed whether this method is useful in predicting margin relapse and prognosis. METHODS: From April 1996 to March 1999, 15 lesions of stage I non-small cell lung cancer (NSCLC) (maximum diameter ranged from 10 to 35 mm with a median of 20 mm) from 15 patients with cardiopulmonary impairment were excised without additional proximal resections. The surgical margin was examined using the run-across method. There were 8 male 7 female patients whose ages ranged from 51 to 80 years. One patient underwent video-assisted thoracic surgery and 14 underwent thoracotomy. The preoperative diagnoses of the patients were 13 adenocarcinomas, 2 squamous cell carcinomas, and 1 undiagnosed lesion (1 adenocarcinoma). The follow-up period ranged from 37 to 63 months. RESULTS: The rate of positive cytology was 47% in comparison with the rate of positive histology of 20%. There were 4 patients with margin relapse (3 of them contained negative histology margins) at a rate of 57% among the positive cytology patients in comparison with 0% among the negative cytology patients (p = 0.03). In a comparison of survival between the negative cytology group and the positive cytology group, there were no statistically significant differences. CONCLUSIONS: The run-across method is also useful in confirming complete resection. A positive cytology margin could lead to margin relapse even if a non-small cell lung cancer is resected with a negative histology margin.     

The prognosis of surgically resected N2 non-small cell lung cancer: the importance of clinical N status.

BACKGROUND: Clinical trials dealing with multimodal strategy for N2 non-small cell lung cancer are now being watched with keen interest, and the feasibility of this strategy is to be confirmed. N2 lung cancer, however, is composed of several subgroups with different prognoses. The prognostic factors still remain controversial. METHODS: Between January 1986 and July 1997, 222 patients with lung cancer underwent surgical intervention at our institute; these patients were eventually given a diagnosis of metastasis to ipsilateral mediastinal lymph nodes. All patients underwent mediastinal lymph node dissection or sampling. Sixteen clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Clinical N status was evaluated by computed tomographic scan. RESULTS: The overall 5-year survival was 27%. Multivariable analyses among overall patients revealed 4 significant prognostic factors (P <.05): clinical N2 status, incomplete resection, larger tumor size, and multiple diseased N2 nodes. Based on the result, 32 patients with both clinical N2 status and pathologic multiple N2 nodes showed a 5-year survival of 5%, whereas 76 patients with neither of the factors showed a 5-year survival of 57% (P <.001). CONCLUSION: The prognosis of surgically resected N2 disease varies tremendously according to the 4 significant prognostic factors. These factors should be clearly described in reporting clinical trials on N2 lung cancer. Clinical N status evaluated by computed tomographic scan should be 1 criterion to perform a clinical trial for N2 disease among a homogeneous population with respect to prognosis.     

Prognostic value of the histological subtype in completely resected non-small cell lung cancer

Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.     

Results of surgical treatment of patients with T3 non-small cell lung cancer

Sixty-one patients with T3 non-small cell lung cancer were surgically treated in our department from February, 1974, through April, 1986. The overall 5-year survival, excluding patients with pleurisy, was 23%, and the 5-year survival for patients undergoing complete resection and incomplete resection was 42% and 10%, respectively (p less than 0.01). Survival in patients with T3 N0 and T3 N1 or N2 disease was 33% and 0 at 5 years, respectively. The prognosis for patients with pleurisy was poor, and all died within 3 years. Therefore, complete lung resection should be done in patients with T3 N0 non-small cell lung cancer if complete resection is expected. Long-term survival is less likely for patients with lymph node metastases if complete resection cannot be performed.     

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

OBJECTIVE: We sought to evaluate recurrence pattern and prognostic factors of recurrence-free survival in surgically resected N2 non-small cell lung cancer. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.