Clinicopathologic analysis of small-sized non-small cell lung cancer

We reviewed the data on 149 patients who underwent complete resection for small-sized (≤ 2 cm)peripheral non-small cell lung cancer at our institution between January 2002 and July 2010. Patients with small-sized lung cancer underwent a lobectomy in 121, segmentectomy in 13, and wedge resection in 15 cases. The overall and 5-year disease-free survivals were 89% and 82%, respectively. The 5-year disease-free survival of patients with tumors exceeding 1.5 cm was lower than that of patients with tumors 1.5 cm or smaller (p=0.01). The 5-year disease-free survival for patients without pleulal invasion was 87%, whereas it was 45% for those with pleulal invasion (p=0.004). The 5-year disease-free survival according to the serum level of carcinoembrionic antigen( CEA) were 82% for the normal group and 70% for the high group( p=0.007). Although the results were not significantly different, patients with tumors with high maximum standardized uptake value (SUV) on FDG-PET/CT showed a trend toward a lower 5-year disease-free survival rate( p=0.10). There were no recurrences in patients with ground-glass opacity (GGO) or GGO-dominant lesion including those who underwent sublober resection. Multivariate analysis showed that tumor size and pleural invasion were independent prognostic factors. Indication of sublober resection for solid-type small-sized non-small cell lung cancer (NSCLC) should be carefully determined considering tumor size, pleural involvement, serum carcinoembryonic antigen( CEA) level, and maximum SUV.     

The prognostic value of carcinoembryonic antigen in T1N1M0 and T2N1M0 non-small cell carcinoma of the lung.

OBJECTIVE: To evaluate the significance of preoperative clinicopathological factors, including serum carcinoembryonic antigen (CEA), as well as postoperative clinicopathological factors in T1-2N1M0 patients with non-small cell lung cancer who underwent curative pulmonary resection. METHODS: Twenty T1N1M0 disease patients and 25 T2N1M0 patients underwent standard surgical procedures between September 1996 and December 2005, and were found to have non-small lung cancer. As prognostic factors, we retrospectively investigated age, sex, Brinkman index, histologic type, primary site, tumor diameter, clinical T factor, clinical N factor, pathological T factor, preoperative serum CEA levels, surgical procedure, visceral pleural involvement, and the status of lymph node involvement (level and number). RESULTS: The overall 5-year survival rate of all patients was 59.6%. In univariate analysis, survival was related to age (<70/>or=70 years, p=0.0079), site (peripheral/central, p=0.043), and CEA level (<5.0/>or=5.0 ng/ml, p=0.0015). However, in multivariate analysis, CEA (<5.0/>or=5.0 ng/ml) was the only independent prognostic factor; the 5-year survival of the patients with an elevated serum CEA level (>or=5.0 ng/ml) was only 33.2% compared to 79.9% in patients with a lower serum CEA level (<5.0 ng/ml). CONCLUSIONS: An elevated serum CEA level (>or=5.0 ng/ml) was an independent predictor of survival in pN1 patients except for T3 and T4 cases. Therefore, even in completely resected pN1 non-small cell lung cancer, patients with a high CEA level might be candidates for multimodal therapy.     

Pleural lavage cytology in non-small cell lung cancer: lessons from 1000 consecutive resections

OBJECTIVE: Intraoperative pleural lavage cytology for lung cancer has not been widely accepted. The prognostic significance of this procedure has yet to be intensively analyzed because the reports published thus far have involved small patient populations. We therefore performed a large prospective trial of pleural lavage cytology to elucidate its importance. METHODS: Cytologic status of pleural lavage fluid before any manipulation of the lung was examined in 1000 consecutive patients with non-small cell lung cancer but no pleural effusion who underwent tumor resection. RESULTS: Forty-five (4.5%) of 1000 patients had positive cytologic findings. Positive cytologic findings were observed more frequently in patients with adenocarcinoma, advanced stage, higher involvement of lymph nodes, pleural involvement of the tumor, lymphatic permeation, vascular invasion, high level of serum carcinoembryonic antigen, and male sex. The survival rate for 5 years was 28% in patients with positive findings and 67% in patients with negative findings (P <.0001). Among 587 patients with stage I disease, 13 (2.2%) had positive findings, and their 5-year survival was 43%, which was significantly poor compared with that of patients with negative findings (81%, P =.0009). Multivariable analysis demonstrated that pleural lavage cytology was an independent prognostic determinant (P =.0290). Regarding the recurrence pattern in patients with positive findings, distant metastases (19/45 [42.2%]) were observed more frequently rather than local recurrences (19/45 [22.2%]). CONCLUSIONS: Cytologic status of pleural lavage fluid immediately after thoracotomy, an independent significant prognostic factor, constitutes valuable information to detect patients at a high risk of recurrence. Therefore cytology should be performed at the time of curative resection for non-small cell lung cancer.     

Simple preoperative computed tomography image analysis shows good predictive performance for pathological vessel invasion in clinical stage IA non-small cell lung cancer

OBJECTIVES Pathological vessel invasion is a well-known prognostic factor in early-stage, non-small cell lung cancer and preoperative predicting vessel invasion may enable us to improve prognosis by additional interventions. We evaluated the importance of vessel invasion as a prognostic factor in clinical stage IA non-small cell lung cancer and predictive performance of simple diameter-based computed tomography image analysis for vessel invasion. METHODS The study design was retrospective, and we reviewed 398 patients who underwent surgical resection of clinical stage IA non-small cell lung cancer from 1999 to 2009. The prognostic factors for recurrence-free survival were examined by univariate and multivariate analyses. Additionally, we analyzed preoperative high-resolution computed tomography images of patients with adenocarcinoma. The greatest diameter of the tumor in the lung window and the length of the consolidation part of L in the mediastinal window were measured. Then the ratio (mediastinal window/lung window) was calculated, and the correlation between the ratio (mediastinal window/lung window) and vessel invasion was analyzed by receiver operating characteristic analysis. RESULTS Sixty-eight recurrences occurred. Multivariate analysis revealed that vessel invasion, high preoperative serum carcinoembryonic antigen, and history of other malignancy were independent prognostic factors; their hazard ratios were 2.98, 2.45, and 1.98, respectively. The receiver operating characteristic analysis showed that the area under the curve was 0.75. When we set the cut-off value of the ratio (mediastinal window/lung window) at 0.67, the sensitivity and specificity were 75% and 72%, respectively. CONCLUSIONS Vessel invasion had the greatest impact on recurrence in clinical stage IA non-small cell lung cancer. Our simple computed tomography image analysis showed good predictive performance for vessel invasion.     

Prognostic impact of thrombocytosis in resectable non-small cell lung cancer

Relationship between thrombocytosis and poor prognosis has been reported in lung cancer. However, the majority of previous studies included many advanced stage and small cell lung cancer patients. Few studies focused on resectable non-small cell lung cancer patients. In the present study, therefore, consecutive 240 non-small cell lung cancer patients who received surgical resection were reviewed retrospectively, and investigated the survival impact of preoperative platelet count. In our results, the frequency of preoperative thrombocytosis was only 5.83% (14/240). The 5-year survival of patients with and without thrombocytosis was 28.87% and 63.73%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of thrombocytosis. The present study is the first evaluation of prognostic effect of thrombocytosis in patients with resectable non-small cell lung cancer. Preoperative platelet count was a prognostic factor for resectable non-small cell lung cancer patients.     

Preoperative pulmonary function as a prognostic factor for stage I non-small cell lung carcinoma

BACKGROUND: The aim of this study was to clarify preoperative lung function as a prognostic factor for the long-term survival of, and to discuss the appropriateness of lobectomy for, patients with stage I non-small cell lung carcinoma who have poor preoperative pulmonary function. METHODS: The study group consisted of 402 lobectomized patients with stage I non-small cell lung carcinoma treated by complete resection from 1985 to 1997. Preoperative percent forced vital capacity [(forced vital capacity/predicted forced vital capacity) x 100], FEV(1)% [(forced expiratory volume in 1 second/forced vital capacity) x 100], arterial carbon dioxide tension, and smoking were statistically analyzed as prognostic factors together with other host and tumor biologic factors. RESULTS: Multivariate analysis demonstrated that tumor size (p < 0.0001) was the most significant prognostic factor for survival from primary lung cancer. Age (p < 0.0001), sex (p = 0.0036), and FEV(1)% (p = 0.0046) were found to be independent prognostic factors for survival from death by nonprimary lung cancer-related causes. Smoking was highly correlated with FEV(1)% (correlation coefficient = -0.511; p < 0.0001). The 100 patients with a preoperative FEV(1)% less than 70% included 34 patients with nonprimary lung cancer-related deaths, whereas the 302 patients with an FEV(1)% of 70% or greater included only 23 patients (p < 0.0001). CONCLUSIONS: Along with tumor size, FEV(1)% is the most significant prognostic factor for patients with stage I non-small cell lung carcinoma with regard to survival from death by other causes. Lobectomy may not be preferred as an appropriate surgical modality for patients with stage I non-small cell lung carcinoma with small peripheral nodules who exhibit poor pulmonary function, especially lowered FEV(1)%.     

Prognostic significance of preoperative serum carcinoembryonic antigen level in lung adenocarcinoma but not squamous cell carcinoma.

OBJECTIVES: Clinical significance of measurement of preoperative serum carcinoembryonic antigen (CEA) level in patients with non-small cell lung cancer was investigated. METHODS: Consecutive 271 adenocarcinoma and 112 squamous cell carcinoma patients of non-small cell lung cancer referred to our institute were included in this study. There were 214 men and 169 women, ages ranged from 19 to 90 years, with an average of 64.46 years. Curative resection was performed for 220 adenocarcinoma and 93 squamous cell carcinoma patients. Serum level of CEA was measured before staging or resection of cancer. RESULTS: There is a trend toward a correlation between serum CEA level and stage of the diseases, however, serum CEA level was not always related to tumor node metastasis (TNM) status. In patients with adenocarcinoma, survival rate of patients with an elevated serum CEA level was significantly lower than that with a normal serum CEA level. Multivariate analysis showed that prognostic significance of serum CEA level was TNM staging independent in patients with adenocarcinoma. On the other hand, serum CEA level was not related to patients' survival in patients with squamous cell carcinoma. CONCLUSIONS: Elevated preoperative serum CEA level is a TNM staging independent prognostic factor for patients with adenocarcinoma but not for those with squamous cell carcinoma.     

Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence

The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.     

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.     

Clinical evaluation of VATS lobectomy for lung cancer

Thoracoscopic lobectomy is now recognized as a possible less invasive surgical option for stage I primary non-small cell lung cancer. We have widely used thoracoscopic procedure for surgical diagnosis of lung nodules especially in lung peripheral region as well as resection of primary lung cancer. Results of 47 thoracoscopic lobectomy during last 5 years were compared with 24 standard lobectomy under postero-lateral thoracotomy. There were no significant differences in the duration of surgery, post-operative hospital stay, intraoperative blood loss and post-operative survival. All but three patients who were diagnosed as n 2 disease or tumor with extrapulmonary extension post-operatively are surviving at the time of survey. We conclude that thoracoscopic lobectomy is safe and less invasive procedure compared to standard thoracotomy. We believe it can provide sufficient outcome for stage I non-small cell lung cancer.     

Serum biomarkers facilitate the recognition of early- stage cancer and may guide the selection of surgical candidates: a study of carcinoembryonic antigen and tissue polypeptide antigen in patients with operable non-small cell lung cancer.

OBJECTIVES: Copious literature shows that in lung cancer many serum markers, especially the cytokeratin degradation products, correlate with the extent of disease. In 1995, we suggested the possibility of predicting the resectability of non-small cell lung cancer by measuring the plasma level of the tissue polypeptide antigen, a marker of the cytokeratin family. This study was designed (1) to confirm the earlier data in a new prospective evaluation, (2) to comparatively assess another classic biomarker (ie, the carcinoembryonic antigen), and (3) to incorporate their results into the preoperative evaluation of non-small cell lung cancer. METHODS: We analyzed the database of a single institution over a 5-year period (1994-1998) in a community-based hospital and second referral level institution for a province of 500,000 people. The database included 124 consecutive patients (105 men) with pathologically documented lung cancer (50% with adenocarcinoma) accurately staged, clinically judged operable or potentially operable, and eventually operated on. Anthropometric, clinical, and laboratory data (including the carcinoembryonic antigen and tissue polypeptide antigen serum levels) and the results of a complex staging workup were prospectively recorded. Receiver-operating characteristic curves and diagnostic formulas were used for data analysis. RESULTS: Computed tomography of the thorax, upper part of the abdomen, and brain was the most accurate preoperative method to assess tumor resectability (receiver-operating characteristic area: 0.76, 95% confidence intervals: 0.67-0.86, P =.000; accuracy rate: 77%, confidence intervals: 69%-84%). Tissue polypeptide antigen was also predictive for tumor resectability (receiver-operating characteristic area: 0.62, 95% confidence intervals: 0.51-0.73, P =.035; accuracy rate at a threshold level of 110 U/L: 65%, 95% confidence intervals: 56%-73%). Carcinoembryonic antigen was diagnostic only at the extreme values of its distribution (accuracy rate at a level up to 10 ng/mL: 69%, 95% confidence intervals: 60%-77%). The probability of finding resectable disease at the time of the operation increased from 78% (baseline computed tomography-based probability) to 83% when the concentration of tissue polypeptide antigen was lower than 90 U/L and to 85% when the concentration of carcinoembryonic antigen was below 10 ng/mL. The probability of discovering an advanced disease increased from 68% (baseline computed tomography-based probability) to 89% when tissue polypeptide antigen levels were abnormal and to 100% when carcinoembryonic antigen concentrations were higher than 10 ng/mL. Conversely, the predictability of computed tomography was diminished by contrasting biomarker results, requiring further clinical investigations. CONCLUSIONS: Computed tomography remains the gold standard for the preoperative evaluation of non-small cell lung cancer, although it may significantly underestimate the real tumor extension. The addition of the easy and inexpensive tissue polypeptide antigen test (with or without carcinoembryonic antigen) is capable of correcting this underestimation and helps to decide whether to completely rely on computed tomography or order additional clinical investigations.     

Long-term survival and prognostic factors of five-year survivors with complete resection of non-small cell lung carcinoma

OBJECTIVE: We analyzed the long-term follow-up data on cancer-related death in 5-year survivors of complete resection of their non-small cell lung cancer and examined the prognostic factors having an impact on subsequent survival. METHODS: Of 848 consecutive patients with proven primary non-small cell carcinoma who underwent complete removal of the primary tumor together with hilar and mediastinal lymph nodes, 421 patients (49.6%) survived 5 years or longer after the initial surgical treatment. Of all the data analyzed, only death related to cancer was treated as death. RESULTS: The median follow-up of 5-year survivors was 84 months from the original treatment (range, 60 to 200 months). Their overall survival rate at 10 years was 91.0%. Multivariable Cox analysis demonstrated that although advanced surgical-pathological stage (P =.0001), nodal involvement (P =.0245), male gender (P =.0313), and non-squamous type of the tumor (P =.0034) were significant, independent, unfavorable prognostic determinants in all patients, none of the variables investigated significantly influenced the long-term survival of 5-year survivors. The rate of recurrence beyond 5 years was much lower compared with that within 5 years. In contrast, the rate of occurrence of new malignancies was unchanged throughout the long-term postoperative period. CONCLUSIONS: Among 5-year survivors of complete resection of non-small cell lung cancer, neither stage, nodal status, sex, nor histologic condition further affected subsequent survival, suggesting that the 5-year interval might be sufficient to declare that a patient with lung cancer has been cured.