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Ann Thorac Surg 1996;62:1016-1020
© 1996 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Results of Resection of T3 Non–Small Cell Lung Cancer Invading the Mediastinum or Main Bronchus

Departments of Pulmonology, Thoracic Surgery, and Pathology, Sint Antonius Hospital, Nieuwegein, the Netherlands

Accepted for publication May 4, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background. T3 tumors can be divided into several subgroups. Surgical treatment of T3 tumors with chest wall invasion results in good survival. This study shows the results of resection of T3 non–small cell tumors located in the main bronchus or with invasion of mediastinal structures.

Methods. From 1977 through 1993, 108 patients underwent resection for primary non–small cell carcinomas located in the main bronchus or with invasion of mediastinal structures. A complete resection was performed in 70 patients (64.8%). Actuarial survival time was estimated and risk factors for late death were identified.

Results. Overall hospital mortality was 8.3%. All deaths followed pneumonectomy. Mean 5-year survival was 29% for all hospital survivors, 35% for patients with complete resection, and 18% for patients with incomplete resection (p = 0.03). In patients with complete resection, mean 5-year survival was 45% for N0 patients and 37% for N1 patients. There were no 5-year survivors in the group of N2 patients. The mean 5-year survival was greater (but not statistically significantly greater) in patients with tumors located in the main bronchus (40%) than in patients with tumors with invasion of mediastinal structures (25%) (p > 0.05). Histology, tumor spill, age, sex, and type of operative procedure were not significant prognostic factors.

Conclusions. Patients with tumors located in the main bronchus have a better survival than patients with invasion of the mediastinal structures. Pneumonectomy increases hospital mortality. Incompleteness of resection and mediastinal lymph node involvement influence survival significantly.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
See also page 1020.

Pulmonary resection is the treatment of choice for non–small cell bronchogenic carcinoma if there are no distant metastases. Resectability is closely related to the stage of the disease [1]. Whereas stage I and stage II tumors are considered to be resectable [2], the role of resection for stage III tumors remains controversial.

Stage III tumors can be divided into stage IIIa and stage IIIb tumors. Stage IIIa tumors include tumors with limited extrapulmonary extension of the primary tumor, like invasion of the superior sulcus, chest wall, mediastinal structures, pericardium, or diaphragm, or tumors with endobronchial proximity to the main carina. According to the TNM classification, these tumors are staged as T3 [3].

Resection shows good survival results in bronchogenic carcinoma involving the chest wall [4, 5]. Our previous study [6] was in agreement with these findings.

The present report concerns 108 patients who underwent resection because of T3 tumors with invasion of the mediastinal structures, pericardium or with localization in the main bronchus. It is a retrospective study to analyze survival characteristics.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
From 1977 to 1993, 2,009 patients with bronchogenic carcinoma had a resection at our hospital. Of this group, 108 patients (5.4%) underwent operation for T3 non–small cell bronchogenic carcinoma with invasion of the mediastinal structures or pericardium, or localization in the main bronchus at pathologic examination. Patients with distant metastases, synchronous tumors, and recurrences were excluded. Resection was considered as complete when (1) the surgeon was morally certain that all known disease was removed, (2) resection margins were free at pathologic examination, and (3) the highest mediastinal lymph node was negative by microscopy. Peroperative tumor spill was scored separately.

Ages ranged from 31 to 82 years with a mean of 60 years. One hundred three patients were male and 5 were female. Ninety-eight patients (91%) were smokers.

The most common complaints were cough (75%), dyspnea (47.2%), hemoptysis (39.8%), weight loss (27.8%), thoracic pain (25%), and hoarseness (12%). Sixteen patients (14.8%) presented without symptoms. A preoperative diagnosis was obtained in 105 patients (97.2%). Bronchoscopy was diagnostic in 99 patients, and percutaneous needle aspiration biopsy of the lung and sputum cytology were diagnostic in 3 patients each.

Fifty-seven tumors were located on the right side and 51 tumors on the left side. Cervical mediastinoscopy was negative in 98 patients (90.7%) and positive in 5 (4.6%). The latter group was operated on because they only had a positive lymph node at the ipsilateral tracheobronchial angle (n = 3) or because they were relatively young (51 and 56 years) (n = 2). The type of resection and tumor localization are shown in Table 1. A complete resection was achieved in 70 patients (64.8%), 46 patients with localization in the main bronchus, 21 patients with involvement of the mediastinal structures, and 3 patients with localization in the main bronchus and invasion of the mediastinal pleura. Resections were incomplete due to positive resection margins (87%) and positive lymph nodes (13%). A combined heart-lung operation was performed in 2 patients: 1 patient had a pneumonectomy and a coronary artery revascularization and 1 patient had a pneumonectomy and an aortic valve replacement. Four patients had a pneumonectomy and a tracheobronchial reconstruction because of positive resection margins. Peroperative tumor spill occurred in 5 patients (4.6%). The histologic diagnosis was squamous cell carcinoma in 90 patients (83.3%), adenosquamous cell carcinoma in 8 patients (7.4%), adenocarcinoma in 5 patients (4.6%), and large cell carcinoma in 5 patients (4.6%).

Follow-up was complete as of January 1995. Follow-up data were obtained from hospital files and from questionnaires to referring pulmonary physicians and general practitioners. Follow-up about local recurrence or distant metastases was achieved in 95.4% of the patients.

Survival was estimated from the date of operation, using the Kaplan-Meier survival analysis method [7]. Hospital deaths were excluded. Survival comparisons were analyzed by the log rank test [8]. The difference was considered statistically significant when the p value was less than 0.05. Incremental risk factors affecting survival were evaluated using Cox's proportional hazards model [9].

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Hospital mortality was 8.3% (pneumonectomy, 10.1% [9/89]; lobectomy, 0% [0/19]). Regarding the localization of the tumor, hospital mortality was 8.8% (6/68) for tumors localized in the main bronchus, 3% (1/33) for tumors with involvement of mediastinal structures, and 28.6% (2/7) for tumors with involvement of the main bronchus and mediastinal structures. Six deaths were due to bronchopleural fistula in the postoperative period, one to sepsis, one to cardiac arrest, and one to adult respiratory distress syndrome.

Of 6 patients with bronchopleural fistula, 5 had a tumor located on the right side and 1 on the left side. In all patients the bronchial stump had been covered with surrounding tissue. The operation was incomplete because of massive residual carcinomatous tissue at the bronchial stump in 1 patient. This was the only patient who had received preoperative radiotherapy in whom a bronchopleural fistula developed. In another patient with a bronchopleural fistula the operation was incomplete because of positive mediastinal lymph nodes. In 4 patients sutures of 3-0 Vicryl (Ethicon, Somerville, NJ) were used to close the main bronchus. A stapler was used in the remaining 2. For patients 60 years of age or younger, hospital mortality was 7.0% (4/57), compared with 9.8% (5/51) for those older than 60 years.

Estimated mean 5-year survival was 27% for all patients (n = 108) and 29% for hospital survivors (n = 99).

Complete resection was performed in 64 hospital survivors (64.6%) with a mean 5-year survival of 35%. The remaining 35 hospital survivors underwent an incomplete resection with a mean 5-year survival of 18% (p = 0.03) (Fig 1). Because of this significant difference in survival between patients with complete and incomplete resection, only the results of hospital survivors with complete resection were studied for the analysis of other prognostic factors.

View larger version (17K): [in this window] [in a new window]   Fig 1. . Estimated mean 5-year survival in patients with complete resection (solid line) and incomplete resection (dashed line).

View larger version (19K): [in this window] [in a new window]   Fig 2. . Estimated mean 5-year survival after complete resection with lymph node involvement (N1 [dashed line], N2 [dotted line]) and without lymph node involvement (N0 [solid line]).

Patients with squamous cell carcinoma had a better mean 5-year survival than patients with adenocarcinoma, adenosquamous cell carcinoma, or large cell carcinoma, but the difference was not statistically significant (37% and 22%, respectively; p = 0.31).

In the group of patients with complete resection, postoperative radiotherapy did not improve survival. On the contrary, mean 5-year survival of patients who received radiotherapy was 17%, whereas patients who were not irradiated had a mean 5-year survival of 39% (p = 0.01).

Patients younger than 60 years had a better survival than older patients (38% and 31%, respectively). This difference was not significant, but when a new classification into patients younger than 70 years and older was made, the difference was of borderline significance (p = 0.05). Sex, tumor spill, and type of operative procedure did not influence survival significantly.

According to the multivariate analysis regarding age, sex, pTNM classification, histology, localization, and tumor spill, only mediastinal lymph node involvement was a significant prognostic factor (Table 4).

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Surgical treatment of non–small cell bronchogenic carcinoma is closely related to the stage of the disease [1]. Some selected T3 tumors are potentially resectable. Patients with bronchogenic carcinoma involving the thoracic wall have good survival rate when a complete resection is performed and there are no mediastinal metastases [4, 5]. Similar results have been published about tumors located in the main bronchus [10–14]. Although some studies about tumors invading the mediastinum have been published [15–18], the role of resection for carcinomas invading the mediastinal structures remains unclear.

The present study was undertaken to analyze survival characteristics of patients with T3 tumors in the main bronchus or with invasion of mediastinal structures. Comparison with other reports is sometimes difficult due to differences in patient selection, tumor invasion, operative procedure, and statistical analysis.

Hospital mortality was 8.3%. It was closely related to type of operation: pneumonectomy had a higher hospital mortality (10.1%) than lobectomy (0%). This concurs with the results of others [11, 12]. Although hospital mortality is high, mean 5-year survival of complete resection by pneumonectomy is still 37%.

Mortality was particular high in patients with a tumor with carinal proximity (8.8%) in contrast to patients with a tumor invading mediastinal structures (3%). Our findings agree with the results published, where hospital mortality for tumors with carinal proximity varies between 6% and 11% [10–12], whereas tumors invading mediastinal structures have a hospital mortality of 3% to 6% [16, 18], although it must be noticed that this study included more pneumonectomies in the group of patients with a tumor in the main bronchus.

An important source of postoperative problems was a bronchopleural fistula, which developed in 7 patients. Six of them died in the postoperative period. In the literature the prevalence of bronchopleural fistula ranged from 2% to 10% [19]. Operative mode (pneumonectomy with bronchoplasty), residual carcinomatous tissue at the stump, preoperative radiotherapy, and diabetes mellitus are significant risk factors [19]. In this study, all patients with bronchopleural fistula had pneumonectomy and a tumor located in the main bronchus. This stresses the importance of surgical technique in this type of tumor. Only 1 patient was irradiated preoperatively and had positive resection margins at the bronchus stump. Although age is often correlated with operative mortality, no significant correlation was found in this study.

The estimated mean 5-year survival for 99 hospital survivors was 29%. This is similar to the results of others [12, 13, 18]. In patients with complete resection the mean 5-year survival was 35%, whereas patients with an incomplete resection had a mean 5-year survival of 18%.

Regarding the localization of the tumor, patients with bronchogenic carcinoma located in the main bronchus had a better mean 5-year survival (40%) than patients with a tumor invading mediastinal structures (25%), although the difference was not statistically significant. This was also described by Nakahashi and associates [15], who found a 4-year survival of patients with invasion of the main bronchus of 80%, demonstrating that this subcategory of T3 tumors had a favorable prognosis.

Based on the promising results of chemotherapy in patients with N2 tumors, the use of induction chemotherapy or chemoradiotherapy before resection becomes relevant in bronchogenic carcinoma involving mediastinal structures to improve completeness of resection and survival.

Like other reports [15, 16, 20], mediastinal lymph node involvement had a poor prognosis. In this study, no patient with mediastinal lymph node involvement survived more than 5 years.

Histologic analysis showed no statistically significant difference in mean 5-year survival between patients with squamous cell carcinoma and adenocarcinoma, adenosquamous cell, or large cell carcinoma, although the first patient group had a better mean 5-year survival (37% versus 22%). This is also described by others [17, 20], although Martini and associates [18] found a better survival for patients with adenocarcinoma.

Patients with complete resection who received postoperative radiotherapy had a worse survival than patients who were not irradiated (17% versus 39%). A possible reason for this difference is the fact that 50% (6/12) of patients with complete resection who received radiotherapy had N2 disease, which is associated with a poor prognosis.

Comparing the results of this study with the results of complete resection of other T3 bronchogenic carcinoma involving the chest wall [6], patients with a tumor located in the main bronchus had the best prognosis, but the difference was not statistically significant (mean 5-year survival was 40% and 25%, respectively).

In conclusion, complete resection in patients with invasion of mediastinal structures shows moderately good results, whereas patients with involvement of the main bronchus have a superior survival rate. Mediastinal lymph node involvement worsens the prognosis significantly.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
We thank Mrs Joke van der Sluis for her secretarial support. This study was supported by a grant from the Mr Willem Bakhuys Roozeboom Foundation.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr van den Bosch, Department of Pulmonology, Sint Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein, the Netherlands.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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