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J Thorac Cardiovasc Surg 1994;107:1398-1402
© 1994 Mosby, Inc.

GENERAL THORACIC SURGERY

Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lungSignificance of N1 level: lobar or hilar nodes

Fukuoka, Japan

Supported in part by grants-in-aid 62-S-1 and 2-S-1 for Cancer Research from the Ministry of Health and Welfare, Japan.

Received for publication Aug. 24, 1993. Accepted for publication Nov. 12, 1993. Address for reprints: Tokujiro Yano, MD, Department of Chest Surgery, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 815, Japan.

Abstract

The surgical outcome of pathologic N1 disease is controversial. To clarify whether pathologic N1 disease is a uniformly intermediate group or a mixed group of potentially early stage disease and advanced stage disease, we reviewed our previous cases with pathologic N1 disease. We retrospectively investigated 78 patients with pathologic N1 disease who had undergone a complete resection with mediastinal lymph node dissection during the period from April 1972 to December 1990. The cumulative postoperative survival at 5 years was 49.2%. No significant difference in the survival was found according to the following variables: sex, primary site, pathologic T factor, histologic type, type of resection, performance of adjuvant therapy. The lobar lymph nodes (Nos. 12 and 13) were only involved in 30 patients (38.5%), whereas the hilar nodes (Nos. 10 and 11) were involved in 48 patients (61.5%). The survival associated with lobar N1 disease was significantly better than that of hilar N1 disease (64.5% versus 39.7% at 5 years; p = 0.014). In lobar N1 disease, the brain was the most frequent site of distant metastasis, whereas the lungs were the most frequent site in hilar N1 disease. It was suggested that pathologic N1 disease is a mixed group of potentially early stage disease and advanced stage disease with regard to the postoperative prognosis. (J THORAC CARDIOVASC SURG 1994;107: 1398-1402)

The existence of regional lymph node metastasis is the most important prognostic factor for resectable lung cancer. Pathologic N2 (pN2) disease involving the mediastinal lymph nodes is at the advanced stage, and the surgical outcome is poor with a 5-year survival of 19% to 29%. ^1-5 On the other hand, pN0 disease with either a pT1 or pT2 primary tumor (pathologic stage I) is presumed to indicate early disease with a 5-year survival of 60% to 70% after resection. ^6-8 Pathologic N1 disease is an intermediate group in the disease progression between pN0 disease and pN2 disease. However, the surgical outcome of pN1 disease is controversial. In the present study, we reviewed our previous cases with pN1 disease and assessed whether pN1 disease is a uniformly intermediate group or a mixed group of potentially early stage disease and advanced stage disease.

PATIENTS AND METHODS

We reviewed the hospital charts of 549 patients with non-small-cell carcinoma of the lung, which had been completely resected at the National Kyushu Cancer Center during the period from April 1972 to December 1990. Complete resections consisted of either a lobectomy or pneumonectomy together with a total dissection of the regional lymph nodes (ipsilateral hilar and mediastinal system). In all cases, the resection margin was microscopically proved to be negative for tumor cells. The staging of all patient conditions is reported according to the new International Staging System for Lung Cancer. ⁹

Of those 549 patients, 81 had pN1 disease (384 pN0 disease, 84 pN2 disease). Excluding three patients who died within 30 postoperative days as a result of operation-related causes (3.7% of mortality rate), we selected 78 patients with pN1 disease in this retrospective study. The characteristics of those patients are listed in Table I. They consisted of 58 men and 20 women with a mean age of 60.3 years. Forty-one primary tumors were located in the right lung, and 37 were in the left lung. Nineteen pT1 primary tumors, 56 pT2 tumors, and 3 pT3 tumors were found. The tumors were histologically classified as squamous cell carcinoma in 41 cases, adenocarcinoma in 32, large-cell carcinoma in three, and adenosquamous cell carcinoma in two. As for the type of resection, a lobectomy was performed in 46 patients, a bilobectomy in seven, and a pneumonectomy in 25. Postoperatively, adjuvant chemotherapy was performed in 42 patients, whereas radiation treatment was done in only 11 patients. Forty-six consecutive patients, who underwent operations after January 1983, entered randomized studies of postoperative adjuvant chemotherapy with cisplatin-based regimens (chemotherapy versus no treatment).

The Beccel Mark-II statistical package program (version 4.0, Beccal, Inc., Tokyo, Japan) was used in all statistical analyses. Survival after operation was estimated by the method of Kaplan and Meier. ¹⁰ The influence of variables on survival wasanalyzed by means of the log-rank test. ¹¹ The Cox proportional hazards model technique was used to identify which factors had a jointly significant influence on survival. ¹² Allreported p values were two-sided.

RESULTS

For all 78 patients with pN1 disease, the cumulative postoperative survival at 5 years was 49.2% (Fig. 1). The association of various prognostic factors to postoperative survival (i.e., sex, primary site, pT factor, histologic type, type of resection, adjuvant chemotherapy, and adjuvant radiotherapy) were all examined by a univariate analysis. As summarized in Table II, no significant differences in the survival were found according to those variables.

View larger version (9K): [in this window] [in a new window]   Fig. 1. Survival curve after resection for patients with N1 non-small-cell lung cancer. Bars denote standard errors.

View larger version (13K): [in this window] [in a new window]   Fig. 2. Survival curves after resection for patients with N1 disease according to the level of involved N1 nodes. Lobar node metastasis versus hilar node metastasis; p = 0.014.

The surgical outcome of pN1 non-small-cell carcinoma is controversial, as is the efficacy of adjuvant therapy with chemotherapy, radiotherapy, or both. ^13-16 The outcome often depends on the radicality of mediastinal lymph node dissection. Radical mediastinal lymphadenectomy is necessary for the pathologic determination of nodal status. Some N2 diseases might be underestimated to be N1 disease if the mediastinal lymph nodes were not systematically dissected. In the series that included the performance of radical mediastinal lymphadenectomy, the 5-year survival of pN1 disease ranged from 40% to 49%. ^16-18 Similarly, it was 49.2% in our series. Those results are still better than in cases where a radical lymphadenectomy was not performed. Therefore, more than a 40% 5-year survival is essential when we assess the prognostic factors and the efficacy of adjuvant therapy in pN1 disease.

In the present study, histologic types, pT factors, types of pulmonary resection, and the use of adjuvant therapy were found to have no effect on the postoperative survival with pN1 disease. Our results are compatible with previous studies, ^16,18 except forthe pT factors in the study of Naruke and associates, ¹⁷ in which they reported a better survival associated with T1 tumors than that with T2 or T3 tumors. As for the N1 status, Martini and associates ¹⁶ proposed the number of involved N1 nodes to be a significant prognostic factor. On the other hand, Naruke and associates ¹⁷ claimed better survival with intrapulmonary or peribronchial lymph node metastases. In fact, it is often difficult to define the number of metastatic nodes because several metastatic nodes are easily conglomerated and hardly divided. N1 disease with only intrapulmonary node metastases is too small an entity to classify N1 disease regarding prognosis. Therefore, we analyzed postoperative survival by classifying pN1 disease into lobar and hilar N1 diseases. We observed a significant difference in prognosis between lobar and hilar N1 diseases by both univariate and multivariate analyses. The postoperative survival with lobar N1 disease with 65% at 5 years was better than that of hilar N1 disease and was comparable with the survival with pN0 disease. The pattern of postoperative recurrence (local or distant) in lobar N1 disease was similar to that in hilar N1 disease. However, a difference was found in the first site of distant metastasis. From an anatomic perspective, it is thought that the lungs are not likely to be the first site of hematogenous metastasis in pN0 disease. On the other hand, pN2 disease has a prevalence of pulmonary metastases because of the presence of a direct flow into the superior vena cava from the N2 nodes (Yano et al.: In preparation). In the pattern of distant metastasis, hilar N1 disease seems to be similar to N2 disease, whereas lobar N1 disease seems to be similar to N0 disease.

In conclusion, we suggested that pN1 disease is not a uniformly intermediate group but a mixed group of both potentially early stage disease and potentially advanced stage disease with regard to prognosis.

Acknowledgments

We thank Dr. B. T. Quinn, Kyushu University, for his critical review and Yumiko Oshima and Yuko Ishibashi for their expert help in the preparation of this manuscript.

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yukito Ichinose Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yano, T. Articles by Ichinose, Y. Search for Related Content PubMed PubMed Citation Articles by Yano, T. Articles by Ichinose, Y.