Eur J Cardiothorac Surg 1998;14:152-155
© 1998 Elsevier Science NL
Long-term survivors with pN2 non-small cell lung cancer after a complete resection with a systematic mediastinal node dissection
Tokujiro Yano1,*,
Yasuro Fukuyama,
Hideki Yokoyama,
Shinji Kuninaka,
Yasuhiro Terazaki,
Tadashi Uehara,
Hiroshi Asoh,
Yukito Ichinose
Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka, Japan
Received 18 November 1997;
received in revised form 16 March 1998;
accepted 12 May 1998.
* Corresponding author. Department of Chest Surgery, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 811–1395, Japan. Tel.: +81 92 541 3231; fax: +81 92 551 4585.
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Abstract
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Objective: A substantial number of surgical patients with pN2 disease have survived longer than 5 years without any evidence of recurrence, although the surgical indications for those patients remain controversial. The present study was performed in order to clarify the clinical characteristics of the long-term survivors with pN2 disease. Methods: We retrospectively reviewed the cases of 111 patients with pN2 disease who had undergone a complete resection with a systematic mediastinal lymph node dissection from 1974 through 1991. Results: Of the 111 patients with pN2 disease, 20 survived longer than 5 years after a surgical resection. When both the pre- and post-operative conditions were compared between the long-term survivors and the others, the long-term survivors were characterized by significantly higher proportions of cN0 disease (P=0.031), pT1 disease (P=0.004), skip metastasis without hilar node metastasis (P=0.028), and metastasis of a single mediastinal station (0.044). Of those characteristics, only the likelihood of having cN0 disease could be pre-operatively determined. The survival rate of such a population with cN0-pN2 disease was 34.5% at 5 years and 29.6% at 10 years after a complete resection, respectively. Conclusions: Pathologic N2 patients with some favorable prognostic factors can survive long-term after a complete resection combined with a systematic mediastinal lymph node dissection. At present, due to the lack of any effective adjuvant therapy, a systematic mediastinal node dissection should be routinely performed even in patients with cNO disease.
Key Words: Non-small cell lung cancer • pN2-disease • Long-term survivors • Systematic mediastinal node dissection • cNO-pN2 disease
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Introduction
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The surgical results of pN2 non-small cell lung carcinoma remain poor regardless of whether, or not, a complete resection with systematic hilar mediastinal lymph node dissection is performed. In order to improve the surgical results various post-operative adjuvant therapies, including radiotherapy and chemotherapy, have been performed, but with little success
[1]
[2]
[3]
[4].
However, several favorable factors for the postoperative survival of pN2 disease have been reported
[5]
[6]
[7]
[8]
[9]
[10]. A substantial number of surgical patients with pN2 disease have survived longer than 5 years without any evidence of recurrence. Therefore, it is important to clarify the clinical characteristics of the long-term survivors with pN2 disease in order to better select the patients who should undergo a systematic mediastinal node dissection with a potentially curative intent.
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2. Patients and methods
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We retrospectively reviewed the cases of 114 patients with pN2 non-small cell lung cancer, who had undergone a complete resection with systematic mediastinal lymph node dissection at the National Kyushu Cancer Center during the period between 1974 and 1991. Of those, three patients who died within 30 days after surgery due to operation-related diseases were excluded from the present study. All other 111 patients were followed for longer than 5 years. A mediastinoscopic examination was not performed as part of the pre-operative staging, even in patients with cN2 disease, since resectable diseases are all subject to a thoracotomy at our institute. A pre-operative evaluation of the mediastinal nodal status varied as follows. Before 1980 (20 patients), the mediastinal nodal status was based primarily on both the roentgenographic and bronchoscopic findings of the trachea, the carina and the main bronchus. Since 1980 (91 patients), lymphadenopathy was routinely investigated by CT scanning. During the period between 1980 and 1983 (23 patients), mediastinal lymph nodes measuring 1.0 cm or greater in the short axis were defined as positive. Since 1984 (68 patients), we have classified a CT scan as being positive for pN2 disease when the product of the long axis (cm) x short axis (cm) was either 1.5 cm or greater in a single node or 1.0 cm or greater in more than one node.
Complete resections consisted of either a lobectomy or a pneumonectomy together with the regional lymph node dissection. Regardless of the pre-operative evaluation of nodal status, a systematic mediastinal lymph node dissection was routinely performed according to the lymph node map proposed by the Japan Lung Cancer Society
[11]. On the right side, the mediastinal pleura was longitudinally opened along the trachea and esophagus. All accessible nodes in the superior mediastinum (no. 1 superior mediastinal, no. 2 paratracheal, no. 3 pretracheal, no. 4 tracheobronchial nodes) and the inferior one (no. 7 subcarinal, no. 8 paraesophageal, no. 9 pulmonary ligament), were dissected out with the surrounding fat tissue. On the left side, the mediastinal pleura was opened both above and beneath the aortic arch, and all accessible nodes (no. 2, 3, 4, 5 subaortic, no. 6 paraaortic, no. 7, 8, 9) were dissected as far as possible, although there were anatomical limitations (aortic arch) regarding the access to the superior mediastinum. The post-operative stage of the disease was based on a histologic examination of the resected specimen and the lymph nodes.
Post-operatively, adjuvant chemotherapy with cisplatin-based regimens was perfomed in 63 patients, whereas radiation treatment was done in 51 patients either with (27 patients), or without (24 patients), chemotherapy. The allocation of patients to those adjuvent therapies varied mainly according to the era, independent of individual histological type, T factor or N2 status of patients.
The survival data from the date of surgical resection were analyzed using the Kaplan–Meier actuarial method, while the patient counts were analysed by the 
2 and Fisher exact tests.
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Results
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Fig. 1
shows the overall survival after a complete resection for pN2 non-small cell lung cancer. The 1 year, 3 year, 5 year and 10 year survival rates were 71%, 33%, 18%, and 15%, respectively. Therefore, it was reasonable to assume that long-term survivors could be defined as the patients who survived longer than 5 years after surgery.
Table 1 shows the pre-operative conditions of 20 long-term survivors in comparison with the 91 patients who died within 5 years after surgery. The pre-operative characteristics were comparable in the two groups except for the clinical N status. A significantly higher proportion of cN0 disease was observed in the long-term survivors than in the others (P=0.031).
Regarding post-operative conditions (Table 2), the long-term survivors were characterized by significantly higher proportions of pT1 disease (P=0.004), skip metastasis without hilar node metastasis (P=0.028) and metastasis of a single mediastinal station (P=0.044) in comparison to the non-long-term survivors.
Based on the above analysis, the only identifiable pre-operative characteristic of the long-term survivors was a likelihood of having cN0 disease. However, the definition of cN0 disease has historically varied according to the era. Since 1984, the diagnosis of clinical N factor with CT has been routinely based on the criteria stated in 'Section 2'. From 1984 to 1993, 40 (14.3%) of 284 consequent patients with cN0 disease were post-operatively diagnosed to have pN2 disease. An overall survival curve of those 40 patients with cN0-pN2 disease is shown in
Fig. 2
. The 5 years survival rate was 34.5%, and thereafter the curve reached a plateau of about 30%.
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Fig. 2. Survival curve of patients with cN0-pN2 disease. From 1984 through 1993, the diagnosis of clinical N factor with CT has been routinely based on the same criteria as described in the 'Patients and methods' section. Forty of 284 consequent patients with cN0 disease were postoperatively diagnosed to have pN2 disease.
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Discussion
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The prognostic factors of resected pN2-disease have already been studied by other authors on the basis of the actuarial survival analysis. However, such studies often suffered from an insufficient follow-up duration with an unreliable tail of the survival curve. Thus, such findings might not accurately reflect the profile of potentially curative pN2 disease. In the present study, we first demonstrated the clinical profiles of long-term survivors with pN2 disease who did survive longer than 5 yr after a complete resection with systematic mediastinal lymph node dissection. They were characterized by the likelihood of having cN0 disease, pT1 disease, skip metastasis or single station metastasis. Similar studies on long-term survivors with pN2 disease were presented by 11 domestic institutes at the 14th annual meeting for the Japanese Association for Chest Surgery in May 1997 (Kanazawa, Japan)
[12]. As summarized in Table 3, all institutes pointed out at least one of the above-mentioned characteristics for long-term survivors.
All of those characteristics of the long-term survivors seem to demonstrate less potential for tumor proliferation. Having pT1 disease and cN0 disease (an absence of significantly swelling nodes) might thus indicate that the tumors cannot aggressively grow in either the primary site or in the metastatic lymph nodes, respectively. Furthermore, skip metastasis or single station metastasis might also indicate that the tumor cells are also not able to prevalently reside and grow in the lymph nodes although they do have a potential to migrate to the regional lymph nodes.
A likelihood of having cN0 disease was thus found to be the only pre-operative characteristic of long-term survivors with pN2 disease. The criteria for abnormal mediastinal nodes (cN2) on CT scans vary among the institutes. However, the difference in the criteria of cN2 disease does not seem to cause any great difference in the diagnosis of pN2 disease
[13]
[14] since the evaluation of nodal status with a CT scan is primarily based on the size of the lymph nodes. Nevertheless, `cN0' on a CT scan only indicates the absence of significantly swollen nodes. Like our patients in the present study, the patients with cN0-pN2 disease were reported to survive significantly longer than those with cN1- or cN2-pN2 disease
[6]
[7]. The 5-year survival rate of those patients was about 30%. As a result, curative pN2 disease by surgery tends to be present in cN0 disease. Both theoretically and practically, a mediastinoscopical examination cannot rule out pN2 disease although it can identify pN2 disease. Therefore, mediastinal node sampling with a mediastinoscopy or even under a thoracotomy might lead to an incomplete resection in potentially curative cN0-pN2 diseaes. To obtain long-term survivors with pN2 disease, there is presently no way other than the routine performance of a systematic mediastinal lymph node dissection even when patients have cN0 disease.
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Acknowledgments
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We thank Dr. B.T. Quinn, Kyushu University, for his critical review and Yumiko Oshima for her expert help in the preparation of this manuscript.
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Footnotes
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1 Present address: Department of Surgery II, Kyushu University, Fukuoka Japan. 
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Abstract
Introduction
