Lymph Node MetastasG Tsuguo Naruke, M.D., Tomoyuki Goya, M.D., Ryosuke Tsuchiya, M.D., and Keiichi Suemasu, M.D.

Transcription

1 ORIGINAL ARTICLES The Importance of Surgery to Non-Small Cell Carcinoma of Lung with Mediastinal Lymph Node MetastasG Tsuguo Naruke, M.D., Tomoyuki Goya, M.D., Ryosuke Tsuchiya, M.D., and Keiichi Suemasu, M.D. ABSTRACT In the past 25 years, 1,654 patients with nonsmall cell cancer underwent resection at National Cancer Center Hospital, Tokyo. A comparative study has been made of 5-year survival of patients who had pulmonary resection with and without mediastinal lymph node dissection. There were 426 patients (25.8% of the total) with N2 MO disease. Of these, 345 underwent pulmonary resection with mediastinal lymph node dissection. The 5-year survival in this group was 15.9% (T1 N2 MO, 30.0%; T2 N2 MO, 14.5%; and T3 N2 MO, 12.9%). In the remaining 81 patients, who did not have mediastinal lymph node dissection, 5-year survival was 6.7%. Of the 426 patients with N2 MO disease, 242 were select patients who underwent a curative operation with an overall 5-year survival of 19.2%. Sixty-six of them had squamous cell carcinoma and a 5-year survival of 30.8%; 153 had adenocarcinoma and a survival of 16.0%; 14 had large cell carcinoma and a survival of 12.8%; and 9 had adenosquamous cell carcinoma, and none survived 5 years. To improve the end results, it is important to perform as many curative operations with mediastinal lymph node dissection as possible. Histological cell type and tumor status must be taken into consideration. There is no controversy over the fact that early detection of lung cancer and early determination of the need for operation in as early a stage as possible are necessary for improvement in the end results of treatment. However, because the prognosis for patients with lung cancer and metastasis to mediastinal lymph nodes has been very poor after operation, the need for operation in these patients is controversial. To date, there have been few reports on the surgical treatment of patients with lung cancer with metastasis to mediastinal lymph nodes. However, despite studies [l-41 published in the 1960s and 1970s that claimed operations should not be performed in such patients because of the extremely poor prognosis, the number of studies that report operations on such patients has been increasing (Table 1) [ From the National Cancer Center Hospital, Tokyo, Japan. Accepted for publication May 11, Address reprint requests to Dr. Naruke, Department of Surgety, National Cancer Center Hospital, No. 1-1, 5-chome, Tsukiji, Chuo-ku, Tokyo 104, Japan. For the past 25 years at the National Cancer Center Hospital in Tokyo, the standard, in general, has been to combine resection of lung cancer with dissection of mediastinal lymph nodes. This long experience gave us the opportunity to review the importance of dissection of mediastinal lymph nodes in the surgical treatment of lung cancer. In this report, we compare the survival of patients with and without dissection of metastases to mediastinal lymph nodes. Material and Methods From May, 1962, to December, 1986,3,937 patients with lung cancer were treated at the National Cancer Center Hospital, Tokyo. Based on the 1978 staging system of the Union Internationale Contre le Cancer (UICC), 6 patients were in Stage 0; 798 were in Stage I; 180 were in Stage 11; 1,424 were in Stage 111; 1,529 were in Stage IV. Thoracotomy was performed in 1,950 patients; 1,832 underwent resection and 118, exploratory thoracotomy. The rate of resectability among the patients having thoracotomy was 93.9%. A total of 1,654 patients were analyzed. Excluded were 54 patients with small cell carcinoma, 44 with multiple primaries, 29 with unclassified disease, 45 with low-grade malignancies, and 6 with sarcoma. Of the 1,654 patients, 1,265 were men and 389 were women. They ranged in age from 27 to 87 years. Five patients were in their 20s; 39, in their 30s; 175, in their 40s; 448, in their 50s; 661, in their 60s; 303, in their 70s; and 23, in their 80s. As a rule, staging was determined according to the TNh4 postsurgical-histopathological classification of the UICC. Of the 1,654 patients, 1,389 had mediastinal lymph node dissection and 265 did not. For 83 of the 265 patients, a pathological examination was performed using samples of mediastinal lymph node. For the remaining 182 patients, the decision was based on surgical staging from the findings at thoracotomy. Postoperative death within 30 days was included in the survival study. There were 31 such deaths in the dissection group; 8 patients were in Stage I, 2 in Stage 11, 16 in Stage 111, and 5 in Stage IV. In the group who did not have dissection, there were 13 deaths; 6 in Stage 111 and 7 in Stage IV. Mediastinal lymph node dissection was not done in 265 patients for various reasons. Of the 41 patients in Stage I, 24 were in a poor condition generally, 15 were thought to have no lymph node metastasis by the findings at thoracotomy; 1 had had preoperative irradiation and was eliminated for technical reasons, and 1 was 603 Ann Thorac Surg 46: , Dec Copyright by The Society of Thoracic Surgeons

2 604 The Annals of Thoracic Surgery Vol46 No 6 December 1988 Table 1. Summary of Reports on Resected N2 Lung Cancer Reference Naruke et a1 (National Cancer Center Hospital, Japan) [5] Smith (Walsgrave Hospital, UK) [61 Rubinstein et a1 (Chaim Sheba Medical Center, Israel) [7] Kirschner (Mount Sinai Medical Center, NY, USA) [8] Kirsh and Sloan (University Hospital, MI, USA) [9] Pearson et a1 (Toronto General Hospital, Ont, Canada) [lo] Martini et a1 (Memorial Sloan- Kettering Cancer Center, NY, USA) [ll] Hitomi and Taki (Chest Disease Research Institute, Kyoto UNversity, Japan) [12] Suemasu et a1 (collected cases, Japan) ~ 3 1 Nishiyama et a1 (20 collected institutes, Japan) 1141 Year Period of No. of Resections Patients Diagnosis of N2 ~ Thoracotomy Thoracotomy 29 Thoracotomy Mediastinoscopy 18 Thoracotomy Mediastinoscopy (+ ) 9 18 Mediastinoscopy (-) Thoracotomy Thoracotomy 29 Mediastinoscopy andor thoracotomy Thoracotomy 24 Thoracotomy Squamous 5-Year Cell SuMval Carcinoma (%) (%) misjudged as having an advanced stage of disease. Of the 3 patients in Stage II, 2 were thought to have no metastasis and 1 was in poor health. Of the 116 patients with Stage 111 disease, 100 had advanced disease, 7 were thought to have no metastasis, 4 had preoperative irradiation, and 5 were in poor condition. Of the 105 patients in Stage N, all had advanced disease. Descriptions of lymph node metastasis were made in conformity with the criteria [5] proposed by the Committee on Description for Operation [15]. 1. The superior mediastinal lymph nodes correspond to the upper one-third of that part of the trachea within the thorax. These include the nodes located around the trachea, the site of which is defined by the horizontal line at the top of the upper rim of the subclavian artery and the horizontal line at the center point of the trachea where the upper rim of the brachiocephalic vein ascends to the left, crossing in front of the trachea. 2. The paratracheal lymph nodes correspond to the space between numbers 1 and 4, and exist on the lateral side of the trachea. Number 4 is classified into pretracheal(3), retrotracheal(3p), and anterior mediastinal (3a). The posterior portion of the trachea is called retrotracheal or 3p, and the anterior portion of the brachiocephalic vein and the superior vena cava is called anterior mediastinal or 3a. 4. The tracheobronchial lymph nodes are located on or very close to the obtuse angle between the trachea and main bronchi. The nodes on the right side are in the obtuse angle level with and inside the azygos vein. The nodes on the left are on the median side of the subaortic lymph nodes. 5. The subaortic lymph nodes are the lymph nodes at the ligamentum arteriosum. 6. The paraaortic lymph nodes are the lymph nodes in the outer walls of the ascending aorta and aortic arch and anterior to the vagus nerve. 7. The subcarinal lymph nodes are the lymph nodes at the point where the trachea divides into the main bronchi. 8. The paraesophageal lymph nodes are the lymph nodes under the level of the subcarina of the trachea and adjacent to the esophagus. 9. The pulmonary ligament lymph nodes are the lymph nodes inside the ligament. The lymph nodes in the posterior wall and lower part of the inferior pulmonary vein are also included. Numbers 1 to 9 represent mediastinal lymph nodes. Numbers 10 through 12 include the Mar lymph nodes,

3 605 Naruke et al: Non-Small Cell Carcinoma of the Lung with Metastasis Table 2. Comparison of 5-Year Survival between Patients with and without Dissection of Mediastinal Lymph Nodes With Dissection 5-Year Survival Without Dissection No. of % % Total Surviving Stage Patients No. surviving No. surviving (%) 1 617" II III IV Total 1,654 1, This includes 2 patients in Stage 0. and numbers 13 and 14 represent intrapulmonary lymph nodes. Results Of 1,654 patients undergoing resection, 1,389 (84%) had dissection of mediastinal lymph nodes and 265 (16%) did not. Staging of patients who had dissection of the mediastinal lymph nodes was as follows: 576 in Stage I, 110 in Stage 11, 532 in Stage 111, and 171 in Stage N. For the patients who did not have dissection of mediastinal lymph nodes, staging was as follows: 41 in Stage I, 3 in Stage 11, 116 in Stage 111, and 105 in Stage IV. The percentage of patients with an advanced lesion was higher in the group without dissection. The 265 patients without dissection had a lower 5-year survival than the 1,389 patients with dissection, 9.7% and 41.3%, respectively. Patients in Stages I and I1 survived for more than 5 years, even in the group without mediastinal node dissection. However, for Stage 111 patients, which included patients with mediastinal metastasis, only 5.1% of 116 patients without dissection of the mediastinal lymph nodes survived 5 years compared with 23.8% of 532 with mediastinal dissection (Table 2). The 1,654 patients having resection were divided into M (metastasis) categories: 1,378 were MO and 276, M1. The 5-year survival for the 1,378 MO patients based on lymph node metastasis was as follows: 59.3%, NO MO; 36.8%, N1 MO; and 14.0%, N2 MO. The 5-year survival for the 276 M1 patients was 6.9% (Fig 1). Of the 648 patients in Stage 111, 426 were classified as N2 MO. Mediastinal lymph node dissection was performed in 345 of these N2 MO patients and was not done in 81. The overall 5-year survival for the 345 patients with lymph node dissection was 15.9%. It was 30.0% for the 50 T1 N2 MO patients, 14.5% for the 169 T2 N2 MO patients, and 12.9% for the 126 T3 N2 MO patients. The overall 5-year survival for the 81 patients without dissection was 6.7%. None of the 6 T1 N2 MO patients survived 5 years, and 3.7% of the 29 T2 N2 MO patients and 10.2% of the 46 T3 N2 MO patients lived 5 years (Table 3). Of the 426 patients classified as N2 MO, 242 underwent a curative operation in which pulmonary resection Months After Resection Fig 1. lnpuence of lymph node metastases and distant metastases on survival after lung resection. with complete mediastinal lymph node dissection was done and no gross tumor remained. Another 103 underwent a palliative operation in which pulmonary resection with mediastinal lymph node dissection was performed though tumor remained macroscopically or microscopically. The remaining 81 patients had pulmonary resection without mediastinal lymph node dissection as a palliative operation. The survival of the patients with mediastinal lymph node metastasis who underwent a curative operation was 19.2%. The survival of the patients who underwent a palliative operation with mediastinal lymph node dissection was 7.9%, and for patients who underwent a palliative operation without mediastinal lymph node dissection, survival was 6.7% (Fig 2). Based on histological classification, survival in the N2 MO group having a curative operation was 30.8%, 16.0%, 12.8%, and 0% for squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and adenosquamous cell carcinoma, respectively. Survival of patients with squamous cell carcinoma was better in any T

4 606 The Annals of Thoracic Surgery Vol46 No 6 December 1988 Table 3. Prognosis following Mediastinal Lymph Node Dissection for N2 Non-Small Cell Lung Cancer 5-Year Survival With Dissection Without Dissection No. of % % Total Surviving TNM Patients No. surviving No. surviving (%) T1 N2 MO T2 N2 MO T3 N2 MO Total >.- c---. curative ( n = 242) t.~palliative with L.N.d~ssection (n= 103) e---+ palliative without L.N. dissection (n= 81) these 11 patients was palliative were as follows: a bronchial stump or a stump of blood vessel was identified microscopically as being positive for residual tumor in 6 patients; there was incomplete mediastinal lymph node dissection in 3; intrapulmonary metastasis was identified microscopically within the resected lobe in 1 patient; and lung cancer was combined with pleural dissemination of long standing in 1. All 11 patients received postoperative adjuvant therapy-radiation therapy, chemotherapy, or both (Fig 3). V I I j---*---: Months After Resection Fig 2. Comparison of survival between cases with and without dissection of mediastinal lymph nodes (LN). (tumor) category than it was for patients with other types of histology (Table 4). There were 35 absolute 5-year survivors in the N2 group who underwent operation. Of these 35 patients, a curative operation was performed in 24 patients and 11 underwent a palliative operation. Two of the 11 patients (Patients 29 and 32) were treated with sampling of metastatic mediastinal lymph nodes only, 3 (Patients 30, 31, and 35) had an incomplete mediastinal lymph node dissection, and 6 underwent complete mediastinal lymph node dissection. The reasons the operation in ' ' 67 Comment Complete surgical excision of cancer by lobectomy or pneumonectomy combined with mediastinal lymph node dissection is the standard procedure for lung cancer operations, and is defined as a radical resection or a curative operation when no residual tumor remains after operation. Pulmonary resection without mediastinal lymph node dissection or pulmonary resection with residual tumor remaining after operation is a palliative operation [15]. Mediastinal lymph node dissection was not performed in 18% of all patients in Stage 111. For the majority of these patients, it was not done because they had advanced cases of lung cancer and the practicality of a curative operation was not assessed at the time when mediastinal lymph node dissection would have been combined with resection. In the remaining patients, dissection was not done for several reasons, such as the age of the patient, the poor risk status of the patient because Table 4. Survival of Patients who Underwent Resection for N2 Lesion Based on Histological Classifkation 5-Year Survival Squamous Cell Adenocarcinoma Large Cell Adenosquamous TNM No. of % % % % Total Surviving Categog Patients No. Survival No. Survival No. Survival No. Survival (%) TlN2MO T2N2MO T3N2MO Total

5 607 Naruke et ak Non-Small Cell Carcinoma of the Lung with Metastasis R U Lobectomy Adenoca Rad tchemoth R U Lobectomy Adenoca B A l R. U. Lobectomy No Adjuvant R. Pneumonectomy L. Pneumonectomy B. A. I. R. Pneumonectomy Chemoth. No Adjuvant M L. U. Lobectmy Cur at i ve NO Adjuvant R. Pneumonectomy R. U. Lobectomy Cur at i ve Large Cell ca. Chemo th. No Adjuvant A. I. t 20 R. U. Lobectomy Chemot R. Pneumonectomy B. A. I. Chemoth No Adjuvant B. C. G. -kchemoth. B. C. G. tchemoth. R. M. L Lobectomy Squaws ca. No. Adjuvant No. Adjuvant R. U. Lobeltomy L U. Lktomy L Pneurnonectomy No. Adjuvant No. Adjuvant SSuaWS B. A. 1.fChemoth. L. L. Lobectomy (Bronchial stump) Chemot L. Pneumonectomy (PVstump) B. A. I. S R U M-Lobectomy (Incwete mediast mde dissectim) Adeooca Rad tchemth R. Pneumonectomy (Pleural Dissemination) (Incomplete mediast. node dissection) B. C G. tchemoth. Large cell B. C. G. SChemoth. (Incomplete mediast. node dissection) R. U. M. kctomy (3a-h) brge cell t Chemoth. R. U. Lobectmy (Bronchial stump) Squarnous ca. (Bronchial stump) L. Pneumonectomy (PA stump) L Rewronectomy (Incomdete surgicd margin) Squams ca. B. A. I.tCherno. Fig 3. Summary of dnta on 35 patients with N2 disease who survived for 5 years or more. (RU = right upper; = radiation therapy; Chemoth. = chemotherapy; BAI = bronchial artery infusion of antitumor agent; R = right; L = left; RL = right lower; LU = left upper; RML = right middle and lower; LL = left lower; PV = pulmonary vein; RUM = right upper and middle; PA = pulmonay artery; 3a -k pm = anterior mediastinal lymph node and intrapulmonary metastasis; BCG = bacillus Calmette-Gukrin.) of complications, or technical reasons (administration of preoperative radiation therapy or chemotherapy). In general, however, we combine pulmonary resection with mediastinal lymph node dissection for the surgical treatment of lung cancer. For Stage III patients, the 5-year survival of those confirmed to be N2 by thoracotomy was 14.0%, and of these patients, the survival of select patients who had a curative operation was 19.2%. The presence of metastasis to mediastinal lymph nodes is identified by pathological examination of dissected lymph nodes or by mediastinoscopy or mediastinotomy. Radiography, including tomography, computed tomography, bronchial arteriography, and radioisotope scanning, is used to diagnose metastasis to mediastinal lymph nodes. These are, however, indirect diagostic techniques for assessing the presence of metastasis to mediastinal lymph nodes by identifymg the size of lymph nodes or an abnormality in perfusion. They do not directly determine the presence of the metastasis itself. When surgical treatment of lung cancer with

6 608 The Annals of Thoracic Surgery Vol46 No 6 December 1988 mediastinal lymph node involvement is discussed, one of the long-standing problems has been to determine whether staging should be done by mediastinoscopy or thoracotomy. The problem derives from the fact that the prognosis for patients, in whom metastases were diagnosed by mediastinoscopy, has been poorer; and in general, they have had advanced disease compared with patients in whom metastases were identified by pathological examination of lymph nodes dissected at thoracotomy. For patients with metastases to mediastinal lymph nodes confirmed by mediastinoscopy, the best 5-year survival reported to date is 18% (81 and the latest figure reported of which we are aware is 9% [lo]. On the other hand, for patients in whom positive mediastinal lymph nodes were proven at thoracotomy, survival was from 19 to 29% [ Martini and associates [ll] reported that there has not been a significant difference in the postoperative prognosis for patients with lung cancer with mediastinal lymph node metastases between patients with squamous cell carcinoma and those with adenocarcinoma. However, since the results of treatment are particularly good for squamous cell carcinoma [7, 9, 10, 12, 14, 17, the view supporting operative intervention for squamous cell carcinoma with ipsilateral mediastinal lymph node metastasis is dominant. It was reported by Bergh and Schersten [l], Paulson and Reisch [4], Smith [6], and Matsubara (17 that there is a difference in the prognosis for patients with lung cancer between the intranodal type of mediastinal lymph node metastasis and the perinodal type. However, based on the end results in our experience [18], some patients with mediastinal lymph node metastases had a long survival even when metastases had invaded perinodal tissue, and on the other hand, some patients with the intranodal type had a poor prognosis. Therefore, we believe operation is indicated in patients for whom a curative operation with complete dissection of mediastinal lymph node metastases is applicable. Furthermore, among the patients in whom metastasis to pulmonary lymph nodes was noted at the time of operation, some (24.2%) had metastasis to mediastinal lymph nodes, or "skipping" metastasis. Consequently, we believe it necessary to perform dissection of mediastinal lymph nodes even for patients in whom no metastasis to pulmonary lymph nodes is identified at operation [19]. The need for operation has been determined without mediastinoscopy at the National Cancer Center Hospital. The percentage of patients with lung cancer undergoing resection not dependent on assessment by mediastinoscopy was 90% ( ) in the period 1962 through 1975, 95% (309/325) in the period 1976 through 1979, and 96% (904/937) from 1980 to These data suggest that mediastinoscopy is not necessary to determine or assess resectability. At the same time, mediastinoscopy or dissection of the mediastinum can be worthwhile to see if there is the possibility of a curative operation. Since 1981, for patients with squamous cell carcinoma of the left lung, in whom metastases to subcarinal or tracheobronchial lymph nodes are confirmed at thoracotomy, we perform dissection of the contralateral mediastinum through a median stemotomy when a curative operation is considered possible. Though there have not been enough of these patients to evaluate the end results, some had a long survival. The need to add dissection of the contralateral mediastinal lymph nodes for patients with squamous cell carcinoma of the left lung should be further evaluated. Curability, the prognosis, and risks arising from dissection should be taken into consideration. As for combined therapy for patients with positive mediastinal lymph node metastases, Kirsh and Sloan (91 emphasized that postoperative radiation therapy was effective. We [5] have not been able to verify the influence of adjuvant therapy in patients with N2 disease in whom a curative operation was performed. However, based on the results in patients treated with a palliative procedure, adjuvant therapy was effective for them. In particular, radiation therapy was effective in those patients who had squamous cell carcinoma with a microscopically positive surgical margin. We currently are trying to determine when curative operation is indicated to improve local curability in as many instances as possible. Supported in part by a grant-in-aid for cancer research from the Ministry of Health and Welfare, Japan. References 1. Bergh NP, Schersten T Bronchogenic carcinoma: a follow- up study of a surgically treated series with special reference to the prognostic sigruficance of lymph node metastases. Acta Chir Scand [Suppl] 1347, Gibbon JRl? The value of mediastinoscopy in assessing operability in carcinoma of lung. Br J Dis Chest 66:162, Shields TW, Yee J, Conn JH, Robinette CD: Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma. Ann Thorac Surg 20501, Paulson DL, Reisch JS Long-term survival after resection for bronchogenic carcinoma. Ann Surg 184:324, Naruke T, Suemasu K, Ishikawa S Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg 76832, Smith RA: The importance of mediastinal lymph node invasion by pulmonary carcinoma in selection of patients for resection. Ann Thorac Surg 25.5, Rubinstein I, Baum GL, Kalter Y, et ak Resectional surgery in the treatment of primary carcinoma of the lung with mediastinal lymph node metastases. Thorax 3433, Kirschner PA Lung cancer: preoperative radiation therapy and surgery. NY State J Med 198:339, Kirsh MM, Sloan H Mediastinal metastases in bronchogenic carcinoma: influence of postoperative irradiation, cell type, and location. Ann Thorac Surg 33:459, Pearson FG, Delarue NC, Ilves R, et ak Significance of positive superior mediastinal nodes identified at mediastinos-

7 609 Naruke et a1 Non-Small Cell Carcinoma of the Lung with Metastasis copy in patients with resectable cancer of lung. J Thorac Cardiovasc Surg 83:1, Martini N, Flehinger BJ, Zaman MB, et al: Results of resection of non-oat cell carcinoma of the lung with mediastinal lymph node metastases. Ann Surg , Hitomi S, Taki T Surgical indication and limitation of pulmonary cancer from the viewpoint of lymph node metastasis. Chest Surg 38351, 1985 (in Japanese) 13. Suemasu K, Ri T, Sawamura K, et al: Analysis of end results of N2 cases undergoing operation with dissection of mediastinal lymph nodes by data collected from 7 institutions, part of a study on multidisciplinary treatment of lung cancer. Lung Cancer 26:489, Nishiyama S, Sawamura S, et al: End results of operated stage 111 cases (P-N2) of lung cancer. Lung Cancer 26:489, The Japan Lung Cancer Society: General Rule for Clinical and Pathological Record of Lung Cancer. Tokyo, Kanehara, Pearson FG: Management of Stage I11 disease: mediastinal adenopathy-the N2 lesion. In Delarue NC, Eschapasse H (eds): International Trends in General Thoracic Surgery: Lung Cancer. Philadelphia, Saunders, 1985, vol 1, pp Matsubara Y: N-factor in the surgical treatment of lung cancer in relation to mediastinoscopy and to the presence of anti-tumor specific antibody in mediastinal lymph nodes. Chest Surg 32487, Suemasu K, Naruke T: Prognostic significance of extranodal cancer invasion of mediastinal lymph nodes in lung cancer. Jpn J Clin Oncol12:207, Naruke T Lymph node metastasis of lung cancer. In Ishikawa S (ed): Cancer of the Lung; Diagnosis and Treatment. Tokyo, Kodansha, 1983, vol3, pp Invited Comment There is benefit from resection in patients with carcinoma of the lung despite the presence of mediastinal nodal involvement. Long-term survival of at least 5 years after resection can be attained in 20 to 30% of these patients. This is of particular significance as nearly 50% of all lung cancers have mediastinal lymph node metastases at presentation. My colleagues and I concur with Naruke and associates views that, for resection to be effective and potentially curative, it must be complete and include a mediastinal lymph node dissection and not mere node sampling for staging purposes. To jushfy the surgical treatment, resection must be offered to good-risk patients who can tolerate the procedure with minimal morbidity. We also concur with Dr. Naruke and his co-workers view that patients with peripheral tumors and N2 disease who present with an apparent normal mediastinum on plain chest roentgenograms generally have resectable tumors. We do not perform mediastinoscopy in this group of patients but recommend thoracotomy instead for resection and staging. Computed tomographic (CT) scanning has become an integral part of the staging and preoperative evaluation of the mediastinum. New-generation scanners are now capable of detecting enlarged paratracheal nodes greater than 1 cm in diameter. CT scanning has been less accurate in detecting enlarged subca- Mal nodes or in assessing the mediastinum when the lung tumor is central, making it difficult to distinguish T3 from N2 disease. A normal mediastinum shown by CT scanning is extremely helpful and indicative of high resectability. The presence of discrete enlarged nodes in the ipsilateral upper medias- tinum, in the aorticopulmonary window, or in the subcarinal region usually suggests encapsulated nodes with intranodal disease. These nodes may be readily excisable. Therefore, the importance of CT scanning, we believe, is to identify contralateral mediastinal disease, involvement in multiple levels of nodes, and invasion of mediastinal structures by nodal disease. It is becoming increasingly evident that lymph node dissection not only provides accurate staging information but can allow the encompassing of all disease in some patients, with a resultant improved survival rate. We believe that the gold standard for complete resection in lung carcinoma must be the inclusion of a formal mediastinal lymph node dissection with every resection. However, we have not extended the use of regional lymph node dissection to contralateral mediastinal nodes via a sternotomy in patients with N2 disease. There is no evidence as yet that there is improved survival yielded by surgical treatment in patients with contralateral nodal involvement. In this group of patients with N3 disease as well as in those presenting with bulky ipsilateral N2 metastases, we prefer to use neoadjuvant chemotherapy. Nael Martini, M.D. Memorial Sloan-Kettering Cancer Center 1275 York Ave New York, NY Every surgeon who has had the pleasure of seeing lung cancer patients return for follow-up 5 years after resection that included systematic dissection of positive mediastinal lymph nodes believes, at some level, that dissection of these nodes must have influenced outcome. Radical dissection (radix [root], dissecure [to cut away]) was Halsted s great contribution to cancer surgery, thereby reducing the local recurrence rate of the bulky ulcerating T3 breast cancers of his day from 80 to 6%. His mastectomy has been reviled in an era of T1 lesions discovered by mammography because surgeons have persevered too long in their belief in the second component of the operation-the radical resection of draining axillary nodes to prevent local and systemic recurrence. The randomized trials of the National Surgical Adjuvant Breast Cancer Program have clarified the role of radical mastectomy. There is universal agreement that radical resection is ap propriate when required for local control of the T factor. Systematic dissection of draining nodes has not proved superior to node sampling for staging purposes. Perhaps this is because the systemic therapy available in breast cancer is so effective that it obscures the real or imagined benefit of axillary dissection, or perhaps the axillary chain is not really a dissectable root of the cancer, but a set of real or potential metastases. Is systematic lymph node dissection ever an effective therapeutic intervention? Belief in its efficacy is widespread and the technique is applied in many types of cancer. Rigorous proof of efficacy is not available for any of them, however. This does not prevent me from performing systematic mediastinal lymph node dissection, but it is only fair to admit that the rational basis for systematic mediastinal lymph node dissection is not secure. Support for this policy comes from reports in the literature, cited by Dr. Naruke and colleagues, that dissection of positive mediastinal nodes discovered at thoracotomy may be associated with 5-year survival rates as high as 29 or 34% in some lung cancer subsets. Like many surgeons, I do mediastinal lymph node sampling to rationalize segmental resection in

8 610 The Annals of Thoracic Surgery Vol46 No 6 December 1988 cases of limited disease, and I perform a North American-style systematic lymphadenectomy, probably less complete than Dr. Naruke s, in the belief that it will enhance the curative potential of lobectomy or pneumonectomy in patients with more extensive disease. These procedures are performed in patients selected for resection because of negative findings from computed tomography or mediastinoscopy. I accept this widely practiced treatment policy knowing that it is based more on feelings than reason. Dr. Naruke takes a much stronger position, which requires careful analysis. He performs a Japanese systematic lymphadenectomy, a very complete and meticulous dissection that may extend the time of operation to 8 hours or more. He offers this treatment to Stage IV patients with distant metastases as well as to those in Stage 111, 11, and I, in the belief that this component of the procedure has its own therapeutic benefit. The series he reports does not justify the conclusion stated in the abstract and implied by Tables 2 and 3 that lymphadenectomy should be performed whenever possible to improve end results. It is clear that patients undergoing lymphadenectomy had a higher survival rate than control group patients who were denied systematic lymphadenectomy because they were considered too ill or to have disease that was too advanced to justify lymphadenectomy. This selection shows good judgment and has yielded excellent results, but it does not serve to rationalize systematic lymphadenectomy. The use of adjuvant chemotherapy and radiotherapy in the patients in Naruke and associates series, though more minor confounding variables than selection bias, further confuses the assessment of lymphadenectomy. Is this formidable extension of surgical resection appropriate and beneficial? Which patients, if any, should be offered systematic lymphadenectomy? At this point in the evolution of lung cancer treatment when surgical intervention continues to offer the best and perhaps only effective treatment and when adjuvant irradiation and chemotherapy have a minimal effect on survival, it seems reasonable to evaluate Dr. Naruke s approach to systematic mediastinal lymphadenectomy in a carefully controlled, randomized, prospective trial. The North American Lung Cancer Study Group is an appropriate instrument for conducting such a trial. Although the survival rate of lung cancer patients has not improved substantially over the past several decades, the quality of residual life has improved because the incidence of nonresecting or unhelpful thoracotomy has been reduced to less than 10%. Dr. Naruke s policy implies that we should perform more thoracotomies with potentially more morbidity resulting from extended intrathoracic lymph node dissections. It is incumbent on us to subject this policy to the same scientific scrutiny that has been applied to radical mastectomy before it can be recommended as standard treatment. Until the evidence is in from such a study, I believe we must accept the Scottish verdict of not proven for the therapeutic efficacy of systematic lymphadenectomy. Martin F. McKneally, M.D., Ph.D. Division of Cardio-Thoracic Surgery The Albany Medical College 701 Medical Education Building Albany, NY 12208