Results of Operation Without Adjuvant Therapy in the Treatment of Small Cell Lung Cancer Samir S. Shah, MBBS, Joao Thompson, MD, and Peter Goldstraw, FRCS Department of Thoracic Surgery, Royal Brompton National Heart & Lung Hospitals, London, England
The rolle of surgery in the treatment of small cell lung cancer remains a subject of debate. We carried out a retrospective review of 87 patients with small cell lung cancer referred to one surgeon for staging and treatment. Thirty patients (34.5%)were deemed suitable for thoracotomy. Fourteen patients had stage I disease, 5 patients had stage I1 disease, and 11 patients had stage 1x1 disease. Twentyeight of the 30 patients (93.3%)went on to have surgical resection. The actual overall 5-year survival in
all patients who underwent thoracotomy was 43.3%.The actual 5-year survival for patients in stages I and 1x1 was 57.1%and 55.5%, respectively. No patients with stage XI disease survived 5 years. We conclude that there is a small group of patients with small cell lung cancer in whom, with careful preoperative staging, the prospects of cure by operation are similar to those with non-small lung cancer. (Ann Thorac Surg 1992;54:498-501)
S
the brain, chest, and abdomen. Mediastinoscopy, and left anterior mediastinotomy if the tumor was located in either the left upper lobe or the left main bronchus, completed the staging process. In the patients in whom the diagnosis of SCLC was made before thoracotomy, a radioisotope bone scan and a bone marrow investigation were performed routinely.
mall cell lung cancer (SCLC) accounts for 19% to 22% of all bronchial carcinomas [l].At presentation, approximately two-thirds of patients have extensive disease, often with clinical evidence of metastases, and many are too ill to benefit from any form of therapy other than supportive care. The remaining one-third have so-called limited disease confined to one hemithorax and the ipsilateral supraclavicular fossa [2, 31. In this latter group the tumor is usually far too extensive to be considered amenable to operation, and primary treatment consists of chemotherapy. A small proportion of patients with SCLC have extremely localized disease. This group is important because for these patients the prospects of operation and cure are good. The aim of this report is to analyze the results of surgical intervention in patients with small cell lung cancer at the Royal Brompton National Heart and Lung Hospital over a 7-year period. All operations were conducted by a single surgical team using a uniform staging protocol.
Material and Methods We undertook a retrospective review of all cases of carcinoma of the lung seen by one surgeon (P.G.) in the period 1'380 to 1987. During the period of investigation, 87 patients with the diagnosis of SCLC were referred for staging and treatment. All patients underwent careful history and clinical examination. Routine blood tests included a full blood count, liver function tests, and serum calcium determinations. In addition, each patient had a chest radiograph and bronchoscopy. Those still considered to have operable disease proceeded to computed tomographic scan of Accepted for publication Feb 24, 1992. Address re,>rint requests to Dr Shah, Department of Thoracic Surgery, Royal Brompton National Heart & Lung Hospitals, Sydney St, London SW3 6NP, England.
0 1992 by The Society of Thoracic Surgeons
Results After preoperative staging, 30 patients (34.5%) were considered to have resectable disease and 57 patients (65.5%) were considered to have inoperable disease due to mediastinal lymph gland involvement or evidence of distal metastases. The male to female ratio was 19:11 and the age range was 39 to 77 years (mean, 58 years). In 18 of these 30 patients the diagnosis of SCLC was made before operation by either bronchoscopy and biopsy or transcutaneous needle biopsy. Ten patients had the diagnosis made at the time of operation. In 2 patients the records were not clear as to whether the diagnosis was made before or at the time of the operation. The bone scans and bone marrow biopsies performed as a routine in patients with a preoperative diagnosis of SCLC were negative in all cases. At thoracotomy, 28 patients (93.3%) went on to a resection and 2 patients (6.7%), both with stage I11 disease, were found to have nonresectable disease. Of the patients who underwent resection, 14 had pneumonectomies (50.0%), 9 had lobectomies (32.1%), 3 had sleeve resections (10.7%), 1 had bilobectomy (3.3%), and 1 had wedge resection (3.3%). There were no postoperative deaths. The tumor was in a central position in 14 patients (46.7%) and peripheral in 16 patients (53.3%). According to the international TNM staging classification [4], after operation 14 patients (46.7%) had stage I disease (T1 NO MO, 8 patients; T2 NO MO, 6 patients), 5 patients (16.7%) had stage I1 disease (TI N1 MO, 1 patient; T2 N1 MO, 4 0003-4975/92/$5.00
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
Ann Thorac Surg 1992;54:49%501
499
Fig 1. Actual 5-year survival after operation for ' small cell lung cancer.
% Survival
--R
-Stage
1
+Stage
2
+Stage
3
+-Overall
Survival
patients), and 11 patients (36.7%)had stage I11 disease (T3 NO MO, 8 patients; T3 N1 MO, 1 patient; T3 N2 MO, 2 patients). Although many of the patients were treated in conjunction with our oncological colleagues, none of the patients received adjuvant therapy. The survival data in our patients are shown in Figure 1. The actual overall 5-year survival in the patients who underwent thoracotomy was 43.3%. Actual survival with respect to the stage of the disease showed that the 5-year survival for stage I was 57.1% and stage I11 was 55.5%. No patients with stage I1 disease survived 5 years. Survival with respect to the node status of the patients is shown in Figure 2. There were 22 patients and 6 patients with NO and N1 disease, respectively. The 2 patients who were found to have inoperable disease both had evidence of N2 disease at operation. The actual 5-year survival for patients with NO disease was 59.1%. No patients with N1 disease survived 5 years. The 5-year survival was 42.8% in patients with a centrally located tumor compared with 50.0% in those with a peripherally located tumor.
Comment Small cell lung cancer is a highly malignant tumor with particular cellular and histopathological characteristics.
The clinical features include a rapid growth rate with a short doubling time [5], a propensity for early metastases via lymphatic and hematological spread, and dramatic response to chemotherapy, with a very short survival time in patients who are not subjected to any treatment. Without any therapy the median survival in one group of patients was 2.8 months after diagnosis [6]. By 1970, operation in SCLC had been abandoned as primary treatment due to the overall poor prognosis-5-year survival rates ranging from 2.5% to 21.4% [7-lo]. In an attempt to clarify the matter, the Medical Research Council of Great Britain [ l l ] carried out a prospective comparative trial in which patients with SCLC were subjected to either surgical resection (71 patients) or radiation therapy (73 patients). Of the surgical group only l patient, who went on to refuse operation, survived 5 years. With the advent of effective cytotoxic agents, it became clear that SCLC was sensitive to chemotherapy, and this became the mainstay of therapy. Several studies reported rates of complete remission as high as 70% to 90% of the cases in patients with limited disease. Although combination chemotherapy produced encouraging figures in terms of remission, few patients achieved long-term survival. In patients with limited disease the median survival rate was 14 months compared with 9 months for those
% Survival
Fig 2. Actual 5-year survival versus node status after operation for small cell lung cancer.
-
40
30 -
20 10
~
0
1
-NO Disease
2
3
4 4
Years +N1
Disease
+-
Overall Survival
5
500
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
patients with more extensive disease [12-141. In a longitudinal study reporting the results in 3,681 patients with SCLC, Souhami and Law [15] found that current treatment resulted in a 2-year survival of 8.5% and 2.2% for those with limited and extensive disease, respectively, and an overall 2-year survival of 5.9%. Chemotherapy was effective in eradicating the occult disease but not the primary tumor. Recurrences were often within the thorax [16, 171. Irradiation was used either concurrently or as an adjunct to chemotherapy to overcome this problem. The results were disappointing, most trials concluding that radiotherapy did not result in any substantial decrease in the incidence of recurrence [1&23]. In 19:’5, the Armed Forces Asymptomatic Pulmonary Nodule Study published results showing that the 5-year survival of patients after resection of nodules containing SCLC was the same as that of other cell types [24]. Subsequently, results from other studies suggested that the total rejection of operation as a treatment option may have been premature [25]. These findings, coupled with the failuire of chemotherapy and radiotherapy in markedly improving prognosis, revived interest in the role of surgical resection in the management of SCLC. Clearly, accurate preoperative staging is especially important in SCLC if one is to avoid unnecessary operations. In our group 93.3% of the patients with SCLC selected for operation went on to have a resection performed, which is a figure that is comparable to our experience with nonsmall cell carcinoma of the lung [26]. Furthermore, it is now generally agreed that patients who have T4/N2-3 disease are not suitable for operative management. It is therefore very important that patients have meldiastinoscopy or mediastinotomy before thoracotomy, in addition to other routine preoperative investigations [27]. This contrasts with our strategy in patients with nor\-small cell lung cancer, in whom we have adopted a selective approach to mediastinoscopy based on the findings of a computed tomographic scan of the thorax. We have not assumed this to apply in SCLC, and mediastinal exploration is routinely performed if the diagnosis is, known preoperatively [28]. Routine bone marrow examination, however, in this series did not reveal any evidence of metastatic disease. This would suggest that this investigation need no longer be a part of preoperative staging [29]. Many authors consider the TNM staging system irrelevant in the classification of small cell lung cancer and restrict staging categories to two g r o u p s t h o s e with limited disease (tumor that is confined to one hemithorax, sometimes including ipsilateral nodes, but restricted to one radiation field) and those with extensive disease (all patients beyond these boundaries) [25]. In our series, we found that with precise preoperative and postoperative staging the TNM classification provided useful information about survival. In 1985, Davis and associates [30] surveyed all longterm survivors of small cell carcinoma within a specified population. This study stated that once the stage of the disease was taken into account, the only factor relating to
Ann Thorac Surg 1992;54:49%501
survival beyond 2 years was whether the patient received operation as the first line of treatment. Furthermore, within a particular stage, those patients who did not receive operation were subject to a fourfold increase in the risk of death compared with those who did. Prasad and co-workers [31] argue that many patients are denied operation because there are physicians who consider small cell lung cancer as a nonsurgical disease. Recently the role of operation has been reconsidered in combination with adjuvant therapy. Preliminary results reported by Karrer and co-workers [32, 331 state that for stage I and 11, operation should be followed by chemotherapy and radiotherapy, whereas for stage I11 disease debulking chemotherapy should be given and adjuvant operation should be considered in those patients who respond. Unfortunately these studies do not have a control arm, and our study demonstrates that equally good results can be achieved with operation alone in a carefully selected group of patients. In our series the actual overall 5-year survival for patients with small cell carcinoma who underwent resection was 43.3%, which compares favorably with other series in which patients received adjuvant therapy in addition to operation [25, 341. It is important for all who treat this usually fatal condition to remain alert for the rare patient who may benefit from operation. In the case of these fortunate few patients the prospects of surgical cure are similar to those for non-small cell carcinoma of the lung [35]. We thank Ms Sally Jordan for her help in the preparation of the manuscript.
References 1. Katlic M, Carter D. Prognostic implications of histology, size and location of primary tumors. Prog Cancer Ther 1979;ll: 143-50. 2. Crompton G. Small cell lung cancer [Editorial]. Br Med J 1990;300:209-10. 3. Mountain CF. Operation for small cell carcinoma revisited [Editorial]. J Clin Oncol 1987;5:687-8. 4. Mountain CF. A new international staging system for lung cancer. Chest 1986;89:225=3S. 5. Chahinian P. Relation between tumor doubling time and anatomoclinical features in 50 measurable pulmonary cancers. Chest 1972;61:340-5. 6. Maassen W, Greschuchna D. Small cell carcinoma of the lung-to operate or not? Surgical experience and results. Thorac Cardiovasc Surg 1986;34:71-6. 7. Siddons AH. Cell type in the choice of cases of carcinoma of the bronchus for surgery. Thorax 1962;17308-9. 8. Taylor AB, Shinton NK, Waterhouse JA. Histology of bronchial carcinoma in relation to prognosis. Thorax 1963;18: 178-81. 9. Goldman KP. Histology of lung cancer in relation to prognosis. Thorax 1965;20:298-302. 10. Lennox SC, Flavell G, Pollock DJ, et al. Results of resection for oat-cell carcinoma of the lung. Lancet 1968;2:925-7. 11. Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus. Tenyear follow-up. Lancet 1973;2:63-5. 12. Johnson DH, Greco FA. Small cell carcinoma of the lung. CRC Crit Rev Oncol Hematol 1986;4:303-36.
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
Ann Thorac Surg 1992;54:49%501
13. Hande KR, Des Prez RM. Current perspectives in small cell lung cancer. Chest 1984;85:669-77. 14. Aisner J, Albert0 P, Bitran J, et al. Role of chemotherapy in small cell cancer: a consensus report of the international association for the Study of Lung Cancer workshop. Cancer Treat Rep 1983;673743. 15. Souhami RL, Law K. Longevity in small cell lung cancer. A report to the Lung Cancer Subcommittee of the United Kingdom Coordinating Committee for Cancer Research. Br J Cancer 1990;61:584-9. 16. Greco FA, Johnson DH, Hainsworth JD, et al. Chemotherapy of small cell lung cancer. Semin Oncol 1985;11:31-7. 17. Spiro SG. Chemotherapy for small cell lung cancer [Editorial]. Br Med J (Clin Res) 1985;290:413-4. 18. Lichter AS, Bunn PA Jr, Ihde DC, et al. The role of radiation therapy in the treatment of small cell lung cancer. Cancer 1985;55:2163-75. 19. Perez CA, Einhom L, Oldham RK, et al. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol 1984;2: 120c-8. 20. Johnson RE, Brereton HD, Kent CH. "Total" therapy for small cell carcinoma of the lung. Ann Thorac Surg 1978;25: 51&5. 21. Souhami RL, Geddes DM, Spiro SG, et al. Radiotherapy in small cell cancer of the lung treated with combination chemotherapy: a controlled trial. Br Med J (Clin Res) 1984;288: 16434. 22. Byhardt RS, Cox JD, Libnoch JA, Komaki R, Holoye PY, Anderson T. Multiagent chemotherapy, prophylactic neuroaxis irradiation and consolidative irradiation for small cell carcinoma of the lung. Ann J Clin Oncol 1985;8:504-11. 23. Mira JG, Livingston RB, Moore TN, Chen T, Batley F. Influence of chest irradiation in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study. Cancer 1982;50:126&72. 24. Higgins GA, Shields TW, Keehan RJ. The solitary pulmonary
25. 26. 27. 28. 29. 30. 31. 32. 33.
34.
35.
501
nodule. Ten-year follow-up of Veterans Administrationarmed forces cooperative study. Arch Surg 1975;110:570-5. Shields TW, Higgins GA Jr, Matthews MJ, Keehn RJ. Surgical resection in the management of small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1982;84:481-8. Gaer JA, Goldstraw P. Intraoperative assessment of nodal staging at thoracotomy for carcinoma of the bronchus. Eur J Cardiothorac Surg 1990;4:207-10. Sridhar KS, Hussein AM, Thurer RJ. Evolving role of surgical treatment in limited-disease small cell lung carcinoma. J Surg Oncol 1989;40:155-61. Goldstraw P, Kurzer M, Edwards D. Pre-operative staging of lung cancer: accuracy of computed tomography versus mediastinoscopy. Thorax 1983;38:10-5. Campling B, Quirt I, DeBoer G, Feld R, Shepherd FA, Evans WK. Is bone marrow examination in small-cell lung cancer really necessary? Ann Intern Med 1986;105:508-12. Davis S, Wright PW, Schulman SF, Scholes D, Thorning D, Hammer S. Long-term survival in small cell carcinoma of the lung: a population experience. J Clin Oncol 1985;3:80-91. Prasad US, Naylor AR, Walker WS, Lamb D, Cameron EW, Walbaum PR. Long term survival after pulmonary resection for small cell carcinoma of the lung. Thorax 1989;44:784-7. Karrer K. Rationale for surgery as the first step in the multimodality treatment of small cell lung cancer (SCLC). J Chemother 1989;1:147-50. Karrer K, Shields TW, Denck H, Hrabar 8, Vogt-Moykopf I, Salzer GM. The importance of surgical and multimodality treatment for small cell bronchial carcinoma. J Thorac Cardiovasc Surg 1989;97168-76. Shepherd FA, Ginsberg RJ, Evans WK, et al. Reduction in local recurrence and improved survival in surgically treated patients with small cell lung cancer. J Thorac Cardiovasc Surg 1983;86:498-506. Deneffe G, Lacquet LM, Verbeken E, Vermaut G. Surgical treatment of bronchogenic carcinoma: a retrospective study of 720 thoracotomies. Ann Thorac Surg 1988;45:38&3.
The rolle of surgery in the treatment of small cell lung cancer remains a subject of debate. We carried out a retrospective review of 87 patients with small cell lung cancer referred to one surgeon for staging and treatment. Thirty patients (34.5%)were deemed suitable for thoracotomy. Fourteen patients had stage I disease, 5 patients had stage I1 disease, and 11 patients had stage 1x1 disease. Twentyeight of the 30 patients (93.3%)went on to have surgical resection. The actual overall 5-year survival in
all patients who underwent thoracotomy was 43.3%.The actual 5-year survival for patients in stages I and 1x1 was 57.1%and 55.5%, respectively. No patients with stage XI disease survived 5 years. We conclude that there is a small group of patients with small cell lung cancer in whom, with careful preoperative staging, the prospects of cure by operation are similar to those with non-small lung cancer. (Ann Thorac Surg 1992;54:498-501)
S
the brain, chest, and abdomen. Mediastinoscopy, and left anterior mediastinotomy if the tumor was located in either the left upper lobe or the left main bronchus, completed the staging process. In the patients in whom the diagnosis of SCLC was made before thoracotomy, a radioisotope bone scan and a bone marrow investigation were performed routinely.
mall cell lung cancer (SCLC) accounts for 19% to 22% of all bronchial carcinomas [l].At presentation, approximately two-thirds of patients have extensive disease, often with clinical evidence of metastases, and many are too ill to benefit from any form of therapy other than supportive care. The remaining one-third have so-called limited disease confined to one hemithorax and the ipsilateral supraclavicular fossa [2, 31. In this latter group the tumor is usually far too extensive to be considered amenable to operation, and primary treatment consists of chemotherapy. A small proportion of patients with SCLC have extremely localized disease. This group is important because for these patients the prospects of operation and cure are good. The aim of this report is to analyze the results of surgical intervention in patients with small cell lung cancer at the Royal Brompton National Heart and Lung Hospital over a 7-year period. All operations were conducted by a single surgical team using a uniform staging protocol.
Material and Methods We undertook a retrospective review of all cases of carcinoma of the lung seen by one surgeon (P.G.) in the period 1'380 to 1987. During the period of investigation, 87 patients with the diagnosis of SCLC were referred for staging and treatment. All patients underwent careful history and clinical examination. Routine blood tests included a full blood count, liver function tests, and serum calcium determinations. In addition, each patient had a chest radiograph and bronchoscopy. Those still considered to have operable disease proceeded to computed tomographic scan of Accepted for publication Feb 24, 1992. Address re,>rint requests to Dr Shah, Department of Thoracic Surgery, Royal Brompton National Heart & Lung Hospitals, Sydney St, London SW3 6NP, England.
0 1992 by The Society of Thoracic Surgeons
Results After preoperative staging, 30 patients (34.5%) were considered to have resectable disease and 57 patients (65.5%) were considered to have inoperable disease due to mediastinal lymph gland involvement or evidence of distal metastases. The male to female ratio was 19:11 and the age range was 39 to 77 years (mean, 58 years). In 18 of these 30 patients the diagnosis of SCLC was made before operation by either bronchoscopy and biopsy or transcutaneous needle biopsy. Ten patients had the diagnosis made at the time of operation. In 2 patients the records were not clear as to whether the diagnosis was made before or at the time of the operation. The bone scans and bone marrow biopsies performed as a routine in patients with a preoperative diagnosis of SCLC were negative in all cases. At thoracotomy, 28 patients (93.3%) went on to a resection and 2 patients (6.7%), both with stage I11 disease, were found to have nonresectable disease. Of the patients who underwent resection, 14 had pneumonectomies (50.0%), 9 had lobectomies (32.1%), 3 had sleeve resections (10.7%), 1 had bilobectomy (3.3%), and 1 had wedge resection (3.3%). There were no postoperative deaths. The tumor was in a central position in 14 patients (46.7%) and peripheral in 16 patients (53.3%). According to the international TNM staging classification [4], after operation 14 patients (46.7%) had stage I disease (T1 NO MO, 8 patients; T2 NO MO, 6 patients), 5 patients (16.7%) had stage I1 disease (TI N1 MO, 1 patient; T2 N1 MO, 4 0003-4975/92/$5.00
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
Ann Thorac Surg 1992;54:49%501
499
Fig 1. Actual 5-year survival after operation for ' small cell lung cancer.
% Survival
--R
-Stage
1
+Stage
2
+Stage
3
+-Overall
Survival
patients), and 11 patients (36.7%)had stage I11 disease (T3 NO MO, 8 patients; T3 N1 MO, 1 patient; T3 N2 MO, 2 patients). Although many of the patients were treated in conjunction with our oncological colleagues, none of the patients received adjuvant therapy. The survival data in our patients are shown in Figure 1. The actual overall 5-year survival in the patients who underwent thoracotomy was 43.3%. Actual survival with respect to the stage of the disease showed that the 5-year survival for stage I was 57.1% and stage I11 was 55.5%. No patients with stage I1 disease survived 5 years. Survival with respect to the node status of the patients is shown in Figure 2. There were 22 patients and 6 patients with NO and N1 disease, respectively. The 2 patients who were found to have inoperable disease both had evidence of N2 disease at operation. The actual 5-year survival for patients with NO disease was 59.1%. No patients with N1 disease survived 5 years. The 5-year survival was 42.8% in patients with a centrally located tumor compared with 50.0% in those with a peripherally located tumor.
Comment Small cell lung cancer is a highly malignant tumor with particular cellular and histopathological characteristics.
The clinical features include a rapid growth rate with a short doubling time [5], a propensity for early metastases via lymphatic and hematological spread, and dramatic response to chemotherapy, with a very short survival time in patients who are not subjected to any treatment. Without any therapy the median survival in one group of patients was 2.8 months after diagnosis [6]. By 1970, operation in SCLC had been abandoned as primary treatment due to the overall poor prognosis-5-year survival rates ranging from 2.5% to 21.4% [7-lo]. In an attempt to clarify the matter, the Medical Research Council of Great Britain [ l l ] carried out a prospective comparative trial in which patients with SCLC were subjected to either surgical resection (71 patients) or radiation therapy (73 patients). Of the surgical group only l patient, who went on to refuse operation, survived 5 years. With the advent of effective cytotoxic agents, it became clear that SCLC was sensitive to chemotherapy, and this became the mainstay of therapy. Several studies reported rates of complete remission as high as 70% to 90% of the cases in patients with limited disease. Although combination chemotherapy produced encouraging figures in terms of remission, few patients achieved long-term survival. In patients with limited disease the median survival rate was 14 months compared with 9 months for those
% Survival
Fig 2. Actual 5-year survival versus node status after operation for small cell lung cancer.
-
40
30 -
20 10
~
0
1
-NO Disease
2
3
4 4
Years +N1
Disease
+-
Overall Survival
5
500
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
patients with more extensive disease [12-141. In a longitudinal study reporting the results in 3,681 patients with SCLC, Souhami and Law [15] found that current treatment resulted in a 2-year survival of 8.5% and 2.2% for those with limited and extensive disease, respectively, and an overall 2-year survival of 5.9%. Chemotherapy was effective in eradicating the occult disease but not the primary tumor. Recurrences were often within the thorax [16, 171. Irradiation was used either concurrently or as an adjunct to chemotherapy to overcome this problem. The results were disappointing, most trials concluding that radiotherapy did not result in any substantial decrease in the incidence of recurrence [1&23]. In 19:’5, the Armed Forces Asymptomatic Pulmonary Nodule Study published results showing that the 5-year survival of patients after resection of nodules containing SCLC was the same as that of other cell types [24]. Subsequently, results from other studies suggested that the total rejection of operation as a treatment option may have been premature [25]. These findings, coupled with the failuire of chemotherapy and radiotherapy in markedly improving prognosis, revived interest in the role of surgical resection in the management of SCLC. Clearly, accurate preoperative staging is especially important in SCLC if one is to avoid unnecessary operations. In our group 93.3% of the patients with SCLC selected for operation went on to have a resection performed, which is a figure that is comparable to our experience with nonsmall cell carcinoma of the lung [26]. Furthermore, it is now generally agreed that patients who have T4/N2-3 disease are not suitable for operative management. It is therefore very important that patients have meldiastinoscopy or mediastinotomy before thoracotomy, in addition to other routine preoperative investigations [27]. This contrasts with our strategy in patients with nor\-small cell lung cancer, in whom we have adopted a selective approach to mediastinoscopy based on the findings of a computed tomographic scan of the thorax. We have not assumed this to apply in SCLC, and mediastinal exploration is routinely performed if the diagnosis is, known preoperatively [28]. Routine bone marrow examination, however, in this series did not reveal any evidence of metastatic disease. This would suggest that this investigation need no longer be a part of preoperative staging [29]. Many authors consider the TNM staging system irrelevant in the classification of small cell lung cancer and restrict staging categories to two g r o u p s t h o s e with limited disease (tumor that is confined to one hemithorax, sometimes including ipsilateral nodes, but restricted to one radiation field) and those with extensive disease (all patients beyond these boundaries) [25]. In our series, we found that with precise preoperative and postoperative staging the TNM classification provided useful information about survival. In 1985, Davis and associates [30] surveyed all longterm survivors of small cell carcinoma within a specified population. This study stated that once the stage of the disease was taken into account, the only factor relating to
Ann Thorac Surg 1992;54:49%501
survival beyond 2 years was whether the patient received operation as the first line of treatment. Furthermore, within a particular stage, those patients who did not receive operation were subject to a fourfold increase in the risk of death compared with those who did. Prasad and co-workers [31] argue that many patients are denied operation because there are physicians who consider small cell lung cancer as a nonsurgical disease. Recently the role of operation has been reconsidered in combination with adjuvant therapy. Preliminary results reported by Karrer and co-workers [32, 331 state that for stage I and 11, operation should be followed by chemotherapy and radiotherapy, whereas for stage I11 disease debulking chemotherapy should be given and adjuvant operation should be considered in those patients who respond. Unfortunately these studies do not have a control arm, and our study demonstrates that equally good results can be achieved with operation alone in a carefully selected group of patients. In our series the actual overall 5-year survival for patients with small cell carcinoma who underwent resection was 43.3%, which compares favorably with other series in which patients received adjuvant therapy in addition to operation [25, 341. It is important for all who treat this usually fatal condition to remain alert for the rare patient who may benefit from operation. In the case of these fortunate few patients the prospects of surgical cure are similar to those for non-small cell carcinoma of the lung [35]. We thank Ms Sally Jordan for her help in the preparation of the manuscript.
References 1. Katlic M, Carter D. Prognostic implications of histology, size and location of primary tumors. Prog Cancer Ther 1979;ll: 143-50. 2. Crompton G. Small cell lung cancer [Editorial]. Br Med J 1990;300:209-10. 3. Mountain CF. Operation for small cell carcinoma revisited [Editorial]. J Clin Oncol 1987;5:687-8. 4. Mountain CF. A new international staging system for lung cancer. Chest 1986;89:225=3S. 5. Chahinian P. Relation between tumor doubling time and anatomoclinical features in 50 measurable pulmonary cancers. Chest 1972;61:340-5. 6. Maassen W, Greschuchna D. Small cell carcinoma of the lung-to operate or not? Surgical experience and results. Thorac Cardiovasc Surg 1986;34:71-6. 7. Siddons AH. Cell type in the choice of cases of carcinoma of the bronchus for surgery. Thorax 1962;17308-9. 8. Taylor AB, Shinton NK, Waterhouse JA. Histology of bronchial carcinoma in relation to prognosis. Thorax 1963;18: 178-81. 9. Goldman KP. Histology of lung cancer in relation to prognosis. Thorax 1965;20:298-302. 10. Lennox SC, Flavell G, Pollock DJ, et al. Results of resection for oat-cell carcinoma of the lung. Lancet 1968;2:925-7. 11. Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus. Tenyear follow-up. Lancet 1973;2:63-5. 12. Johnson DH, Greco FA. Small cell carcinoma of the lung. CRC Crit Rev Oncol Hematol 1986;4:303-36.
SHAHETAL OPERATION FOR SMALL CELL LUNG CANCER
Ann Thorac Surg 1992;54:49%501
13. Hande KR, Des Prez RM. Current perspectives in small cell lung cancer. Chest 1984;85:669-77. 14. Aisner J, Albert0 P, Bitran J, et al. Role of chemotherapy in small cell cancer: a consensus report of the international association for the Study of Lung Cancer workshop. Cancer Treat Rep 1983;673743. 15. Souhami RL, Law K. Longevity in small cell lung cancer. A report to the Lung Cancer Subcommittee of the United Kingdom Coordinating Committee for Cancer Research. Br J Cancer 1990;61:584-9. 16. Greco FA, Johnson DH, Hainsworth JD, et al. Chemotherapy of small cell lung cancer. Semin Oncol 1985;11:31-7. 17. Spiro SG. Chemotherapy for small cell lung cancer [Editorial]. Br Med J (Clin Res) 1985;290:413-4. 18. Lichter AS, Bunn PA Jr, Ihde DC, et al. The role of radiation therapy in the treatment of small cell lung cancer. Cancer 1985;55:2163-75. 19. Perez CA, Einhom L, Oldham RK, et al. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol 1984;2: 120c-8. 20. Johnson RE, Brereton HD, Kent CH. "Total" therapy for small cell carcinoma of the lung. Ann Thorac Surg 1978;25: 51&5. 21. Souhami RL, Geddes DM, Spiro SG, et al. Radiotherapy in small cell cancer of the lung treated with combination chemotherapy: a controlled trial. Br Med J (Clin Res) 1984;288: 16434. 22. Byhardt RS, Cox JD, Libnoch JA, Komaki R, Holoye PY, Anderson T. Multiagent chemotherapy, prophylactic neuroaxis irradiation and consolidative irradiation for small cell carcinoma of the lung. Ann J Clin Oncol 1985;8:504-11. 23. Mira JG, Livingston RB, Moore TN, Chen T, Batley F. Influence of chest irradiation in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study. Cancer 1982;50:126&72. 24. Higgins GA, Shields TW, Keehan RJ. The solitary pulmonary
25. 26. 27. 28. 29. 30. 31. 32. 33.
34.
35.
501
nodule. Ten-year follow-up of Veterans Administrationarmed forces cooperative study. Arch Surg 1975;110:570-5. Shields TW, Higgins GA Jr, Matthews MJ, Keehn RJ. Surgical resection in the management of small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1982;84:481-8. Gaer JA, Goldstraw P. Intraoperative assessment of nodal staging at thoracotomy for carcinoma of the bronchus. Eur J Cardiothorac Surg 1990;4:207-10. Sridhar KS, Hussein AM, Thurer RJ. Evolving role of surgical treatment in limited-disease small cell lung carcinoma. J Surg Oncol 1989;40:155-61. Goldstraw P, Kurzer M, Edwards D. Pre-operative staging of lung cancer: accuracy of computed tomography versus mediastinoscopy. Thorax 1983;38:10-5. Campling B, Quirt I, DeBoer G, Feld R, Shepherd FA, Evans WK. Is bone marrow examination in small-cell lung cancer really necessary? Ann Intern Med 1986;105:508-12. Davis S, Wright PW, Schulman SF, Scholes D, Thorning D, Hammer S. Long-term survival in small cell carcinoma of the lung: a population experience. J Clin Oncol 1985;3:80-91. Prasad US, Naylor AR, Walker WS, Lamb D, Cameron EW, Walbaum PR. Long term survival after pulmonary resection for small cell carcinoma of the lung. Thorax 1989;44:784-7. Karrer K. Rationale for surgery as the first step in the multimodality treatment of small cell lung cancer (SCLC). J Chemother 1989;1:147-50. Karrer K, Shields TW, Denck H, Hrabar 8, Vogt-Moykopf I, Salzer GM. The importance of surgical and multimodality treatment for small cell bronchial carcinoma. J Thorac Cardiovasc Surg 1989;97168-76. Shepherd FA, Ginsberg RJ, Evans WK, et al. Reduction in local recurrence and improved survival in surgically treated patients with small cell lung cancer. J Thorac Cardiovasc Surg 1983;86:498-506. Deneffe G, Lacquet LM, Verbeken E, Vermaut G. Surgical treatment of bronchogenic carcinoma: a retrospective study of 720 thoracotomies. Ann Thorac Surg 1988;45:38&3.
