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Bronchogenic Carcinoma: A Study of Patients Treated at Capital Hospital, Peking, China
Bronchonenic Carcinoma: A Study-of Patients Treated at Capital Hospital, Peking, China Le-Tian Xu, M.D., Cheng-Fu Sun, M.D., Ze-Jian Li, M.D., and Liang-Hong Wu, M.D.
ABSTRACT From 1961 to 1972, 123 patients with lung cancer underwent operations at Capital Hospital, Peking, China. Ninety-six patients had resectable lesions and 27 did not, a resectability rate of 78%. Four patients (4.2%) died immediately postoperatively. Complications occurred in 8 (8.3%) patients. Five-year survival in this group of 92 survivors was 26 (28.3%). Ten-year survival among 49 patients was 10 (20.470). Among the 92 five-year survivors, 41.2'/0 had squamous cell carcinoma, 25% had adenocarcinoma, and 16% had undifferentiated carcinoma. Patients with squamous cell carcinoma had a much longer survival than the others. Six factors appear to influence survival after resection: cell type, presence of lymph node metastases, presence of tumor emboli in blood vessels, sex, age, and location. Men about 50 years of age, with a peripherally located squamous cell tumor and with no tumor emboli or lymph node metastases, have a good chance of surviving a pulmonary resection for ten years.
From 1961to 1972,123 patients with lung cancer were treated surgically at Capital Hospital, Peking, China. This hospital, formerly known as Peking Union Medical College Hospital, was built and established as a teaching hospital in the Peking Union Medical College in 1921. The medical college and hospital service were interrupted by World War I1 and were reestablished in the late 1940s. The hospital was taken over by the Chinese government in 1951 and incorporated in the Chinese Academy of Medical Sciences in 1957. The hospital is responsible for From the Department of Surgery, Capital Hospital, Chinese Academy of Medical Sciences, Peking, China. Accepted for publication Sept 24, 1981. Address reprint requests to Dr. Xu, Vice-head and Associate Professor, Department of Surgery, Capital Hospital, Peking, China.
605
the health of approximately 100,000 people who live in the neighborhood surrounding it, but it also receives referrals from all of Peking, a city of 6 million people, and from other parts of China.
Material During the eleven-year period from 1961 to 1972, 123 patients with cancer of the lung underwent operation. The majority of these patients had already been evaluated at an outlying hospital. The criteria for the choice of patients for operation were similar to those widely accepted in the United States [l-61. Ninety-six of the patients had resectable lesions and 27 patients did not. Twenty-nine pneumonectomies and 67 lobectomies were performed, for a resectability rate of 78 YO. Results Four patients died in the immediate postoperative period, 2 of respiratory obstruction and 2 of hemorrhage, for an operative mortality of 4.2%. Postoperative complications occurred in 8.3YO of the patients and included 6 patients with empyema, 1with a bronchopleural fistula, and 1 with a hemothorax. The five-year survival in this group of 92 patients was 28.3%. Forty-nine patients were followed for ten years, and 20.4% of them survived. Eighty percent of the patients were men. The patients ranged from 29 to 68 years old; 30% of them were less than 40 years old. Among the 92 patients who survived pulmonary resection, 41.2% had squamous cell carcinoma, 25% had adenocarcinoma, and 16% had undifferentiated carcinoma. There was one alveolar cell carcinoma. Survival at both five and ten years showed marked differences according to cell type. Those patients with squamous cell carcinoma had a much higher
0003-4975/82/060605-04$01.25 @ 1982 by The Society'of Thoracic Surgeons
606
The Annals of Thoracic Surgery Vol 33 No 6 June 1982
Table 1. Relationship between Histological Cell Types and Long-Term Survival Rate after Resection ~~
~
Cell Type
Five-Year Survivala
Squamous cell carcinoma Adenocarcinoma Undifferentiated cell carcinoma Alveolar cell carcinoma Total
14/34 (41.2)
7/17 (41.2)
8/32 (25) 4/25 (16)
1/14 (7.1) 2/17 (11.8)
Oil
011
26/92b (28.3)
Ten-Year Survivala
10149 (20.4)
"Numbers in parentheses are percents. bIncludes 4 patients ultimately lost to follow-up.
Table 2 . Relationship between Hilar Lymph Node Metastasis and Long-Term Survival after Resection Cell Type
Five-Year Survivala
Squamous cell carcinoma Without hilar metastasis With hilar metastasis Adenocarcinoma Without hilar metastasis With hilar metastasis Undifferentiated cell carcinoma Without hilar metastasis With hilar metastasis Alveolar cell carcinoma
14/34 (41.2) 10115 4/19 8/32 (25) 8/19 0113 4/25 (16) 011 4/24 Oil
7/17 (41.2) 7/15 0119 1/14 (7.1) 1/19 0113 2/17 (11.8)
26/92 (28.3)
10149 (20.4)
Total
Ten-Year Survivala
011
2/24 011
"Numbers in parentheses are percents
rate of survival than those with adenocarcinoma or undifferentiated carcinoma. Survival for patients with adenocarcinoma and undifferentiated carcinoma was similar (Table 1). Patients with metastatic lesions in the hilar lymph nodes fared differently from those without such metastatic lesions. The increased survival when lymph node metastases were not present is clearly indicated in Table 2, which relates survival to the presence or absence of hilar metastases. During this time the presence or absence of metastatic lesions in the mediastinum was not recorded. Those patients with squamous cell lesions who had hilar metastases underwent irradiation postoperatively, 3,000 to 4,000 rads. Patients with hilar metastases due to adenocarcinoma or undifferentiated carcinoma received either radiation therapy or chemotherapy consisting of regimens of Endoxan (cyclophosphamide),
bleomycin, mitomycin C, 5-fluorouracil, and vincristine, when these adjuvants became available. The chemotherapy regimen was not extremely helpful. Seven of 25 patients with undifferentiated cell carcinoma and 2 of 32 patients with adenocarcinoma had intravascular tumor cell emboli on microscopic examination of the resected specimen. Eight of these 9 patients died of widespread metastatic lesions within a year of resection. One patient with adenocarcinoma survived for five years. Among the 10 patients surviving for more than ten years after resection of pulmonary cancer, 9 were men and 1 was a woman. They ranged from 30 to 68 years old (mean, 49 years). In 8 of the patients a lobectomy was performed and in 2 patients, a pneumonectomy. Seven patients had squamous cell carcinoma, and 3 had either adenocarcinoma or undifferentiated carcinoma. Interestingly, lymph node metas-
607
Xu et al: Bronchogenic Carcinoma
tases were present in 2 patients with squamous cell carcinoma and in 2 patients with undifferentiated cell carcinoma.
term survival. Of the 56 patients reported by Watson [12], 46 were men, and 50 of 53 tenyear survivors reported by Kirsh and colleagues were men [l]. Comment 5. Age. The average age of the 10 patients surviving more than ten years following resecCarcinoma of the lung is one of the most frequently found malignancies in the city area of tion was 49 years. In patients younger than 49 years at the time of resection, long-term Peking and represents 13.1% of all deaths from malignancies (18.1% for men and 10.5% for survival has been poorer, apparently bewomen). Because the frequency of carcinoma cause many of the tumors in the younger age of the lung is increasing and because surgigroup were adenocarcinoma or undiffercal resection still provides the best hope of entiated carcinoma, which carry a worse cure, more patients are undergoing exploration prognosis. In patients older than 60 years, and resection for isolated pulmonary lesions, we have found a higher incidence of carwhether or not histological verification of the diopulmonary disease, which has an untumor has been accomplished preoperatively. favorable influence on long-term survival. The rate of resectability has increased to 79% in 6. Location of tumor. In 7 of the ten-year survivors, the lesion was peripheral and was recent years with an operative mortality of 1% and improving long-term survival [7, 81. more than 3.5 cm at its greatest diameter. In this group of patients, the five-year surviAppearance of the tumor in the right as opval of 28.3% bore a close relationship to the tenposed to the left lung was found to have no year survival of 20.4% following resection. For statistical significance. patients with squamous cell carcinoma, the two rates were the same. There were six factors in In conclusion, long-term survival in this these 92 patients that appeared to influence group of patients appeared to be influenced survival after resection. primarily by cell type and by the presence or absence of lymph node metastases. Age, sex, 1. Cell type. Patients with squamous cell car- and existence of tumor emboli played a less imcinoma had a much greater chance of sur- portant, but still significant, role. If then a paviving for long periods following operation tient is male, around 50 years of age, with a than those with adenocarcinoma or undif- peripherally located squamous cell tumor no ferentiated carcinoma. This has been sub- larger than 3.5 cm in diameter, and without lymph node metastases, he should have a good stantiated in several reports [ l , 2, 7, 9, 101. 2. Presence of lymph node metastases. In our chance of surviving a pulmonary resection for patients this element adversely influenced ten or more years. survival, particularly in those patients with adenocarcinoma or undifferentiated carci- We thank Dr. Herbert Sloan for his helpful advice and encouragement in the preparation of this paper. noma. Some authors believe the presence of lymph node metastases outweighs the in- References 1. Kirsh MM, Rotman H, Argenta L, et al; Carfluence of cell type [3, 5, 111. cinoma of the lung: results of treatment over ten 3. Presence of tumor emboli in blood vessels. years. Ann Thorac Surg 21:371, 1976 This occurrence had an especially grave 2. Bennett DE, Ferguson TB: Adenocarcinoma of prognosis. the lung in men: clinical-pathological study of 4. Sex. Nine of 10 patients who survived ten 100 cases. Cancer 23:431, 1969 3. Higgins GA, Lawton R, Heilbrunn A, Keehn RJ: years or more were men. Eighty percent of Prognostic factors in lung cancer: surgical asthe patients undergoing resection were men, pects. Ann Thorac Surg 7:472, 1969 and the number of patients with squamous 4. Paulson DL, Reish JS: Long-term survival after cell carcinoma surviving ten or more years resection for bronchogenic carcinoma. Ann Surg was greater among men. Our findings con184:324, 1976 firm those of other groups reporting long5. Slack NH, Chamberlain A, Bross IDJ: Predicting
608 The Annals of Thoracic Surgery
6.
7. 8. 9.
Vol 33 No 6 June 1982
survival following surgery for bronchogenic carcinoma. Chest 62:433, 1972 Stanford W, Spivey CG, Larsen GL, et al: Results of treatment of primary carcinoma of the lung: analysis of 3000 cases. J Thorac Cardiovasc Surg 72:441, 1976 Wu YK: Thoracic Surgery. Peking, Publisher of People’s Health, 1974, pp 380-403 Huang CS: Textbook of Surgery. Peking, Publisher of People’s Health, 1979, pp 179-186 Collier FC, Enterline HT, Kyle RH, et al: The prognostic implications of vascular invasion in primary carcinoma of the lung: clinico-
pathologic correlation of 225 cases with 100°/o follow-up. Arch Pathol 66:594, 1958 10. Rienhoff WF 111, Talbert JL, Wood S Jr: Bronchogenic carcinoma: a study of cases treated at Johns Hopkins Hospital from 1933 to 1958. Ann Surg 161:674, 1965 11. Shields Tw, Yee J, Conn JH, Robinette CD: Relationship of cell type and lymph node metastasis to survival after resection of bronchogenic carcinoma. Ann Thorac Surg 20:501, 1975 12. Watson WL: Lung Cancer: A Study of Five Thousand Memorial Hospital Cases. St. Louis, Mosby, 1968, pp 511-526
ABSTRACT From 1961 to 1972, 123 patients with lung cancer underwent operations at Capital Hospital, Peking, China. Ninety-six patients had resectable lesions and 27 did not, a resectability rate of 78%. Four patients (4.2%) died immediately postoperatively. Complications occurred in 8 (8.3%) patients. Five-year survival in this group of 92 survivors was 26 (28.3%). Ten-year survival among 49 patients was 10 (20.470). Among the 92 five-year survivors, 41.2'/0 had squamous cell carcinoma, 25% had adenocarcinoma, and 16% had undifferentiated carcinoma. Patients with squamous cell carcinoma had a much longer survival than the others. Six factors appear to influence survival after resection: cell type, presence of lymph node metastases, presence of tumor emboli in blood vessels, sex, age, and location. Men about 50 years of age, with a peripherally located squamous cell tumor and with no tumor emboli or lymph node metastases, have a good chance of surviving a pulmonary resection for ten years.
From 1961to 1972,123 patients with lung cancer were treated surgically at Capital Hospital, Peking, China. This hospital, formerly known as Peking Union Medical College Hospital, was built and established as a teaching hospital in the Peking Union Medical College in 1921. The medical college and hospital service were interrupted by World War I1 and were reestablished in the late 1940s. The hospital was taken over by the Chinese government in 1951 and incorporated in the Chinese Academy of Medical Sciences in 1957. The hospital is responsible for From the Department of Surgery, Capital Hospital, Chinese Academy of Medical Sciences, Peking, China. Accepted for publication Sept 24, 1981. Address reprint requests to Dr. Xu, Vice-head and Associate Professor, Department of Surgery, Capital Hospital, Peking, China.
605
the health of approximately 100,000 people who live in the neighborhood surrounding it, but it also receives referrals from all of Peking, a city of 6 million people, and from other parts of China.
Material During the eleven-year period from 1961 to 1972, 123 patients with cancer of the lung underwent operation. The majority of these patients had already been evaluated at an outlying hospital. The criteria for the choice of patients for operation were similar to those widely accepted in the United States [l-61. Ninety-six of the patients had resectable lesions and 27 patients did not. Twenty-nine pneumonectomies and 67 lobectomies were performed, for a resectability rate of 78 YO. Results Four patients died in the immediate postoperative period, 2 of respiratory obstruction and 2 of hemorrhage, for an operative mortality of 4.2%. Postoperative complications occurred in 8.3YO of the patients and included 6 patients with empyema, 1with a bronchopleural fistula, and 1 with a hemothorax. The five-year survival in this group of 92 patients was 28.3%. Forty-nine patients were followed for ten years, and 20.4% of them survived. Eighty percent of the patients were men. The patients ranged from 29 to 68 years old; 30% of them were less than 40 years old. Among the 92 patients who survived pulmonary resection, 41.2% had squamous cell carcinoma, 25% had adenocarcinoma, and 16% had undifferentiated carcinoma. There was one alveolar cell carcinoma. Survival at both five and ten years showed marked differences according to cell type. Those patients with squamous cell carcinoma had a much higher
0003-4975/82/060605-04$01.25 @ 1982 by The Society'of Thoracic Surgeons
606
The Annals of Thoracic Surgery Vol 33 No 6 June 1982
Table 1. Relationship between Histological Cell Types and Long-Term Survival Rate after Resection ~~
~
Cell Type
Five-Year Survivala
Squamous cell carcinoma Adenocarcinoma Undifferentiated cell carcinoma Alveolar cell carcinoma Total
14/34 (41.2)
7/17 (41.2)
8/32 (25) 4/25 (16)
1/14 (7.1) 2/17 (11.8)
Oil
011
26/92b (28.3)
Ten-Year Survivala
10149 (20.4)
"Numbers in parentheses are percents. bIncludes 4 patients ultimately lost to follow-up.
Table 2 . Relationship between Hilar Lymph Node Metastasis and Long-Term Survival after Resection Cell Type
Five-Year Survivala
Squamous cell carcinoma Without hilar metastasis With hilar metastasis Adenocarcinoma Without hilar metastasis With hilar metastasis Undifferentiated cell carcinoma Without hilar metastasis With hilar metastasis Alveolar cell carcinoma
14/34 (41.2) 10115 4/19 8/32 (25) 8/19 0113 4/25 (16) 011 4/24 Oil
7/17 (41.2) 7/15 0119 1/14 (7.1) 1/19 0113 2/17 (11.8)
26/92 (28.3)
10149 (20.4)
Total
Ten-Year Survivala
011
2/24 011
"Numbers in parentheses are percents
rate of survival than those with adenocarcinoma or undifferentiated carcinoma. Survival for patients with adenocarcinoma and undifferentiated carcinoma was similar (Table 1). Patients with metastatic lesions in the hilar lymph nodes fared differently from those without such metastatic lesions. The increased survival when lymph node metastases were not present is clearly indicated in Table 2, which relates survival to the presence or absence of hilar metastases. During this time the presence or absence of metastatic lesions in the mediastinum was not recorded. Those patients with squamous cell lesions who had hilar metastases underwent irradiation postoperatively, 3,000 to 4,000 rads. Patients with hilar metastases due to adenocarcinoma or undifferentiated carcinoma received either radiation therapy or chemotherapy consisting of regimens of Endoxan (cyclophosphamide),
bleomycin, mitomycin C, 5-fluorouracil, and vincristine, when these adjuvants became available. The chemotherapy regimen was not extremely helpful. Seven of 25 patients with undifferentiated cell carcinoma and 2 of 32 patients with adenocarcinoma had intravascular tumor cell emboli on microscopic examination of the resected specimen. Eight of these 9 patients died of widespread metastatic lesions within a year of resection. One patient with adenocarcinoma survived for five years. Among the 10 patients surviving for more than ten years after resection of pulmonary cancer, 9 were men and 1 was a woman. They ranged from 30 to 68 years old (mean, 49 years). In 8 of the patients a lobectomy was performed and in 2 patients, a pneumonectomy. Seven patients had squamous cell carcinoma, and 3 had either adenocarcinoma or undifferentiated carcinoma. Interestingly, lymph node metas-
607
Xu et al: Bronchogenic Carcinoma
tases were present in 2 patients with squamous cell carcinoma and in 2 patients with undifferentiated cell carcinoma.
term survival. Of the 56 patients reported by Watson [12], 46 were men, and 50 of 53 tenyear survivors reported by Kirsh and colleagues were men [l]. Comment 5. Age. The average age of the 10 patients surviving more than ten years following resecCarcinoma of the lung is one of the most frequently found malignancies in the city area of tion was 49 years. In patients younger than 49 years at the time of resection, long-term Peking and represents 13.1% of all deaths from malignancies (18.1% for men and 10.5% for survival has been poorer, apparently bewomen). Because the frequency of carcinoma cause many of the tumors in the younger age of the lung is increasing and because surgigroup were adenocarcinoma or undiffercal resection still provides the best hope of entiated carcinoma, which carry a worse cure, more patients are undergoing exploration prognosis. In patients older than 60 years, and resection for isolated pulmonary lesions, we have found a higher incidence of carwhether or not histological verification of the diopulmonary disease, which has an untumor has been accomplished preoperatively. favorable influence on long-term survival. The rate of resectability has increased to 79% in 6. Location of tumor. In 7 of the ten-year survivors, the lesion was peripheral and was recent years with an operative mortality of 1% and improving long-term survival [7, 81. more than 3.5 cm at its greatest diameter. In this group of patients, the five-year surviAppearance of the tumor in the right as opval of 28.3% bore a close relationship to the tenposed to the left lung was found to have no year survival of 20.4% following resection. For statistical significance. patients with squamous cell carcinoma, the two rates were the same. There were six factors in In conclusion, long-term survival in this these 92 patients that appeared to influence group of patients appeared to be influenced survival after resection. primarily by cell type and by the presence or absence of lymph node metastases. Age, sex, 1. Cell type. Patients with squamous cell car- and existence of tumor emboli played a less imcinoma had a much greater chance of sur- portant, but still significant, role. If then a paviving for long periods following operation tient is male, around 50 years of age, with a than those with adenocarcinoma or undif- peripherally located squamous cell tumor no ferentiated carcinoma. This has been sub- larger than 3.5 cm in diameter, and without lymph node metastases, he should have a good stantiated in several reports [ l , 2, 7, 9, 101. 2. Presence of lymph node metastases. In our chance of surviving a pulmonary resection for patients this element adversely influenced ten or more years. survival, particularly in those patients with adenocarcinoma or undifferentiated carci- We thank Dr. Herbert Sloan for his helpful advice and encouragement in the preparation of this paper. noma. Some authors believe the presence of lymph node metastases outweighs the in- References 1. Kirsh MM, Rotman H, Argenta L, et al; Carfluence of cell type [3, 5, 111. cinoma of the lung: results of treatment over ten 3. Presence of tumor emboli in blood vessels. years. Ann Thorac Surg 21:371, 1976 This occurrence had an especially grave 2. Bennett DE, Ferguson TB: Adenocarcinoma of prognosis. the lung in men: clinical-pathological study of 4. Sex. Nine of 10 patients who survived ten 100 cases. Cancer 23:431, 1969 3. Higgins GA, Lawton R, Heilbrunn A, Keehn RJ: years or more were men. Eighty percent of Prognostic factors in lung cancer: surgical asthe patients undergoing resection were men, pects. Ann Thorac Surg 7:472, 1969 and the number of patients with squamous 4. Paulson DL, Reish JS: Long-term survival after cell carcinoma surviving ten or more years resection for bronchogenic carcinoma. Ann Surg was greater among men. Our findings con184:324, 1976 firm those of other groups reporting long5. Slack NH, Chamberlain A, Bross IDJ: Predicting
608 The Annals of Thoracic Surgery
6.
7. 8. 9.
Vol 33 No 6 June 1982
survival following surgery for bronchogenic carcinoma. Chest 62:433, 1972 Stanford W, Spivey CG, Larsen GL, et al: Results of treatment of primary carcinoma of the lung: analysis of 3000 cases. J Thorac Cardiovasc Surg 72:441, 1976 Wu YK: Thoracic Surgery. Peking, Publisher of People’s Health, 1974, pp 380-403 Huang CS: Textbook of Surgery. Peking, Publisher of People’s Health, 1979, pp 179-186 Collier FC, Enterline HT, Kyle RH, et al: The prognostic implications of vascular invasion in primary carcinoma of the lung: clinico-
pathologic correlation of 225 cases with 100°/o follow-up. Arch Pathol 66:594, 1958 10. Rienhoff WF 111, Talbert JL, Wood S Jr: Bronchogenic carcinoma: a study of cases treated at Johns Hopkins Hospital from 1933 to 1958. Ann Surg 161:674, 1965 11. Shields Tw, Yee J, Conn JH, Robinette CD: Relationship of cell type and lymph node metastasis to survival after resection of bronchogenic carcinoma. Ann Thorac Surg 20:501, 1975 12. Watson WL: Lung Cancer: A Study of Five Thousand Memorial Hospital Cases. St. Louis, Mosby, 1968, pp 511-526