Carcinoma of the Lung in Marvin M. Kirsh, M.D., Jeanne Tashian, M.A., and Herbert Sloan, M.D. ABSTRACT The 5-year survival of 293 men and of 78 women undergoing pulmonary resection and mediastinal lymph node dissection is compared. These patients were broken into two age groups: Group 1,40 through 49 years of age, and Group 2,50 years of age and older. They were subdivided further according to clinical stage, cell type, and sex. Of the 25 men in Group 1, 15 (60%) survived 5 years, while 98 (37%) of the 268 men in Group 2 survived 5 years. Among the 31 women in Group 1, 5 (16%) survived for 5 years, while 15 (32%) of the 47 women in Group 2 survived for that length of time. The survival among women in the younger age group was significantly lower than for both groups of women in the older age group ( p = 0.0335) and men in the younger age group (p = 0.0033). This is believed to be due to the higher incidence of both Stage I11 disease and adenocarcinoma in the younger women. Twenty-two of the younger women (71 /o) were classified Stage I11 compared with 14 (30%) of the older women. Fourteen younger men (56%) had reached Stage 111, and 101 older men (38%) were classified as Stage 111. These data suggest that sex is an important factor in determining survival because there appears to be a relationship between it and the stage of the disease, and cell type. Overall, women had a poorer 5-year survival than men. Younger women have a strikingly lower survival than any other group, which is explained by their higher incidence of both Stage 111 classification and adenocarcinoma. During the past 60 years, there has been a steady increase in the incidence of carcinoma of the lung. The American Cancer Society estimated that 122,000 new cases of lung cancer would be detected in 1981 and that 105,000 From the Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI. Presented at the Twenty-eighth Annual Meeting of the Southern Thoracic Surgical Association, Palm Beach, FL, NOV 5-7, 1981. Address reprint requests to Dr. Kirsh, C7079 University Hospital, Ann Arbor, MI 48109. people would perish from the disease in that year [l]. Thirty years ago the male to female incidence of lung cancer was about 5 : 1, but with the increase in smoking among women that began during World War 11, this ratio has been decreasing in recent years. Of the 122,000 new cases predicted for 1981, 88,000 were in men and 34,000 in women, a ratio of 2.6: 1. Between 1950 and 1975, the percentage of increase in lung cancers in women was 238.8% and in men, 184.8%. The present study was undertaken to compare the 5-year survival of men and women undergoing resection for bronchogenic carcinoma and to ascertain what factors, if any, influenced survival. Material and Methods Over an 11-year period at the University of Michigan Medical Center, 371 people survived a curative resection for bronchogenic carcinoma; 78 of the survivors were women and 293 were men. Anterior mediastinal exploration or mediastinoscopy was not performed preoperatively in any of these patients, and none of them had roentgenographic evidence of mediastinal or subcarinal lymph node involvement. Whether lobectomy or pneumonectomy was carried out depended on the location and extent of the carcinoma. The perihilar and hilar lymph nodes were removed en bloc with the primary lesion whenever possible. Following resection, the superior mediastinal, subaortic, subcarinal, and paraesophageal lymph nodes were removed completely. The resection was considered curative if all the gross tumor was excised, even if the operation included resection of the adjacent diaphragm, pericardium, or chest wall. Postoperative mediastinal irradiation was given to those patients who had undergone curative resection and, in addition, had mediastinal metastases. The total dose administered was 5,000 to 6,000 rads given in daily doses of 200 rads over a five- to six-week period. 34 0003-49751821070034-06$01.25 @ 1982 by The Society of Thoracic Surgeons
35 Kirsh, Tashian, and Sloan: Carcinoma of the Lung in Since there was not a large number of patients with acanthoadenocarcinoma, oat cell carcinoma, undifferentiated carcinoma, or large cell carcinoma, only the results of treatment in patients with squamous cell carcinoma or adenocarcinoma were analyzed. Retrospectively, the patients were classified according to the guidelines established by the American Joint Committee on Cancer Staging and End Results Reporting [2]. In an attempt to ascertain the effect of age on survival, the patients were arbitrarily divided into two groups. Group 1 patients were younger than 50 years of age whereas Group 2 patients were 50 years of age or older. The generalized Cochran-Mantel-Haenzel test was used to compare survival between the two age groups of women and for a preliminary statistical analysis of adjusted and unadjusted survival figures for both men and women. In a subset analysis of Group 2 for both men and women, a check for interaction between the factors was done by using a weighted least squares model containing all main effects and all two-way interaction terms [3]. Results The majority of the women (47 of 78) had adenocarcinoma (Table 1). Only 20 of the 78 women survived 5 years free from disease (Table 2). Survival according to stage of disease and histological cell type is shown in Tables 3, 4, 5, and 6. The most striking finding was that the 5-year survival for the younger women was only 16% whereas it was 32% for the patients 50 years old or older ( p = 0.0335). Twenty-two of the 31 younger women had Stage I11 disease whereas only 14 of the older women were classified as Stage I11 (see Table 5). In addition, 22 of the 31 younger women (71%) had adenocarcinoma, while only 25 (53%) of the 47 older women did (see Table 6). The majority of the men had squamous cell carcinoma regardless of age distribution (see Table 1). Of the 293 patients, 113 lived 5 years free from disease (see Table 2). Survival according to histological cell type and stage of disease are listed in Tables 3, 4, 5, and 6. The 5-year survival for the younger age group was 66%, and it was 37% for the patients older than 50 years. There was no difference between the two groups with respect to histological cell type or stage of disease (see Tables 3-6). Comment Since the 1930s, the incidence of bronchogenic carcinoma has increased steadily. In men there was a rapidly rising incidence until 1960, but a slower rise thereafter. On the other hand, the rise in incidence of bronchogenic carcinoma in women was slow until 1960, but since then it has become rapid. In some series, the rate of increase in lung cancer in women exceeds the rate of increase in men [41. A study by the Connecticut Cancer Registry in 1977 revealed some startling figures [5]. Among persons aged 35 to 44 years, between 1970 and 1974, the male to female incidence was a little less than 2: 1. In 1975, there were more lung cancers among women than among men in this age group. The ratio was 0.9:l. A study from the New York State Department of Health predicted that if current trends continue, lung cancer will surpass breast cancer as the leading cause of cancer deaths in women by 1984 [6]. Annegers and colleagues [7] reviewed the incidence of bronchogenic carcinoma in a rural community in Minnesota over a 40-year period. They found that the incidence of lung cancer increased in men in every decade except the last. During that decade, the increase continued only in men age 65 and more; in men age 25 to 64 years, the rate plateaued. Among women, no change of rate was found in the period 1935 through 1964; the first increase occurred in the decade 1965 to 1974. The explanation for the recent more rapid rise of lung cancer in women compared with men is uncertain. In men squamous cell, oat cell, and large cell undifferentiated carcinoma have a strong association with smoking, while the association with adenocarcinoma is much less strong. It is believed by some that the cause of the growing incidence of carcinoma of the lung in women is the increased number of smoking women [4]. If this is true, then there should be an increase in the proportion of histological cell
~ ~~~ 36 The Annals of Thoracic Surgery Vol34 No 1 July 1982 Table 1. Occurrence of Histological Cell Type according to Sex and Age Cell Type 40-49 50-75 40-49 50-75 Squamous cell 16 (64) 167 (62) 6 (19) 13 (28) Adenocarcinoma 4 (16) 72 (27) 22 (71) 25 (53) Other 5 (20) 29 (11) 3 (10) 9 (19) Total 25 268 31 47 anumbers in parentheses are percentages. Table 2. Five-Year Survival according to Histological Cell Type and Sex CelI Type Patients Survivors Patients Survivors Squamous cell 183 78 (42.6) 19 6 (31.6) Adenocarcinoma 76 22 (28.9) 47 9 (19.1) Other 34 13 (38.2) 12 5 (41.7) Overall 293 113 (38.6) 78 20 (25.6) Numbers in parentheses are percentages. Table 3. Five-Year Survival according to Stage and Sex Stage Patients Survivors Patients Survivors I 130 70 (53.8) 31 16 (51.6) I1 48 15 (31) 11 0 (0) I11 115 28 (24.8) 36 4 (11.1) anumbers in parentheses are percentages. types in bronchogenic carcinoma in which smoking has been incriminated, namely, squamous cell, oat cell, and undifferentiated carcinoma. However, an increase in these histological cell types found in lung cancer has not occurred in women in either Europe or the United States. Beamis and associates [4] reviewed the histological cell types of women with bronchogenic carcinoma from 1957 through 1972. They found no change in the histological cell distribution during the period of study. The most frequently encountered tumor was adenocarcinoma. A similar prepon- derance of adenocarcinoma in women has been reported by others. Similarly, Kennedy [8] in a review from 1955 through 1971 of 168 women with lung cancer could find no evidence of changing histological patterns. Wynder and co-workers [9, 101 have shown that cigarette smoking is closely associated with squamous cell and oat cell carcinoma. In our opinion, the influence of smoking on the increased incidence of lung cancer in women is not clear. Perhaps, as some investigators believe, there are inherent differences in the airways of the lung in men and women and a differential response