III Department of Tuberculosis and Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
Received 16 July 2001; revised 22 January 2002; accepted 20 February 2002
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Abstract |
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The community-based cancer registry was set up and results were analysed to assess differences in clinicopathological parameters between women and men.
Patients and methods:
The Pulmonary Outpatient Departments supplied data on 20 561 lung cancer patients diagnosed in Poland from 1995 to 1998. Data regarding demographics, smoking, histology, treatment and survival were obtained.
Results:
There were 2875 women and 17 686 men with lung cancer. Women were younger than men (60.02 versus 62.18 years; P <0.001). Age <50 years was more frequent in women than in men (23.3% versus 12%; P <0.001). Women with small-cell lung cancer (SCLC) and adenocarcinoma were significantly younger than women with squamous cancer (58.2 and 58.2 versus 61 years; P = 0.05). Also, men with adenocarcinoma and SCLC were younger than men with squamous cancer (60.6 and 60.2 versus 62.3 years; P = 0.05). Squamous cancer was the predominant type of lung cancer both in women (32.5%) and men (55.2%). However, SCLC (26.6% versus 19.9%: P <0.001) and adenocarcinoma (21.6% versus 9.6%; P <0.001) were more frequent in women than in men. Women were more frequently non-smokers than men (18.8% versus 2.4%; P <0.001). Adenocarcinoma patients smoked less intensively than patients with squamous and SCLC both in women (31.4 versus 35.8 and 33.7 packs/year; P <0.02) and in men (38.2 versus 42 and 41.9 packs/year; P <0.002). In multivariate analysis, bad performance status, advanced stage, non-surgical treatment, age >50 years at diagnosis and male gender were significant independent negative prognostic factors.
Conclusions:
Lung cancer was six times more frequent in men than in women. Women with lung cancer were younger than men and smoked less intensively. Over-representation of adenocarcinoma and SCLC was observed in the women. Women with lung cancer had a better prognosis than men.
Key words: histology, lung cancer, prognostic factors, sex, survival
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Introduction |
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Many factors may influence the differences in lung cancer incidence between men and women. They may be connected with cigarette smoking, passive smoking, diet, occupation, indoor exposure and also with host factors that can protect against or facilitate the development of the cancer [46]. Several authors have also reported a more favourable prognosis of lung cancer in women than in men; this has been shown in population- and clinical-based studies [714]. However, there are no data in which elements of both forms of studies, i.e. large, un-selected population and clinical information, were included.
This paper focuses on the demographic factors (gender, age, smoking) and factors connected with disease (histology, performance status, stage, treatment and survival) in lung cancer patients.
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Materials and methods |
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On the basis of standardised registration card, data regarding demographics, smoking, histological type of cancer, performance status according to Eastern Cooperative Oncology Group (ECOG) scale, clinical stage of the disease, treatment and survival were available. Follow-up information was recorded every 6 months. The diagnosis of lung cancer was based on positive histological or cytological examination (according to WHO criteria), or, in some patients, on clinical and radiological appearances [15]. Patients with mixed tumours, unclassified forms and large-cell lung cancer (2654 cases) were analysed in the group of the other types. Patients without histological confirmation were excluded from analyses of clinical stage, performance status, treatment and multivariate analysis of prognostic factors.
Radiological assessment was performed in all patients, and in 16 657 (81%) patients bronchoscopy was carried out. For diagnosis, transcutaneous needle biopsy of tumour was carried out in 2519 cases (12.25%), lymph nodes biopsy in 1093 patients (5.3%), biopsy of metastases in 351 cases (1.7%) and diagnostic thoracotomy in 1973 cases (9.6%). Extent of the disease was defined according to TNM (tumournodemetastasis) criteria. Initial treatment was defined as an anticancer therapy received within 6 months of diagnosis. Survival was defined as the time between date of diagnosis and date of death or last visit. Dates of death were confirmed with the Central Address Bureau.
The comparisons of age groups as to frequency of gender, smoking, tumour histology, performance status and type of treatment were tested using the 2 method and Pearsons test. Smoking (mean values of packs/years) and age (mean values) were analysed by one-way analysis of variance. KaplanMeyer survival curves were used to present and analyse the survival data, and statistical differences were assessed by the log-rank test. Univariate and multivariate analysis by Coxs proportional hazards ratio model were used to test the significance of prognostic factors including gender, age, stage, performance status and histology, and relative risks were estimated [16].
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Results |
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Clinical stage of the disease
Data regarding clinical stage of cancer were available for 15 212 patients (91%) with histological diagnosis. Stage I cancer was recorded in a similar proportion in men as in women (27.1%). Distant metastases were observed in 1893 cases (14.8%). A significantly higher percentage of women than men with disseminated diseases was observed (20.3% versus 13.9%; P <0.001). However, the opposite situation was noticed for men and women with stage II (12.2% versus 15.2%; P = 0.03) and III (40.5% versus 43.9%; P = 0.03) disease, where a higher percentage of men than women was observed (Table 2).
Initial therapy
The NTLDRI registry includes information on treatment received within 6 months after the initial diagnosis. However, these data were not comprehensive for all therapy that patients received during the course of the disease. Sufficient data considering therapy was obtained for 12 378 patients (74%) with histological diagnosis. Significantly more women than men were treated with surgery (23.2% versus 18.8%; P <0.0001); also, a higher percentage of women were treated by surgery in combination with chemotherapy and radiotherapy (7.3% versus 5.5%; P <0.003).
Chemotherapy was administered to 29.9% of women and 28.2% of men, and radiotherapy to 14.5% of women and 14.6% of men. Over-representation of men in the groups treated symptomatically (27.9% versus 22%; P <0.0001) and refusing therapy (5% versus 3.1%; P = 0.0005) was observed (Table 5).
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Discussion |
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Age is the major determinant of cancer risk. The peak of incidence was noted in the cohort of patients aged 6069 years. In our population, the highest percentage of patients was in this group. Nevertheless, the median age of Polish patients is lower than that reported in other countries [13, 17]. Women were younger than men. This was observed for women and men when histological type was taken into account. In particular, adenocarcinoma was diagnosed in younger age both in women and in men. This relationship has been reported previously [10, 14, 17, 18].
Women were found to be more likely to have adenocarcinoma and SCLC than men. Squamous cancer was the predominant type of lung cancer among men, and <10% of them had adenocarcinoma. Different patterns of histological types of lung cancer were observed in Poland in comparison with the USA, China or Denmark, where over-representation of adenocarcinoma has been noted [17, 19, 20]. The distribution of main histological types of lung cancer in Poland was similar to that described in Finland and Scotland [2, 21, 22].
Smoking is associated with all types of lung cancer, with a doseresponse relationship. The majority of men and women in our review had a history of smoking, but significantly more women than men were non-smokers (24.5% versus 3.6%), particularly those with adenocarcinoma. The connection between smoking and lung cancer was most evident among patients with squamous and SCLC, and weaker for adenocarcinoma. There are some studies indicating that duration of smoking is more important influence on histological type of cancer than number of cigarettes smoked [5, 23]. Both men and women with squamous cancer in our study smoked more intensively than patients with other histological types of cancer. Ferguson et al. [10] and McDuffie et al. [18] obtained similar results.
Women developed lung cancer at a younger age, were more likely to be lifetime non-smokers, consumed fewer cigarettes per day and smoked for a short period of time. All those factors suggested that women are more susceptible to carcinogenic compounds of cigarette smoke and environmental noxious conditions due to genetic background [4, 2426]. Recently, it was shown that gene for gastrin-releasing peptide receptor (GRPR) was located on chromosome X [27]. The activation of this receptor has been associated with proliferative response of bronchial cells. It has been suggested that GRPR gene was expressed more frequently in women than in men in the absence of smoking, and that expression of this gene was activated earlier in women in response to tobacco smoke. Another explanation of this phenomenon may be connected with hormonal status. Estrogen replacement therapy, as well as short menstrual cycle and late menopause, have been reported to increase the risk for adenocarcinoma in women [28]. The majority of women diagnosed with lung cancer are postmenopausal; however, in this study adenocarcinoma patients were younger than patients with other histological types of lung cancer. The role of estrogen receptors in development and proliferation of lung cancer cells is not known, and conflicting results have been presented. Sex hormones influence the development of fetal lung, but lung is not a target organ for sex hormones during adulthood [28, 29]. The potential role of sex hormones in the development of lung cancer is obscure, and more data are needed to establish it.
The most important prognostic factors for lung cancer patients were performance status, clinical stage of the disease and surgical treatment. The significant role of these factors has been underlined in many clinical- and population-based studies, and also in the data presented here [14, 30].
In our material, females with lung cancer had a survival benefit compared with males, taking into account age, histology, performance status, extension of the disease and treatment. This overall survival advantage of women was described first in data based on Danish Register information, and recently by Ramalingam et al. [14] from a population-based study, and also by others [17, 3134]. Ederer and Merheimer [8], Minami et al. [31], Mark et al. [35], and Inoue et al. [36] found female gender to be a good prognostic factor for patients treated by surgery. However, Bingal and Martin [37], and Kirsh et al. [38] reported opposite results. Also, in our previous data on a smaller population of patients, female gender was found to be an independent significant positive prognostic factor [13].
Further studies are needed to elucidate all problems connected with sex-associated differences in clinico-pathological characteristics and survival of lung cancer patients.
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Acknowledgements |
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Footnotes |
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References |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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2. Charloux A, Rossignal M, Purohit A et al. International differences in epidemiology of lung carcinoma. Lung Cancer 1997; 16: 133143.[ISI][Medline]
3. Bingall JR, Martin M. Survival experience of women with bronchial carcinoma. Lancet 1972; 2: 6062.[Medline]
4. Koo LC, Ho JH-C. World wide epidemiological patterns of lung cancer in non-smokers. Int J Epidemiol 1990; 19 (Suppl 1): S14S23.[Abstract]
5. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: Examination of the evidence. J Natl Cancer Inst 1996; 88: 183190.
6. Taioli E, Wynder EL. Endocrine factors and adenocarcinoma of the lung in women. J Natl Cancer Inst 1994; 86: 869870.[ISI][Medline]
7. de Perrot M, Licker M, Bouchardy Ch et al. Sex differences in presentation, management and prognosis of patients with non-small-cell lung carcinoma. J Thorac Cardiovasc Surg 2000; 119: 2126.
8. Ederer F, Merheimer L. Sex differences in the survival of lung cancer patients. Cancer 1961; 15: 425432.[ISI]
9. Engeland A, Bjorge T, Haldorsen T, Tretli S. Prognosis of patients with lung cancer diagnosed in Norway 195493. Cancer Causes Control 1998; 9: 5765.[ISI][Medline]
10. Ferguson MK, Skosey C, Hoffman PC, Golomb HM. Sex associated differences in presentation and survival in patients with lung cancer. J Clin Oncol 1990; 8: 14021407.[Abstract]
11. Ferguson MK, Wang J, Hoffman PC et al. Sex-associated differences in survival of patients undergoing resection for lung cancer. Ann Thorac Surg 2000; 69: 245250.[ISI][Medline]
12. Johnson BE, Steinberg SM, Phelps R et al. Female patients with small-cell lung cancer live longer than male patients. Am J Med 1988; 85: 194196.[ISI][Medline]
13. Radzikowska E, Gßaz P. Female gender as a prognostic factor in lung cancer patients. Pneumonol Alerg Pol 2000; 910: 425433.
14. Ramalingam S, Pawlish K, Gadgeel S et al. Lung cancer in young patients: analysis of a surveillance, epidemiology, and end results database. J Clin Oncol 1998; 16: 651657.[Abstract]
15. World Health Organization. Histological typing of lung cancer tumours. In International classification of tumors, No. 1, 2nd edition. Geneva: World Health Organization 1981.
16. Cox DR. Regression models and life tables (with discussion). J R Stat Soc Series B 1972; 34: 187220.[ISI]
17. Olsen JH. Epidemiology of lung cancer. Eur Respir Mon 1995; 1: 117.
18. McDuffie HH, Klaassen DJ, Dosman JA. Femalemale differences in patients with primary lung cancer. Cancer 1987; 59: 18251830.[ISI][Medline]
19. Travis WD, Lubin J, Ries L, Devesa S. United States lung carcinoma incidence trends. Declining for most histologic types among men, increase among females. Cancer 1996; 77: 24642467.[ISI][Medline]
20. Seow A, Duffy SW, Ng TP et al. Lung cancer among Chinese females in Singapore 19681992: time trends, dialect group differences and implications for aetiology. Int J Epidemiol 1998; 27: 167172.[Abstract]
21. Makitaro R, Paakko P, Huhti E et al. An epidemiological study of lung cancer: history and histological types in general population in northern Finland. Eur Respir J 1999; 13: 436440.
22. Bouchardy CH, Floretta G, de Perott M et al. Determinants of long term survival after surgery for cancer of the lung. Cancer 1999; 86: 22292237.[ISI][Medline]
23. Brownson RC, Loy TS, Ingram E et al. Lung cancer in nonsmoking women. Histology and survival patterns. Cancer 1995; 75: 2933.[ISI][Medline]
24. Fontham ET, Correa P, Reynolds P et al. Environmental tobacco smoke and lung cancer in non-smoking women. A multicenter study. JAMA 1994; 271: 17521759.[Abstract]
25. Wang T, Zhou B, Shi J. Lung cancer in non-smoking Chinese women: a casecontrol study. Lung Cancer 1996; 14 (Suppl 1): S93S95.[ISI][Medline]
26. Wu AH, Yu MC, Thomas DC et al. Personal and family history of lung disease as a risk factors for adenocarcinoma of the lung. Cancer Res 1988; 48: 7279.[Abstract]
27. Shriver SP, Bourdeau HA, Gubish CT et al. Sex-specific expression of gastrin realising peptide receptor: relationship to smoking history and risk of cancer. J Natl Cancer Inst 2000; 92: 2433.
28. Taioli E, Wynder EL. Endocrine factors and adenocarcinoma of the lung in women. J Natl Cancer Inst 1994; 86: 869870.[ISI][Medline]
29. Lee YT. Better prognosis of many cancers in female: a phenomenon not explained by study of steroid receptors. J Surg Oncol 1984; 25: 255262.[ISI][Medline]
30. Mould RF, Williams RJ. Survival of histologically proven carcinoma of the lung registered in North West Thames Region 19751979. Br J Cancer 1982; 46: 9991003.[ISI][Medline]
31. Minami H, Yoshimura M, Miyamoto Y et al. Lung cancer in women. Sex associated differences in survival of patients undergoing resection for lung cancer. Chest 2000; 118: 16031609.
32. Ouellette D, Desbiens G, Emond C, Beauchamp G. Lung cancer in women compared with men: stage, treatment, survival. Ann Thorac Surg 1998; 66: 11401144.
33. Paesmands M, Sculier JP, Libert P et al. Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analysis including recursive partitioning and amalgamation algorithms in 1052 patients. J Clin Oncol 1995; 13: 12211230.[Abstract]
34. Yip D, Harper PG. Predictive and prognostic factors in small cell lung cancer: current status. Lung Cancer 2000; 28: 173185.[ISI][Medline]
35. Mark KF, Consuelo S, Philip CH. Sex-associated differences in presentation and survival in patients with lung cancer. J Clin Oncol 1990; 8: 14021407.[Abstract]
36. Inoue K, Sato M, Fujimura S et al. Prognostic assessment of 1310 patients with non-small cell lung cancer who underwent complete resection from 1980 to 1993. J Thorac Cardiovasc Surg 1998; 116: 407411.
37. Bingal JR, Martin M. Survival experience of women with bronchial carcinoma. Lancet 1972; 2: 6062.[Medline]
38. Kirsh MM, Tashian J, Sloan H. Carcinoma of the lung in women. Ann Thorac Surg 1982; 34: 3439.[Abstract]