SEARCH

SEARCH BY CITATION

Keywords:

  • lung carcinoma;
  • age;
  • gender;
  • survival;
  • prognosis

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

The results from previous studies suggested that the clinical characteristics and outcomes of patients with lung carcinoma vary between gender and age groups. The objective of the current study was to assess the trend in the evolution of the histologic types in Taiwan and to compare the outcomes of patients with lung carcinoma between different gender and age groups.

METHODS

Patients with primary lung carcinoma were identified through the cancer registry system. Clinical records were reviewed and analyzed for age, gender, disease stage, histology, treatment modalities, and survival. A multivariate analysis using a Cox proportional hazards model was applied for gender, age (by decade), histologic type, disease stage, and treatment modality.

RESULTS

Between 1991–1999, 2714 patients with histologically or cytologically proven lung carcinoma were included. Adenocarcinoma was the major cell type of lung carcinoma (52.5%), with a significant trend toward an increase in adenocarcinoma during the study period. A significantly high percentage of adenocarcinoma was demonstrated in female patients (73.5%), who also had better survival compared with male patients (P = 0.002), especially in the group age 50–69 years. Patients age < 40 years also had a poor prognosis, which was worse compared with the prognosis for patients age 40–59 years. patients who had adenocarcinoma had a better survival rate compared with patients who had other histologic types (relative risk, 0.78; 95% confidence interval, 0.69–0.87).

CONCLUSIONS

Adenocarcinoma was predominant in female patients and emerged as a greater problem than other histologic types in Taiwan, potentially raising the importance of studies regarding the benefit of population diversity in new antitumor therapies, such as gefitinib. Female patients with lung carcinoma had a better prognosis than male patients in the group age 50–69 years, warranting further studies on potential prognostic factors associated with middle age, such as hormone status. Cancer 2005. © 2005 American Cancer Society.

Lung carcinoma is the leading cause of cancer mortality in most countries, including Taiwan.1–3 The rate of increase in lung carcinoma mortality in Taiwan is the highest in the world.4, 5 Approximately 80% of tumors are classified histologically as nonsmall cell lung carcinoma, and the 5-year survival rate is only 14%.6–8 The clinical characteristics of patients with lung carcinoma may vary among different groups with respect to gender and age. For gender differences, previous studies suggest that female gender was a favorable prognostic factor for nonsmall cell lung carcinoma in a surgical series of patients.9–11 However, the lung carcinoma mortality in females in the United States is rising continuously.8

For age differences, various investigations have concluded inferior or equivalent survival for young patients compared with older patients, but the results are controversial. Several oncologists believe that the characteristic features in younger patients with lung carcinoma differ from those in elderly patients in light of a high incidence of female patients,12–17 a high incidence of adenocarcinoma as the histologic type,7, 12–19 and a high incidence of biologic tumor aggressiveness.12, 13, 16, 19 Moreover, the difference in the prognosis for younger and older patients remains controversial.12, 15–17, 19–22 Possible explanations for the conflicting results include the small number of patients enrolled in the study, restriction to surgically treated patients, differences in disease stage at the time of presentation, and genetic, racial, or environmental differences in the populations studied.

The importance of gender and age differences in patients with lung carcinoma needs to be elucidated fully because of its implication in the design of experimental protocols for targeted chemoprevention, early disease screening, molecular marker-based staging, and individualized treatment. The current study was designed to characterize patients with lung carcinoma in different age groups and between genders with regard to the distribution of histologic types, clinical stages, treatments, and survival.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patients with a diagnosis of lung carcinoma who were admitted to the National Taiwan University Hospital (NTUH) between January 1991 and December 1999 were identified from a computer registration data base using the International Classification for Diseases, Ninth Revision coding system. The diagnosis of lung carcinoma was based on histologic examination of biopsy specimens or on fine-needle aspiration cytology. Exclusion criteria included the diagnosis of other types of malignancies established before lung carcinoma and a clinical diagnosis without biopsy or aspiration of lung tumor.

The clinical records of patients who were included in the study were reviewed for age at diagnosis, gender, family history of malignancy, history of smoking, disease stage, histology, treatment modalities, and survival. The disease stage was determined by a combination of surgical and pathologic findings according to the current TNM classification system for lung carcinoma23 if the patient underwent lung tumor resection. For patients who did not undergo surgical intervention, clinical staging was performed according the patients' computed tomography (CT) scan of the thorax, including the upper part of abdomen, and radionuclide scanning of the bone. A brain CT scan was not mandatory unless neurologic symptoms were present. Stage IIIB and IV lung carcinoma were defined as unresectable. Histologic analysis of the tumor was based on the World Health Organization classification system for cell types.24 The patients were divided into 6 age groups as follows: ages < 40 years, 40–49 years, 50–59 years, 60–69 years, 70–79 years, and ≥ 80 years.

Patient characteristics were compared using the chi-square test, and the mean age at diagnosis for males and females was examined by the Student t test. All reported P values are two-sided. Comparisons between patients in terms of gender, age, tumor histology, disease stage, and type of treatment were tested using chi-square analysis and the Pearson test. The same analyses were performed among different age groups. Survival was defined as the time between the date of diagnosis and the date of death or last visit. Survival functions were analyzed by the Kaplan–Meier method, and log-rank tests were performed to compare the difference in survival between patients with lung carcinoma according to gender and age group. A Cox proportional hazards model was used to calculate the hazard ratio and its 95% confidence interval (95% CI) for gender, age group, cell type, disease stage (resectable and unresectable), and treatment. A P value ≤ 0.05 was considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Clinical Characteristics

Between January 1991 and December 1999, 3018 patients with a diagnosis of lung carcinoma were identified from the computer registration data base. Of these, 2714 patients with histologically or cytologically proven lung carcinoma were included in the current study. The mean patient age was 63.4 years (range, 15–96 years), and 898 patients (33.1%) were female. Among the different age groups, there were 104 patients (3.8%) age < 40 years, 253 patients (9.3%) ages 40–49 years, 531 patients (19.6%) ages 50–59 years, 920 patients (33.9%) ages 60–69 years, 765 patients (28.2%) ages 70–79 years, and 141 patients (5.2%) age ≥ 80 years.

There were 223 patients (8.1%) with small cell lung carcinoma and 2491 patients with nonsmall cell lung carcinoma, including 1425 patients with adenocarcinoma (52.5%), 890 patients with squamous cell carcinoma (32.8%), 148 patients with undifferentiated carcinoma (5.5%), and 28 patients with large cell carcinoma (1%). Among the patients studied, 2168 patients had complete data for disease stage. Among the patients with small cell lung carcinoma, 173 patients had records for disease stage, including 100 patients (57.8%) with extensive-stage disease and 73 patients (42.2%) with limited-stage disease. Among the patients with nonsmall cell carcinoma, 301 patients had Stage I disease (15.0%), 152 patients had Stage II disease (7.6%), 796 patients had Stage III disease (39.7%), and 757 patients had Stage IV disease (37.7%).

The annual number of patients with lung carcinoma at NTUH had a trend toward an increase from 1991 to 1999 (1991, n = 223 patients; 1992, n = 241 patients; 1993, n = 244 patients; 1994, n = 270 patients; 1995, n = 279 patients; 1996, n = 343 patients; 1997, n = 325 patients; 1998, n = 370 patients; 1999, n = 419 patients). The male-to-female (M/F) ratio was constant at 2:1 during the study period. The trend toward an increase was demonstrated in all age groups except those age < 40 years (numbers for 1991 and 1999, respectively; age < 40 years, 13 patients and 19 patients; ages 40–49 years, 22 patients and 33 patients; ages 50–59 years, 46 patients and 80 patients; ages 60–69 years, 85 patients and 123 patients; ages 70–79 years, 47 patients and 134 patients; age ≥ 80 years, 10 patients and 30 patients). The trend toward an increase in the number of patients with lung carcinoma was due mainly to the annual increase in the number of patients with adenocarcinoma (Fig. 1).

thumbnail image

Figure 1. The annual number of patients with lung carcinoma according to different histologic types at the National Taiwan University Hospital. The trend toward an increase in the number of patients was due mainly to the annual increase in patients with adenocarcinoma. SCLC: small cell lung carcinoma, SCC: squamous cell carcinoma.

Download figure to PowerPoint

Gender Differences

For patients with lung carcinoma, there were some gender differences. The mean age at diagnosis for males was older compared with females (age 64.8 years vs. 60.5 years, respectively; P < 0.001). Adenocarcinoma was the most common type of lung carcinoma in both genders, but females (n = 660 patients; 73.5%) had a significantly higher percentage of adenocarcinoma compared with males (n = 765 patients; 42.1%; P < 0.001). Males had a higher proportion of squamous cell carcinoma (n = 742 patients; 40.9%) than females (n = 148 patients; 16.5%; P < 0.001). In addition, males (n = 185 patients; 10.2%) were more likely to have small cell lung carcinoma than females (n = 38 patients; 4.2%; P < 0.001). There was no statistical difference noted between the proportion of patients with large cell carcinoma and the proportion of patients with undifferentiated carcinoma (Table 1). For patients with small cell lung carcinoma, there was no difference between the genders in terms of the distribution by disease stage. For patients with nonsmall cell lung carcinoma who had a complete staging work-up, females had a higher rate of Stage I disease (18.5% vs. 13.1%; P = 0.001) and a lower rate of Stage III disease (35.0% vs. 42.2%; P = 0.002) (Table 2). There were 479 male patients (26.4%) and 263 female patients (29.3%) who received conservative treatments. The difference was not significant (Table 3).

Table 1. Distribution by Histology and Gender in Patients with Lung Carcinoma
HistologyNo. of patients (%)P value
Male (n = 1816)Female (n = 898)
Adenocarcinoma765 (42.1)660 (73.5)<0.001
Squamous cell carcinoma742 (40.9)148 (16.5)<0.001
Large cell carcinoma23 (1.3)5 (0.6)0.085
Undifferentiated carcinoma101 (5.6)47 (5.2)0.723
Small cell lung carcinoma185 (10.2)38 (4.2)<0.001
Table 2. Distribution by Disease Stage and Gender in Patients with Lung Carcinoma
Disease stageNo. of patients (%)P value
Male (n = 1304)Female (n = 702)
  1. NSCLC: nonsmall cell lung carcinoma, SCLC: small cell lung carcinoma.

NSCLC   
 Stage I171 (13.1)130 (18.5)0.001
 Stage II107 (8.2)45 (6.4)0.147
 Stage III550 (42.2)246 (35.0)0.002
 Stage IV476 (36.5)281 (40.0)0.120
SCLC   
 Limited stage57 (40.7)16 (48.5)0.416
 Extensive stage83 (59.3)17 (51.5) 
Table 3. Distribution by Treatment Modality and Gender in Patients with Lung Carcinoma
Treatment modalityNo. of patients (%)
Male (n = 1816)Female (n = 898)
Surgery496 (27.3)300 (33.4)
Chemotherapy650 (35.8)281 (31.3)
Radiotherapy699 (38.5)314 (35.0)
Conservative treatment479 (26.4)263 (29.3)

The median survival of female patients with lung carcinoma was significantly longer (12 months) compared with their male counterparts (10 months), indicating a better survival in females (Fig. 2). With respect to histology, the difference in survival between genders was significant among the patients with lung adenocarcinoma. The median survival of female patients with lung adenocarcinoma was significantly longer compared with their male counterparts with lung adenocarcinoma (male vs. female: 11 months vs. 14 months, respectively; P = 0.002) and with large cell carcinoma (male vs. female: 5 months vs. 35 months, respectively; P = 0.024). However, the differences were not significant in patients with other histologic types of lung carcinoma. Survival also was better for females with advanced lung carcinoma compared with their males counterparts (Stage III, P = 0.012; Stage IV, P = 0.094). After adjusting for treatment, the difference became more evident (Stage III, P = 0.005; Stage IV, P = 0.039).

thumbnail image

Figure 2. Survival analysis for males (n = 1816 patients; dotted line) and females (n = 898 patients; solid line) with lung carcinoma. The divergence between the curves representing the male and female groups is evident, with a significantly shorter survival observed among male patients (P < 0.001; log-rank test).

Download figure to PowerPoint

Age Differences

The M/F ratio was 0.93 for patients age < 40 years and 0.83 for patients ages 40–49 years. However, the M/F ratio increased with increasing patient age (ages 50–59 years, 1.87; ages 60–69 years, 2.30; ages 70–79 years, 2.77; and age ≥ 80 years, 2.61). With regard to distribution according histologic type among the different age groups, we noted a linear trend toward a decrease in adenocarcinoma and a trend toward an increase in squamous cell carcinoma as patient age increased (Table 4). The proportion of patients with adenocarcinoma was highest in the group age < 40 years, whereas the proportion of patients with squamous cell carcinoma was highest in the group age ≥ 80 years. The proportion of patients with small cell lung carcinoma was lowest in the group age < 40 years and was highest in the groups age > 59 years (Table 4).

Table 4. Distribution by Histology and Age Group in Patients with Lung Carcinoma
HistologyAge group: No. of patients (%)
< 40 yrs (n = 104)40–49 yrs (n = 253)50–59 yrs (n = 531)60–69 yrs (n = 920)70–79 yrs (n = 765)≥ 80 yrs (n = 141)
Adenocarcinoma81 (77.9)171 (67.6)317 (59.7)458 (49.8)334 (43.7)64 (45.4)
Squamous cell carcinoma16 (15.4)49 (19.4)145 (27.3)320 (34.8)301 (39.3)59 (41.8)
Small cell3 (2.9)15 (5.9)34 (6.4)86 (9.3)72 (9.4)13 (9.2)
Large cell1 (1.0)2 (0.8)6 (1.1)10 (1.1)8 (1.0)1 (0.7)
Undifferentiated carcinoma3 (2.9)16 (6.3)29 (5.5)46 (5.0)50 (6.5)4 (2.8)

Patients in the groups age < 40 years (68.1%) and > 80 years (70.4%) were more likely to have advanced-stage disease (Stage IIIB and IV) at the time of initial presentation than patients in the other age groups (ages 40–49 years, 65.0%; ages 50–59 years, 65.1%; ages 60–69 years, 59.3%; and ages 70–79 years, 64.9%) (Table 5). Despite a high proportion of patients with advanced-stage disease, most patients age < 40 years underwent surgery, received chemotherapy, or received radiotherapy (71.2%), whereas patients age ≥ 80 years underwent conservative treatment only (64.6%) (Table 6).

Table 5. Distribution by Disease Stage and Age Group in Patients with Lung Carcinoma
Disease stageAge group: No. of patients (%)
< 40 yrs (n = 72)40–49 yrs (n = 183)50–59 yrs (n = 403)60–69 yrs (n = 669)70–79 yrs (n = 574)≥ 80 yrs (n = 105)
  1. NSCLC: nonsmall cell lung carcinoma, SCLC: small cell lung carcinoma.

NSCLC      
 Stage I8 (11.1)26 (14.2)73 (18.1)116 (17.3)70 (12.2)8 (7.6)
 Stage II6 (8.3)15 (8.2) 27 (6.7)58 (8.7)42 (7.3)4 (3.8)
 Stage III28 (38.9)73 (39.9)136 (33.7)254 (38.0)252 (43.9)53 (50.5)
 Stage IV30 (41.7)69 (37.7)167 (41.4)241 (36.0)210 (36.6)40 (38.1)
SCLC      
 Limited stage1 (100.0)6 (42.9)9 (39.1)33 (51.6)20 (33.9)4 (33.3)
 Extensive stage0 (0.0)8 (57.1)14 (60.9)31 (48.4)39 (66.1)8 (66.7)
Table 6. Distribution by Treatment Modality and Age Group in Patients with Lung Carcinoma
Treatment modalityAge group: No. of patients (%)
< 40 yrs (n = 104)40–49 yrs (n = 253)50–59 yrs (n = 531)60–69 yrs (n = 920)70–79 yrs (n = 765)≥ 80 yrs (n = 141)
Surgery26 (25)95 (37.5)163 (30.6)312 (33.9)191 (24.9)10 (7.1)
Chemotherapy52 (50)115 (45.5)232 (43.6)322 (35.0)194 (25.3)17 (12.1)
Radiotherapy31 (29.8)102 (40.3)217 (40.8)361 (39.2)262 (34.2)42 (29.8)
Conservative treatment30 (28.8)47 (16.8)102 (19.2)208 (22.6)271 (35.4)84 (59.6)

For patients with lung carcinoma, there seemed to be a trend toward decreased survival as age increased, except for patients in the group age < 40 years. The median survival of patients in the different age groups were as follows: age < 40 years, 11 months; ages 40–49 years, 15 months; ages 50–59 years, 12 months; ages 60–69 years, 11 months; ages 70–79 years, 9 months; and age ≥ 80 years, 7 months. Patients in the group ages 40–49 years had the longest median survival (15 months), whereas the median survival of patients age < 40 years was similar to that for the group ages 60–69 years (11 months). Similar trends in survival were demonstrated in both genders. Female patients had significantly better survival than male patients in the groups ages 50–59 years (females vs. males: 14 months vs. 10 months; P = 0.017) and ages 60–69 years (females vs. males: 14 months vs. 10 months; P = 0.003). No significant gender difference in median survival was found among patients in the other age groups. After adjustment by histologic distribution, the survival of female patients with adenocarcinoma was significantly better compared with the survival of male patients in the group ages 50–59 years (females vs. males: 16 months vs. 12 months; P = 0.042), whereas male patients with squamous cell carcinoma had better survival compared with the survival of female patients in the group ages 70–79 years (males vs. females: 10 months vs. 5 months; P = 0.019). For patients with undifferentiated lung carcinoma, female patients had better survival at ages 40–49 years (P = 0.003) and worse survival at ages 70–79 years (P = 0.049). However, the numbers of patients may have been too small for generalization.

Outcomes and Prognostic Factors

Multivariate analysis using a Cox forward regression model was conducted for gender, age group, histology, disease stage, and treatment modality. Patients with male gender (relative risk [RR], 1.13; 95% CI, 1.01–1.27), unresectable disease stage (Stages IIIB and IV: RR, 3.21; 95% CI, 2.83–3.64), and conservative treatments (RR, 1.95; 95% CI, 1.72–2.22) had a poor survival. Patients with adenocarcinoma had a better survival compared with patients who had other cell types (RR, 0.78; 95% CI, 0.69–0.87).

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

This study demonstrated the trend evolution of the distribution in histologic cell types and stages of patients with lung carcinoma in Taiwan with respect to gender and different age groups. It has been shown that adenocarcinoma is a predominant lung carcinoma cell type in female patients, and adenocarcinoma has become more of an emerging problem than the other cell types of lung carcinoma. In addition, female patients with lung carcinoma had a better survival than males. Patients with lung adenocarcinoma had a better prognosis than patients with all other cell types.

From 1991 to 1999, there was a trend toward an increase in the annual number of patients with lung carcinoma at NTUH that was due mainly to the annual increase in patients with adenocarcinoma. During this period, the proportion of female patients with lung adenocarcinoma remained high (range, 61.9–77.8%), although the proportion of male patients was increasing (from 33.8% to 46.4%). A study from the Roswell Park Cancer Institute (Buffalo, NY) in the 1970s reported a trend toward an increase in adenocarcinoma for both genders, but especially in women.25 This study was followed by reports that confirmed those results by Stanley and by Lanzotti et al.26, 27 A multivariate analysis by O'Connell et al. in 1986 further elucidated these trends.28 In a recent study in the U.S. based on the Surveillance, Epidemiology, and End Results (SEER) Program data base, the rate of adenocarcinoma rose among African-American and white females, declined in 1987 for African-American males, and reached a plateau in 1991 for white males.29 In another large-scale study in Denmark, adenocarcinoma was the most frequent histologic subtype among women and was the only subtype that increased in incidence among men.30

These results suggest an the emerging trend toward an increase in lung adenocarcinoma, especially for females, among the subtypes of lung carcinoma. The possible reasons for the increasing incidence of adenocarcinoma have been studied. A study by Thun et al. demonstrated that the increase in lung adenocarcinoma since 1950 was more consistent with a change in smoking behavior and cigarette design than with diagnostic advances.31 However, there has been no significant change in the percentage of smoking in male patients with lung carcinoma, suggesting that other factors may account for the increasing lung adenocarcinoma in males. Changes in cigarette manufacturing with low-tar and low-nicotine products, likewise, may increase the risk of peripheral lung tumors, such as adenocarcinoma.31, 32

Our data showed a significantly high proportion of female patients with lung adenocarcinoma (73.5%), which was higher than the data presented in Western countries. Xie et al. presented a ratio of female adenocarcinoma of 33% in Canada.33 In the study of Lienert et al., female adenocarcinomas comprised 29% of all lung carcinomas in Germany.34 In the population-based studies of patients with lung carcinoma in Sweden35 and Denmark,30 the percentages of female lung adenocarcinoma were 31.8% and 39.1%, respectively. Similar reports of an increasing trend in female lung adenocarcinomas were noted in several studies in Asia. A study of lung carcinoma in the annual pathologic autopsies in Japan showed a relatively high percentage of female patients with lung adenocarcinoma (58%) from 1958 to 1997, with an increase (62%) during the period from 1988–1997.36 A hospital-based study in Korea also showed a significantly high percentage of female patients with adenocarcinoma (45%) from 1981–1990, with an increasing trend for adenocarcinoma.37 The difference in the proportion of female patients with lung adenocarcinoma between populations in Western countries and Asian countries raises the importance of ethnic differences in the incidence of lung adenocarcinoma.

Recently, gefitinib, which is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, showed antitumor activity in patients with previously treated, advanced nonsmall cell lung carcinoma. Two large-scale, multicenter, randomized Phase II studies38, 39 have demonstrated clinically significant antitumor activity of gefitinib monotherapy in patients with advanced nonsmall cell lung carcinoma who previously had received platinum-based chemotherapy. The clinical trials of gefitinib have revealed significant variability in the response to gefitinib, with higher responses seen in Japanese patients than in a predominantly European-derived population.38 In the U.S., partial clinical responses to gefitinib have been observed most frequently in women, in nonsmokers, and in patients with adenocarcinoma.39–41 In more recent studies describing the EGFR gene mutation that was associated with the response of gefitinib, EGFR gene mutation also was more common in women, nonsmokers, and patients with adenocarcinoma.42–44 In the current study, we demonstrated the relative high percentage of female patients with lung adenocarcinoma who mostly were nonsmokers. Coupled with the previous literature concerning a higher percentage of female patients with lung adenocarcinoma among Asian populations, we considered that gefitinib may have more treatment success in Asian patients with nonsmall cell lung carcinoma than in patients from Western countries. Together, including the striking differences in the frequency of EGFR mutation and responses to gefitinib between Japanese patients and patients from Western countries, these findings warrant further studies regarding variations in the molecular pathogenesis of carcinoma in different ethnic, cultural, and geographic groups, and the results argue for the benefit of population diversity in such clinical trials.

In the current study, the overall M/F ratio was 2.02, with a consistent M/F ratio of 2.0 annually from 1991 to 1999. The low M/F ratio was different from other reports from different countries, including 2.1 in the U.S.,8 2.24 in Denmark,30 2.40 in Germany,34 2.7–2.8 in Japan,36 and 2.8 in Sweden.35 This finding warrants a research of risk factors for the development of lung carcinoma in females. However, the M/F ratio trend toward an increase as patient age increased (ages 50–59 years, 1.87; ages 60–69 years, 2.30; ages 70–79 years, 2.77; and age ≥ 80 years, 2.61). Because the percentage of smoking increased in both genders as their age increased (males: age < 40 years, 64.4%; ages 40–49 years, 72.5%; ages 50–59 years, 74.2%; ages 60–69 years, 83.9%; ages 70–79 years, 88.3%; and age ≥ 80 years, 83.8%; females: age < 40 years, 5.7%; ages 40–49 years, 5.6%; ages 50–59 years, 8.0%; ages 60–69 years, 12.2%; ages 70–79 years, 25.1%, and age ≥ 80 years, 24.3%), and because the M/F ratio of smokers did not increase as age advanced (smoking M/F ratio: age < 40 years, 9.67; ages 40–49 years, 11.28; ages 50–59 years, 17.1; ages 60–69 years, 15.6; ages 70–79 years, 9.7; and age ≥ 80 years, 9.2), smoking may not be a major cause of the increasing M/F ratio. Other factors that may influence the gender difference among patients who develop lung carcinoma should be investigated.

The trend toward an increase in lung carcinoma during the 1991–1999 period was demonstrated in all age groups except patients age < 40 years, possibly reflecting an underestimation of younger patients with lung carcinoma. Less exposure to carcinogens also may be an important factor. For the histologic distribution in different age groups, a linear trend toward a decrease in adenocarcinoma was noted together with an increasing trend in squamous cell carcinoma as age increased. The proportion of adenocarcinoma was highest in the group of patients age < 40 years, whereas the proportion of squamous cell carcinoma was highest in the group of patients age > 80 years. The proportion of small cell lung carcinoma was lowest among patients in the group age < 40 years and highest among patients in the groups age > 59 years. The changing pattern of histologic distribution may be due to an increase in the proportion of smokers in the different age groups (age < 40 years, 32.7%; ages 40–49 years, 36.6%; ages 50–59 years, 51.3%; ages 60–69 years, 62.0%; ages 70–79 years, 71.5%; and age ≥ 80 years, 67.6%).

A significant difference in survival between genders in patients with lung adenocarcinoma and large cell carcinoma was found in the current study. However, the differences were not significant in patients with other cell types of lung carcinoma. The survival among female patients with adenocarcinoma was significantly better compared with the survival among males in the group age 50–59 years. Survival also was better for female patients with advanced lung carcinoma compared with their male counterparts. However, there was no significant difference in disease stage or treatment modality between the genders. The gender difference in survival among patients with adenocarcinoma according to age group raises the importance of studying factors that are associated with middle age, such as hormone status, which may influence the prognosis of female patients with lung carcinoma, especially adenocarcinoma.

Multivariate analyses using a Cox forward regression model were conducted for gender, age group, histology, disease stage, and treatment modality. Patients with male gender (RR, 1.13; 95% CI, 1.01–1.27), unresectable disease stage (Stage IIIB and IV) (RR, 3.21; 95% CI, 2.83–3.64), and conservative treatments (RR, 1.95; 95% CI, 1.72–2.22) had a poorer survival. Patients with adenocarcinoma had a better survival (RR, 0.78; 95% CI, 0.69–0.87), but the survival among patients in the different age groups showed no statistically significant differences. These data were similar to those reported from a recent study by the nationwide SEER registry.7 However, the results of that study demonstrated that age ≥ 50 years at diagnosis was an independent predictor of poor survival.7 An important limitation of the current analysis is that age is compound variable that encompasses a variety of other factors, which could not be controlled in the current study, such as comorbidity and performance status. The data in our study support prior studies of prognostic factors in lung carcinoma that found age was of little significance.45–47

For patients with lung carcinoma, there appears to be a trend toward decreased survival for patients age ≥ 40 years. Patients ages 40–49 years had a longest median survival. Patients age < 40 years (68.1%) and those age > 80 years (70.4%) were more likely to have advanced-stage disease (Stage IIIB and IV) at the time of initial presentation than patients ages 40–80 years (ages 40–49 years, 65.0% ages 50–59 years, 65.1%; ages 60–69 years, 59.3%; and ages 70–79 years, 64.9%). However, the difference was not significant.

Despite the high proportion of patients with advanced-stage disease in the current study, most patients age < 40 years underwent surgery, received chemotherapy, or received radiotherapy (71.2%)l whereas patients age ≥ 80 underwent conservative treatment only (64.6%). The treatments did not influence survival among patients in the different age groups. Further study is warranted to clarify the question why patients age < 40 years who have lung carcinoma do not have better survival compared with patients age ≥ 40 years with lung carcinoma. The possible explanation may be that respiratory symptoms are ignored in young age patients, which may delay the diagnosis of lung carcinoma and result in the high proportion of patients who are diagnosed in advanced stages.

There were some limitations in the current study. We performed many tests to compare variables in different categories, such as age group at diagnosis, gender, disease stage, histologic tumor type, and treatment modality. The multiplicity of these comparisons may have inflated the false-positive rate; thus, the results need to be confirmed in larger scale studies. In addition, the population analyzed primarily included patients who presented to our hospital. These patients may represent a smaller group of younger patients with earlier stage disease compared with the entire population of patients with lung carcinoma in Taiwan or with the Asian patient population overall. Further population-based studies on gender and age differences among patients with lung carcinoma will help to reinforce the conclusions of the current study.

Lung adenocarcinoma, especially among females, has become a more emergent problem than other cell types of lung carcinoma in Taiwan. The high proportion of female patients with lung adenocarcinoma may imply the importance of studies regarding the benefit of population diversity in new antitumor therapies, such as gefitinib, in Taiwan and in other Asian countries. Female patients with lung carcinoma had a better prognosis than males among the group of patients ages 50–69 years. This finding warrants further studies on the factors associated with middle age, such as hormone status, that may influence prognosis.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES