Surgically Resected Lung Cancer in Young Adults Kenji Sugio, MD, Teruyoshi Ishida, MD, Satoshi Kaneko, MD, Hideki Yokoyama, MD, and Keizo Sugimachi, MD Department of Surgery 11, Faculty of Medicine, Kyushu University, Fukuoka, Japan

Twenty-two patients, 40 years old or younger, were surgically treated for lung cancer between 1974 and 1989. The male to female ratio was 1.21. Ten patients were symptomatic, with the average duration of symptoms being 3.6 months. There were 13 patients with adenocarcinoma and 9 patients with large cell carcinoma. In terms of postoperative stages, 5 patients were classified in stage I, 10 in stage IIIa, 5 in stage IIIb, and 2 in stage IV. Complete resection was performed in 14 patients, incomplete resection in 6, and exploratory thoracotomy in 2. The 3-year survival rate after complete resection was

66.2% in young patients, which was not significantly different from the 65.2% 3-year survival rate in older patients. There was no significant difference between the young and older groups according to histological cell type and TNM staging. In cases of incomplete resection or exploratory thoracotomy, 4 of 8 patients had been alive more than 2 years after operation. These results suggest that a long-term survival in the young patients is expected to be almost the same as that in the older patients after either complete resection or incomplete resection. (Ann Thorac Surg 1992;53:127-31)

e [I, 21 reported previously that bronchogenic carcinoma occurs mainly in patients in the seventh decade of life, and there is no significant difference in long-term survival rate between the elderly group and the younger group. In contrast, lung cancer is rarely found in young patients, especially before 40 years of age. There are characteristic features in young patients with lung cancer that differ from those in older patients with lung cancer, that is, a relatively high incidence of female patients, a high incidence of adenocarcinoma, and a paucity of cases of squamous cell carcinoma [3-51. Several reports suggest a poor prognosis [6, 71, whereas others suggest that there is no significant difference in long-term survival between young patients and older patients [3,4]. However, a detailed analysis has not yet been performed on young patients who have undergone surgical resection. In this context, we analyzed various clinical characteristics and the long-term survival rate in young patients surgically treated for lung cancer and compared the data with the findings in older patients treated during the same period.

mor, adenoid cystic carcinoma, and mucoepidermoid carcinoma).Thus, a total of 690 patients (524 male and 166 female) were analyzed. Resected specimens were examined pathologically for tumor type and determination of the extent of lymph node spread. The pathological stages were determined according to the TNM classificationrevised in 1986 [8]. An incomplete resection means that there was macroscopic evidence of tumor or metastatic lymph node left behind, microscopic evidence of the tumor on the resected stump, or clinical evidence of distant metastasis. Smoking history was based on the index of Brinkman and Coates (91, that is, the sum of the number of cigarettes smoked per day multiplied by the years of smoking. The data from a total of 683 patients, excluding 7 patients who died within 30 days of operation, were statistically analyzed for the survival rates using the Kaplan-Meier estimated survival curves, and the significance of the difference was analyzed by the generalized Wilcoxon test. Results were considered to be significant if p was less than 0.05.

Material and Methods We retrospectively reviewed the medical records of 22 patients 40 years old or younger at the time of diagnosis with primary lung cancer surgically treated from 1974 to 1989 at the Department of Surgery 11, Faculty of Medicine, Kyushu University. During this period, a total of 699 patients with lung cancer were surgically treated. This study excluded 9 patients who were histologically diagnosed as having a low-grade malignancy (carcinoid tuAccepted for publication Aug 13, 1991. Address reprint requests to Dr Sugio, Department of Surgery 11, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan. 0 1992 by

The Society of Thoracic Surgeons

Results Patient Profile Of the 690 patients surgically treated, 22 (3.2%)were 40 years old or younger (Table 1).The age distribution was 23 to 40 years in the young group (average, 37.4 years) and 41 to 86 years in the control group (average, 63.7 years). The median age was 39 years in the young group and 64 years in the control group. The young group consisted of 12 men and 10 women (1.2:l). The control group of 668 patients consisted of 512 men and 156 women (3.3:l). This ratio was significantly different from the 1.2:l ratio among the young group (p c 0.05). 0003-4975/92/$3.50

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SUGIO ET AL LUNG CANCER IN YOUNG ADULTS

Table 1 . Distribution of Patients According to Age and Histology" Age (Y 1

Squamous Cell

Adenocarcinoma

21-30 31-40 41-50 51-60 61-70 71-80 81+

Total a Numbers

Large Cell

Small Cell

Other

Total

...

...

...

...

...

...

...

1 (2.4) 11 (5.4) 7 (2.6) 8 (5.5) 1 (8.3)

l(2.4) 7 (3.5) 4 (1.5) 3 (2.1) l(8.3)

1 21 41 202 268 145 12

28 (4.1)

16 (2.3)

690

1(100) 12 (57.1) 22 (53.7) 106 (52.2) 127 (47.4) 65 (44.8) 4 (33.3)

7 (17.1) 62 (30.7) 112 (41.8) 58 (40.0) 3 (25.0)

9 (42.9) 10 (24.4) 16 (7.9) 18 (6.7) 11 (7.6) 3 (25.0)

337 (48.8)

242 (35.1)

67 (9.7)

in parentheses are percentages.

The patients in the young age group are summarized in Table 2. Of the 22 patients, 10 were symptomatic; the most common symptoms were cough, hemosputum, and chest pain. The duration of symptoms ranged from less than 1 month to 7 months, and the average duration of symptoms was 3.6 months. The remaining 12 patients were asymptomatic: 10 patients were discovered by incidental routine chest roentgenograms, and 2 were discovered by chest roentgenograms done for the follow-up of other diseases. Three of the asymptomatic patients had a delay of from 9 to 18 months before the diagnosis of lung cancer was made because they had been treated as having

pulmonary tuberculosis after the detection of their lesion on chest roentgenograms. In the young group, 10 patients (45%) were smokers, but only 3 patients had a Brinkman index of greater than 800.

Histology and Stage of Disease There were 13 patients with adenocarcinoma and 9 patients with large cell carcinoma. Table l shows the distribution of patients according to age and tumor type. No significant difference was observed in the frequency of patients with adenocarcinoma in each age decade. How-

Table 2 . Lung Cancer in Young Adults Age (y) 38 38 40 39 40 40 23 35 34 37 39 35 39 40 40 39 32 39 39 40 40 36 a

Sex

Symptoms

F M M F F F M M F F M M M F F M M M M F F M

(-1 (4

Dead of disease.

Chest pain Hemosputum Cough

(4 (-1 (-1 Cough Chest pain Hemosputum Cough

(-1 (4 (-1 Chest pain Chest pain Hemosputum

(-1 (-1 (4 (-1

TNM

Cell Type

Operation

Type of Resection

Survival (mo)

T2N3MO TlN2MO T2N2MO T2NOMO T2N2MO T4NlM1 TlNOMO T2N2MO T2N2MO T3N2MO T4N2MO T4N2MO T4N2MO T4NOMO T2N2MO T3NOMO T3NOMl T3N2MO TZNOMO TlNOMO TlN2MO TlNOMO

Adenocarcinoma Adenocarcinoma Large cell Large cell Large cell Adenocarcinoma Adenocarcinoma Adenocarcinoma Large cell Large cell Large cell Large cell Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Large cell Large cell Adenocarcinoma Adenocarcinoma Adenocaranoma Adenocarcinoma

Lobectomy Lobectomy Pneumonectomy Lobectomy Segrnentectomy Exploratory Lobectomy Lobectomy Lobectomy Lobectomy Exploratory Bilobectomy Lobectomy Lobectomy Lobectomy Partial Lobectomy Lobectomy Lobectomy Lobectomy Lobectomy Lobectomy

Complete Complete Complete Complete Complete Exploratory Complete Incomplete Complete Complete Exploratory Incomplete Incomplete Incomplete Complete Incomplete Incomplete Complete Complete Complete Complete Complete

24" 33" 33" 138 7" 27" 122 45" 82 82 4" 13" 15" 30" 49 11" 43 43 39 37 37b 22

Brinkman Index 0 0 0 0 0 0 0

170 0 160 610 50 190 0 240 1000 800 0 840 200 0 0

Alive with pulmonary metastasis.

Ann Thorac Surg

SUGIO ET AL LUNG CANCER IN YOUNG ADULTS

1992;53:12731

Table 3 . Distribution of Patients According to TNM Classification by Age Group" Stage and TNM

I1 IIIa IIIb IV

Control Groupb

Total

5 (23)' 0 10 (45)c

312 (47)

317 (46)

46 (7)

46 (7)

163 (25) 69 (10)

173 (25) 74 (11)

38 (6)

40 (6)

206 (31) 272 (41) 74 (11) 76 (11) 380 (57) 70 (11) 170 (26)

211 (31) 280 (41) 78 (11) 81 (12) 388 (56) 71 (10) 182 (26)

The 3-year survival rate after complete resection in the young group was 66.2% as compared with 65.2% for patients in the control group ( p = 0.3380). Table 5 shows survival rates stratified according to histological type of the tumor or stage; there was no significant difference between the young group and the control group. Ten of 14 patients with complete resection are presently alive. All 5 patients with NO disease are free of cancer; of 5 patients with N2 disease, 4 are free of cancer and only 1 has recurrent pulmonary metastasis. The 1-year and 3-year survival rates were 83.3% and 33.3% after incomplete resection in the young group.

7 (1) 590 (88)

8 (1) 610 (88)

Comment

38 (6)

40 (6)

5 (23) 2 (9)

TNM T1

T2 T3 T4 NO N1 N2 N3 MO M1

Forty patients were not * Numbers in parentheses are percentages. classified. 'Significance: p < 0.05. p < 0.01 between the two groups.

ever, the high frequency of patients with squamous cell carcinoma more than 51 years of age was statistically significant ( p < 0.01), and the high frequency of patients with large cell carcinoma less than 50 years of age was statistically significant ( p < 0.01), which showed that squamous cell carcinoma was more common in older patients. Patient staging was evaluated by age group (Table 3). In the young group, 5 patients had stage I disease, 10 had stage IIIa disease, 5 had stage IIIb disease, and 2 had stage IV disease. Significant differences were observed in these stages between the young group and control group. Significant differences were observed in the incidence of NO and N2 disease between the young group and the control group. There were no significant differences between the young group and the control group with respect to type of resection (Table 4). In the young group, 14 patients (64%) had a complete resection, 6 patients (30%) had an incomplete resection, and 2 patients (9%) had an exploratory thoracotomy. The causes of incom-

Table 4 . Distribution of Patients According to Type of Resection by Age Group" Type of Resection Complete Incomplete Exploratory a

plete resection or exploratory thoracotomy were malignant effusion proved by cytological examination (T4) in 3 patients, distant metastasis (intrapulmonary, brain) in 2 patients, marked invasion to chest wall (T3) in 1 patient, marked invasion to mediastinum (T4) in 1 patient, and unresectable mediastinal lymph node (N2) in 1 patient.

Young Group

Stage

I

129

Young Group

Control Group

14 (64) 6 (27) 2 (9)

484 (72) 113 (17) 71 (11)

Numbers in parentheses are percentages.

Total 498 (72) 119 (17) 73 (11)

Survival

Most previous studies [3-7,lO-131 on young patients with lung cancer have emphasized the relatively high incidence of female patients, the high incidence of smokers, the high incidence of adenocarcinoma and paucity of patients with squamous cell carcinoma, the high incidence of advanced stage of disease at the time of diagnosis, and the poorer prognosis in young patients than for the older patients with lung cancer. It has also been reported, however, that there is no significant difference in survival rates between young and older patients [3, 4, 111. The male to female ratio in other reports has varied from 1.59 to 3.3:l [ P 7 , 11, 131. In this report, the male to female ratio was 1.2:1, whereas the ratio in the control group was 3.1:l. One of the reasons for the relative increase of female patients in this study is that there was no patients less than 40 years old with squamous cell carcinoma, because almost all patients with squamous cell carcinoma were male (male to female ratio, 11:l).Several studies have reported that smoking was an important factor in the occurrence of lung cancer in young people, and the reason for the relative increase in the number of women among the young patients is the increase of smokers among women [5, 111. The histological type that has a close association with smoking is squamous cell carcinoma or undifferentiated carcinoma, not adenocarcinoma [14, 151. However, only 3 of our patients were heavy smokers who had a Brinkman index greater than 800, and they were male. Therefore, the increase in smokers is not thought to be a reason for the increase of lung cancer in young female patients. Clearly, smoking is an important factor in occurrence of lung cancer for the general population, but it is also necessary to consider other environmental or genetic factors as previously suggested [16], especially in young patients with lung cancer. In young patients, a high incidence of adenocarcinoma and undifferentiated carcinoma was found in some series.

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SUGIO ET AL LUNG CANCER IN YOUNG ADULTS

Table 5. Survival Rates in Young and Control Group” Survival Rates (%) Variable Complete resection Young (14) Control (477) Adenocarcinoma Young (8) Control (237)

Large cell carcinoma Young (6) Control (35) Stage I Young (5) Control (308) Stage I11 (IIIa, 11%) Young (9) Control (126)

Incomplete resection Young (6) Control (112) Exploratory thoracotomy Young (2) Control (69) a

1

2

3

4

5

P

Year

Year

Year

Year

Year

Value

92.9 90.8

85.1 75.6

66.2 65.2

66.2 59.4

66.2 53.7

0.3380

100 94.0

85.7 77.7

64.3 64.5

64.3 57.1

64.3 51.3

0.3850

83.3 79.0

83.3 75.6

66.7 75.6

66.7 70.6

66.7 70.6

0.8561

100 95.6

100 86.5

100 77.8

100 72.3

100 68.0

0.2189

88.9 84.2

77.8 55.6

51.9 42.9

51.9 39.0

51.9 31.1

0.1564

83.3 50.0

50.0 35.6

33.3 23.1

0 19.4

...

50.0 34.6

50.0 8.4

0 6.3

...

...

6.3

17.9

6.3

0.1615

0.7840

Numbers in parentheses are numbers of patients.

Neuman and associates [6] reported that the relative incidence of adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma was 37%, 8%, 24%, and 28%, respectively. DeCaro and Benfield [4] reported 49%, 17%, 29%, and 13%, respectively, and Pemberton and colleagues [13] reported 32%, 27%, 21%, and 13%,respectively. However, almost all cases of small cell carcinoma in these studies were not resected. We had no resected cases of small cell carcinoma, and the reason for this was thought to be their advanced stage at diagnosis. Our study showed that squamous cell carcinoma occurs mainly after the sixth decade of life. It seems reasonable to conclude that squamous cell carcinoma occurs less frequently in young people because of the requirement for longer exposure to carcinogens. The high incidence of advanced stage of disease at diagnosis in young patients has been shown in this study, as has been commonly mentioned in many previous studies [5, 7, 131. Of 12 asymptomatic patients, 5 had stage I disease and 7 had stage III disease, and 5 patients with stage I disease are still alive and well. In contrast, all symptomatic patients except 1had stage III or IV disease. Although almost all reported cases of lung cancer in young patients were symptomatic [4,5, 7,131, our symptomatic cases were not as numerous. However, the fact that 7 of 12 asymptomatic cases had advanced stage with nodal involvement suggests that young people may have unknown factors that accelerate the growth and progression of lung cancer.

Several reports suggest that lung cancer in young patients is more rapidly fatal than that occurring in older patients [6, 71. However, recently it was reported that there is no significant difference in the survival rates between young and older patients [3, 41. DeCaro and Benfield [4] reported that young patients who were not operated on survived for a significantly shorter time than did older patients, but the 5-year survival rates of young patients were not different from older patients in the operative cases. Pemberton and associates [13] reported that the 1-year and 2-year survivals were 71% and 35% after curative resection and 79% and 28% after palliative resection. However, they did not show the survival rates of older patients. We found no significant difference in the survival rates between young and older patients. Therefore, it is reasonable to conclude that the prognosis of young patients with lung cancer was not different from older patients. Currently, complete resection is the only modality to arrest the disease and is required to achieve a better prognosis in patients with lung cancer. Young patients have a good performance status to tolerate surgical treatment or adjuvant therapy at a lower risk, as previously reported [17]. Even in cases of incomplete resection or exploratory thoracotomy, 4 of 8 patients had been alive more than 2 years with chemotherapy or radiation therapy after operation. These results suggest that, despite the advanced stage of disease, better survival is expected in young adults.

Ann Thorac Surg 1992;53:12731

SUGIO ET AL LUNG CANCER IN YOUNG ADULTS

We thank Dr Brian T. Quinn for critical comments. 10.

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Surgically resected lung cancer in young adults.

Twenty-two patients, 40 years old or younger, were surgically treated for lung cancer between 1974 and 1989. The male to female ratio was 1.2:1. Ten p...
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