(Chest. 2001;120:32-36.)
© 2001
American College of Chest Physicians
Lung Cancer Treated Surgically in Patients <50 Years of Age*
Hiroya Minami, MD;
Masahiro Yoshimura, MD;
Hidehito Matsuoka, MD;
Sakamoto Toshihiko, MD and
Noriaki Tsubota, MD
*
From the Department of Thoracic Surgery, Hyogo Medical Center for Adults, Akashi City, Hyogo, Japan.
Correspondence to: Noriaki Tsubota, MD, Department of Thoracic Surgery, Hyogo Medical Center for Adults, Kitaohji-cho 13–70, Akashi City 673, Hyogo, Japan; e-mail: n-tsubo{at}sanynet.ne.jp
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Abstract
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Study objectives: Some investigators have suggested
that lung cancer in young patients has a more aggressive course and a
poorer prognosis than lung cancer in older patients. The aim of this
study was to determine if the basal characteristics and survival in
younger patients with lung cancer undergoing surgical resection differ
from those of older patients.
Design: Retrospective
clinical study.
Patients: Of 1,208 consecutive
patients who underwent surgery for primary lung cancer between June
1984 and March 2000, we reviewed the medical records of 110 younger
patients who were < 50 years of age at the time of surgery and
compared them with 1,098 older patients (
50 years of age). All
deaths were included.
Results: In the younger patient
group, asymptomatic disease and adenocarcinoma was significantly more
frequent, the rate of smoking was significantly higher, and the amount
of smoking (Brinkman index) was significantly larger. For the 94
younger patients with complete resection, the 5-year survival rate was
61.0%, which was not significantly higher than that for the 923 older
patients (57.7%). However, the 53 younger patients with stage I
disease (5-year survival of 84.3%) had significantly better survival
than older patients with the same condition (71.6%). Survival of
patients in stage II or stage III disease was not significantly
different.
Conclusion: The younger patients had
significantly better prognoses, and a statistical difference was shown
especially in the early stage, while in the advanced stage the
malignancy of the lung cancer itself surpassed the difference in
survival.
Key Words: age • lung cancer • non-small cell lung cancer • surgery • young
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Introduction
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Lung
cancer is the leading cause of cancer-related mortality in both men and
women. Although most cases of lung cancer occur in the sixth through
eighth decades of life, 5 to 10% are diagnosed in patients < 50
years of age.1
There are characteristic features in young patients with lung cancer
that differ from those in older patients with lung cancer: a relatively
high incidence of female patients and a high incidence of
adenocarcinoma.2
3
4
An impression is widely held that
young patients with lung cancer have a poorer prognosis than older
patients. Many reports2
3
4
5
6
7
8
9
have described survival rates
in lung cancer patients with respect to age. Various investigators have
concluded inferior2
5
6
8
or equivalent4
9
survival for younger compared to older patients, but the results are
controversial and confusing. The purpose of this study was to analyze
various clinical characteristics and long-term survival in younger
patients (< 50 years of age) treated surgically for lung cancer
compared with the older patients during the same period.
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Materials and Methods
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Between June 1984 and March 2000, 1,412 consecutive patients
with non-small cell lung cancer underwent pulmonary resection at our
institution, of whom 204 patients with induction therapy were excluded
from this analysis. Of these 1,208 patients, 110 patients (9.1%)
< 50 years of age at the time of surgery were studied.
Histopathologic diagnosis and staging were carried out according to the
new TNM staging system,10
revised in 1997. In 1,017
patients (94 younger and 923 older patients) with complete resections,
lobectomy was by far the most common procedure and was performed in 763
patients (75.0%), including 104 combined sleeve resections of the
bronchus. Thirty pneumonectomies (2.9%), including 3 sleeve
resections, 176 segmentectomies (17.3%), 45 wedge resections, and 3
bronchial resections, were performed.
In this study, we excluded patients with malignant effusion detected
before the operation. Immediately after thoracotomy, the pleural cavity
was washed with 20 mL of normal saline solution, and a cytologic
examination of the fluid was done. When the report result from the
pathologist was positive, we diagnosed the disease as malignant
effusion (T4)11
12
and changed the complete resection into
a simpler procedure.
Hilar and mediastinal lymph node dissections were routinely performed
in patients with complete resection. The Brinkman index
data13
(the sum of the number of cigarettes smoked per day
multiplied by years of smoking) were recorded for 775 patients (73
younger and 702 older patients; 64.2% of all cases), and there were no
differences in missing data between younger and older patients.
Carcinoembryonic antigen (CEA) was measured before and 1 month after
surgery. The cut-off level for CEA was 5.0 ng/mL.
Data are expressed as the mean ± SE. The 
2
test was used to compare differences between proportions. The
Student’s t test was used for analysis of continuous data.
This study was a retrospective analysis, and follow-up data were
obtained for all patients. Operative mortality rates imply 30-day
postoperative mortality plus intraoperative mortality. Hospital death
was defined as all deaths during initial hospital stay. The survival
rates were estimated using the Kaplan-Meier method in 94 younger
patients and 923 older patients who had complete resection. The
log-rank test was used to compare survival rates. A p value < 0.05
was considered significant. Deaths included those due to cancer,
noncancer, and unknown causes.
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Results
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Of 1,208 lung cancer patients, 110 patients (9.2%) were < 50
years of age at the time of surgery. Within this group of younger
patients, 97 patients (88.2%) were 40 to 49 years of age and only 13
patients (11.8%) were < 40 years of age.
Overall follow-up duration ranged from 5 to 171 months, with a mean of
41 months. The operative mortality rate was 0.33% (4 of 1,208
patients). These four patients died of hemorrhage, pulmonary
infarction, acute myocardial infarction, and brain metastasis,
respectively. Hospital deaths accounted for 1.1% (13 of 1,208
patients): interstitial pneumonia (n = 3), pulmonary fibrosis
(n = 3), pneumonia (n = 2), acute myocardial infarction (n = 2),
respiratory failure (n = 1), pulmonary infarction (n = 1), and
brain metastasis (n = 1) after surgery during the same
hospitalization period.
The difference in the male-to-female ratio was not significant (NS)
between younger and older patients. In the younger patient group,
asymptomatic disease and adenocarcinoma was diagnosed significantly
more frequently, while squamous cell carcinoma was diagnosed
significantly less. The number of smokers was significantly higher and
the amount of smoking (Brinkman Index) was significantly larger in
younger patients (Fig 1
and Table 1 ). However, there was no significant difference in the frequency of
adenocarcinoma histologic subtypes (Table 2
).
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Figure 1.. Patients and histologic type. Adenocarcinoma was
diagnosed significantly more frequently and squamous cell carcinoma
significantly less frequently in the younger patient group
(p < 0.0001). Others, represented by the gray areas, included
adenosquamous carcinoma and unclassified carcinoma.
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For the 94 younger patients in all stages combined with complete
resection, the 5-year survival rate was 61.0%, which was not
significantly higher than that for the 923 older patients with the same
condition (Fig 2
). In the survival of patients with incomplete resection, there was no
significant difference between the two groups (Fig 3 ). Survival of patients with adenocarcinoma was not significantly
different between the younger and the older patients. However, the 53
younger patients with stage I disease had significantly better survival
than the 541 older patients (5-year survival of 84.3% vs 71.6%; Fig 4 ). These differences remained significant in favor of younger patients
even after excluding patients with other causes of death (5-year
survival of 86.3% vs 73.5%; Fig 5
). Survival of patients with stage II or stage III disease was not
significantly different between the younger and the older patients (Fig 4)
. In patients with adenocarcinoma, asymptomatic disease, or
incomplete resection, significant differences were not found between
the two age groups. Survival was not significantly different between
the much younger patients (< 40 years old) and middle-aged patients
( 40 years and < 50 years old).
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Figure 4.. Actual survival curves of 589 patients with stage
I disease according to age. Younger patients had significantly better
survival than older patients (p < 0.01). There was no significant
difference in stage II or stage III disease.
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Figure 5.. Actual adjusted (tumor-related) survival curves of
565 patients with stage I disease according to age. Younger patients
had a significantly better survival than older patients
(p < 0.01).
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Discussion
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In this retrospective study of > 1,200 patients who underwent
lung resection over a 16-year period, some differences concerning age
were found in tumor presentation and prognosis. In our study, 50 years
of age was chosen as the cutoff to ensure adequate numbers of younger
patients to allow for meaningful statistical analyses. The actual
number of patients < 40 years of age was 13 patients (1.1%), and
there was no significant difference in survival between much younger
(< 40 years) and middle-aged patients ( 40 years and < 50 years
old). However, we had the difficulty in comparing our results with
those of previous reports, as the cutoff ages to define "young"
were different in each report.2
3
4
7
9
In the past decade, adenocarcinoma has surpassed squamous cell
carcinoma as the most common histologic subtype of lung
cancer.14
Cigarette consumption was significantly higher
in the older than the younger patients partly because they are living
longer. This difference in smoking resulted in different histology
findings.14
Younger patients had a significantly higher frequency of the
asymptomatic disease. Although de Perrot and colleagues15
attributed the different proportion of asymptomatic disease to the
location of the tumor, this did not hold true in our study, in which
tumor location did not significantly differ between the two groups.
Various investigators have concluded inferior,2
5
6
8
or
equivalent4
9
survival for younger patients compared to
older patients. They compared survival in all stages combined, not
stage by stage. Thus, in the present study of a large number of lung
cancer patients, we compared the survival within each stage. The
morbidity and mortality in the present series were relatively low,
mainly due to the infrequency of pneumonectomy; the survival rate was
acceptable. We performed lung-saving surgery without affecting
prognosis in older and younger patients.
In stage I, younger patients had significantly better prognosis,
although this was not significant for all stages. In adjusted
(tumor-related) survival, the result was the same. These data are
consistent with those from the previous observation of Ramalingam and
colleagues.7
However, the reasons why such age-related
differences exist remain obscure.
We observed that the effect of age was present only in the early stage
and that in the advanced stage the malignancy of the lung cancer itself
erased the difference. Neither was the difference explained by other
differences in lung cancer presentation and management. The results
were considered to be compatible with the clinical impression that
cancers in elderly patients generally grow and progress slower than in
young patients.16
It is also known that the incidence of
many types of cancer increases with age, and that occurrences of two or
three different malignancies in one individual are not uncommon in the
elderly population.17
In this study, there were no
significant differences in the concurrence of different malignancies.
Our findings give further support to the hypothesis that the
immunocompetence of younger patients is superior to that of the older
patients. Indeed, previous experimental studies17
18
19
demonstrated that the same restraint stress resulted in a more serious
influence on the immune cells in old than in young mice. Bohr and
Anderson20
reported that this phenomenon could be
attributed to the accumulation of DNA damages and to the attenuation of
immunosurveillance with age.
In conclusion, the younger patients had significantly better prognoses,
and a statistical difference was shown especially in the early stage,
while in the advanced stage there was no significant difference.
Throughout the course of this article, we refute the notion that
younger patients with lung cancer have a worse prognosis due to more
aggressive tumors.
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Footnotes
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Abbreviation:
CEA = carcinoembryonic antigen; NS = not significant
Received for publication July 17, 2000.
Accepted for publication February 12, 2001.
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Abstract
Introduction
