Prognostic factors in lung cancer in a dened geographical area

over two decades with a special emphasis on gendercrj_289 91..100

Gunnar Svensson
1,3
, Sven-Brje Ewers
2
, Ola Ohlsson
1
and Hkan Olsson
2,3
1 Department of Medicine, Central Hospital, Kristianstad, Sweden
2 Department of Oncology, University Hospital, Lund, Sweden
3 Department of Cancer Epidemiology, Clinical Sciences, University of Lund, Lund, Sweden
Abstract
Introduction: Many studies over recent decades report an increasing incidence of
lung cancer in female patients. Female gender is often reported as a good prognostic
factor.
Objectives: The aim of the present study was to investigate prognostic factors with
a special emphasis on gender.
Methods: During 19892008, 1497 patients in eastern Scania, a part of southern
Sweden with 202 000 inhabitants, were referred to one Central Hospital and pro-
spectively registered. All patients were grouped into four 5-year periods and were
analysed for occurrence of lung cancer, patient performance status, types and stages
of lung cancer and the relation to gender.
Results: The incidence of lung cancer more than doubled in women. The propor-
tion of adenocarcinomas increased in females and in males to 57% (P = 0.028) and
42% (P = 0.001), respectively, while the frequency of small cell lung carcinomas
(SCLCs) decreased in both genders to approximately 14%. Females had signi-
cantly more frequent stage 1 (16.6%) and higher surgery rate (23.1%) than males
(12% and 18.2%, respectively). Females showed a higher 5-year survival rate than
males (20.1% and 11.5%, respectively; P < 0.001). Patients with non-small cell lung
carcinoma (NSCLC) had a higher 5-year survival rate than those with SCLC(16.5%
and 7.5%, respectively; P < 0.01); however, there was no signicant survival differ-
ence in females between NSCLC and SCLC.
Conclusion: Female patients exhibited longer survival than males for both NSCLC
and SCLC, and this was not explained by a higher frequency of stage 1 or surgery
in NSCLC.
Please cite this paper as: Svensson G., Ewers S.-B., Ohlsson O. and Olsson H.
Prognostic factors in lung cancer in a dened geographical area over two decades
with a special emphasis on gender. Clin Respir J 2013; 7: 91100.
Introduction
In many Western countries, lung cancer is the most
common cause of cancer-related death for both sexes.
Records of unselected patients with lung cancer within
dened geographical areas over specied times have
been recorded over the last few decades in Scandinavia
(19), and the 5-year survival is approximately 10% in
many European countries (10). The patients with
NSCLC have better survival rates than patients with
SCLC (11). In many studies, female patients have
higher survival rates both for non-small cell lung car-
cinoma (NSCLC) and small cell lung carcinoma
(SCLC) compared with males (1115). However, few
studies have analysed the survival differences between
NSCLC and SCLC in males and females (11).
Key words
gender NSCLC prognostic factor
SCLC survival
Correspondence
Gunnar Svensson, MD, Pulmonary Section,
Department of Medicine, Central Hospital,
SE-291 85 Kristianstad, Sweden
Tel: +46 44 3091400
Fax: +46 44 3091404
email: gunnar.a.svensson@telia.com
Received: 09 November 2011
Revision requested: 30 January 2012
Accepted: 27 February 2012
DOI:10.1111/j.1752-699X.2012.00289.x
Authorship and contributorship
Gunnar Svensson designed and performed
the study, collected and analysed the data
and wrote the paper. Sven-Brje Ewers
performed the study and analysed the data.
Ola Ohlsson designed the study, analysed the
data and wrote the paper. Hkan Olsson
analysed the data.
Ethics
The research project was approved by the
Ethical Committee, Lund University
(reg.nr.2009/225), Sweden.
Conict of interest
The authors have stated explicitly that there
are no conicts of interest in connection with
this article.
The Clinical Respiratory Journal ORIGINAL ARTICLE
91 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
The present paper reports the clinical information
for lung cancer (the different types and stages) within
a dened region over two decades (19892008). The
study focused on gender and the differences in various
prognostic factors over four 5-year time periods.
Patients and methods
The referral area and degree of coverage
The eastern part of Scania in southern Sweden con-
tains one Central Hospital and two local hospitals for a
population of approximately 202 000 residents. The
total population numbers for the four 5-year time
periods (19891993, 19941998, 19992003 and 2004
2008) were obtained from Statistiska Centralbyrn
(the Central Bureau of Statistics, Sweden) (16).
The coverage of the total referral area was 85.9%
(1497/1743), while for the north-eastern portion,
91.7% of the area (1370/1494) was covered. In the
south-eastern area (consisting of Simrishamn and
Tomelilla communities), the coverage was only 51%
(127/249) because some patients were sent directly to
the Lund University Hospital, and other patients were
treated at the local hospital (Fig. 1).
The local registry and patient characteristicsf
A local registry of lung cancer patients was consecu-
tively established for all patients diagnosed at or
referred to the Pulmonary Section, Department of
Medicine, Central Hospital, Kristianstad between the
years 19892008. One of the authors (GS) was respon-
sible for patient registration and was involved in the
diagnosis and/or treatment of most of the patients,
ensuring consistency of the data collection.
The local registry lists the type of lung cancer, i.e.
squamous cell carcinoma, small cell carcinoma, adeno-
carcinoma, large cell carcinoma, adenosquamous
cancer, carcinoid tumour, adenoid cystic carcinoma,
others and clinical lung cancer, according to the World
Figure 1. Patients diagnosed with lung
cancer in eastern Scania from
19892008 by number (%), gender,
tumour type and stage [non-small cell
lung carcinoma (NSCLC) 14, small cell
lung carcinoma (SCLC) limited disease
(LD)/ extensive disease (ED)]. Adenoca,
adenocarcinoma; Squamous, squamous
cell carcinoma; Large, large cell
carcinoma; Other, other lung cancer;
Clinical, clinical lung cancer.
Lung cancer in eastern Scania
19892008
n=1743
In registry
n=1497 (85.9%)
39.5% female
Not referred to Central Hospital
n=246 (14.1%)
35% female
SCLC
n=34
LD
n=108 (40.6%)
ED
n=158 (59.4%)
Stage 1
n=207 (16.8%)
Stage 2
n=82 (6.7%)
Stage 3
n=422 (34.3%)
Stage 4
n=520 (42.2%)
Adenoca 49.2%
Squamous 28%
Large cell 6.9%
Other 6.2%
Carcinoid 1.7%
Clinical 8%
NSCLC
n=212
SCLC
n=266 (17.8%)
39.5% female
NSCLC
n=1231 (82.2%)
39.6% female
Lung cancer survival in relation to gender Svensson et al.
92 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
Health Organization classication (WHO 1981) (17).
The date of diagnosis was set as the time when data
from the pathological classication were available.
The tumour-node-metastasis classication and
staging (14) for NSCLC were established according
to the international staging system for lung cancer of
1986 (18). Revision of the staging system was per-
formed in 1997 (19), when T3N0 tumours were reclas-
sied from 3A to 2B. For primary operated patients
with NSCLC, the pathological stage was used, while in
others, the clinical stage was applied. In SCLC, the
Veterans Administration staging system (20) of limited
disease (LD) and extensive disease (ED) was used.
The patient performance status at diagnosis was
recorded according to Eastern Cooperative Oncology
Groups (ECOG) 04, where 0 = normal activity
without restriction; 1 = restricted in terms of physi-
cally strenuous activity, but ambulatory; 2 = ambula-
tory and capable of all self-care, although unable to
perform any work, up and about more than 50% of
waking hours; 3 = capable of only limited self-care,
conned to bed or chair more than 50% of waking
hours and 4 = cannot perform any self-care, com-
pletely conned to bed or chair (21). The performance
status group was recorded in the registration form, and
the description of patient activity levels and symptoms
was recorded in the hospital medical record.
The data on missing patients with lung cancer in the
area of our study were obtained from the Regional
Tumour Registry in Lund. Only the lung cancer types
were available, and these patients were only used and
included in the incidence analysis. The time of death
for patients not in the registry was acquired from the
population registry. Lung cancer diagnoses were per-
formed during an autopsy for 18.3% (45/246) of the
patients not referred to our hospital. The times of
referral and the types of examinations have only been
recorded since 1995.
Examinations (data registered 19952008,
n = 1091)
Bronchoscopy was performed in 77% of patients with
localised disease (stages 13 and LD) and in 60% of
patients with advanced disease (stage 4 and ED). A
lung biopsy was performed on 18% of the patients.
Other biopsies (lymph node, pleura, liver, adrenal
gland, bone, skin, muscle) were performed in 20% of
the patients. A computed tomography (CT) of the
thorax and upper abdomen was performed in 98%
of the patients. Sixty-four per cent had scintigraphy or
magnetic resonance imaging (MRI) of the skeleton.
Histological diagnoses were accomplished in 59% of
NSCLC patients and in 63% of patients with SCLC.
Cytology was the basis for diagnosis in 41% of the
patients with NSCLC and in 37% of those with SCLC.
Clinical diagnoses, based only on repeated chest X-rays
or CT of the thorax with no histological or cytological
conrmation, were attained in 5% of the patients.
Positron emission tomography (PET) scanning was
performed on 60 patients during 20042008.
Statistical analyses
The chi-squared test was used for statistical compari-
sons between different factors (age, gender, tumour
type and stage, time delays and time periods). The
MannWhitney two-sided test was used for the com-
parison of two groups, and the KruskalWallis two-
sided test was used for multiple groups. A chi-squared
test for trend was used to evaluate trends in propor-
tions over the time periods. Survival was analysed
using KaplanMeier survival curves and life tables, and
differences were assessed by the two-sided log-rank
test. Univariate and multivariate prognostic factors
(gender, age, performance status, stage, primary
therapy and, in NSCLC, lung cancer type) were analy-
sed with a Cox proportional hazard regression. All
patients were followed until 2009-07-01 or until death.
Statistica version 10.0 (StatSoft, Tulsa, OK, USA) was
used for all statistical analyses.
Results
The incidence of lung cancer in eastern Scania
(n = 1743)
The total incidence of lung cancer increased from 40.0/
100 000 [95% condence interval (CI), 36.344.1]
during the period 19891993 to 49.5/100 000 (95% CI,
45.353.9) during 20042008. There was a slight
decrease in lung cancer occurrence in males from 59.4/
100 000 (95% CI, 52.966.4) during the period of
19891993 to 53.1 (95% CI, 47.059.7) during 2004
2008. However, the incidence of lung cancer in female
patients more than doubled from 21.1/100 000 (95%
CI, 17.425.4) to 45.9 (95% CI, 40.352.1) during the
same time periods (Fig. 2).
Gender and age
Of the 1497 patients in the registry, a total of 39.5%
(n = 592) were female (Fig. 1). The relative frequency
of females with lung cancer increased signicantly
from 26.2% during the period 19891993 to 47.9%
during 20042008 (Tables 1 and 2, P = 0.017). The
Svensson et al. Lung cancer survival in relation to gender
93 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
frequency of males with lung cancer 70 years of age
(55.4%) was signicantly higher than in females
(43.5%; P = 0.005).
The age of the male patients with lung cancer [mean
70 years, median 71 (range 3994)] was signicantly
higher than in females [mean 66.5, median 67 (range
1992); P < 0.001] and remained nearly constant over
all time periods. In females, the percentage of patients
below 60 years of age decreased signicantly from
36.8% in the rst time period to 20.3% in the last time
period (Tables 1, P = 0.026).
Types of lung cancer
In this cohort (n = 1497), adenocarcinoma was the
most frequent type of lung cancer in females (50.2%)
and in males (34.1%; P < 0.001). Adenocarcinoma fre-
quency increased signicantly in both genders during
the time periods (Tables 1 and 2).
The percentage of squamous cell carcinomas
showed a non-signicant decrease in males from
19891993
0
10
20
30
I
n
c
i
d
e
n
c
e

/

1
0
0

0
0
0
40
50
60
70
Female Male Female Male Female Male Female Male
19841998 19892003 19842008
Figure 2. Lung cancer incidence/100 000 in females and in
males in eastern Scania from 19892008 (n = 1743).
Table 1. Female patient characteristics at the time of diagnosis over two decades (19892008); number (percentage)
19891993 19941998 19992003 20042008 Total P
Age
<60 32 (36.8) 29 (24.8) 45 (27.1) 45 (20.3) 151 (25.5) 0.026
6069 27 (31.0) 33 (28.2) 49 (29.5) 75 (33.8) 184 (31.1) 0.708
7079 21 (24.1) 44 (37.6) 50 (30.1) 76 (34.2) 191 (32.3) 0.180
80 7 (8.1) 11 (9.4) 22 (13.3) 26 (11.7) 66 (11.2) 0.570
Lung cancer type:
Squamous 13 (14.9) 16 (13.7) 22 (13.3) 31 (14.0) 82 (13.9) 0.986
Adenocarcinoma 38 (43.7) 49 (41.9) 83 (50.0) 127 (57.2) 297 (50.2) 0.028
Large cell 4 (4.6) 4 (3.4) 17 (10.2) 9 (4.1) 34 (5.7) 0.033
Small cell 23 (26.4) 25 (21.4) 24 (14.5) 33 (14.9) 105 (17.7) 0.045
Carcinoid 1 (1.2) 6 (5.1) 7 (4.2) 2 (0.9) 16 (2.7) 0.055
Other* 3 (3.5) 7 (6.0) 6 (3.6) 12 (5.4) 28 (4.7) 0.705
Clinical 5 (5.8) 10 (8.6) 7 (4.2) 8 (3.6) 30 (5.1) 0.235
Stage
1 10 (11.5) 26 (22.2) 23 (13.9) 39 (17.6) 98 (16.6) 0.147
2 4 (4.6) 4 (3.4) 6 (3.6) 12 (5.4) 26 (4.4) 0.789
3 17 (19.5) 24 (20.5) 42 (25.3) 58 (26.1) 141 (23.8) 0.489
4 33 (37.9) 38 (32.5) 71 (42.8) 80 (36.0) 222 (37.5) 0.330
LD 13 (14.9) 13 (11.1) 10 (6.0) 13 (5.9) 49 (8.3) 0.027
ED 10 (11.5) 12 (10.3) 14 (8.4) 20 (9.0) 56 (9.5) 0.859
Performance status
01 56 (64.4) 65 (55.6) 81 (48.8) 107 (48.2) 309 (52.2) 0.048
2 11 (12.6) 21 (18.0) 42 (25.3) 72 (32.4) 146 (24.7) 0.0007
3 12 (13.8) 12 (10.3) 20 (12.1) 24 (10.8) 68 (11.5) 0.855
4 8 (9.2) 19 (16.2) 23 (13.9) 19 (8.6) 69 (11.7) 0.125
Primary therapy
Any surgery 18 (20.7) 32 (27.4) 36 (21.7) 51 (23.0) 137 (23.1) 0.647
Any radiotherapy 40 (46.0) 37 (31.6) 55 (33.1) 80 (36.0) 212 (35.8) 0.150
Any chemotherapy 39 (44.8) 37 (31.6) 84 (50.6) 148 (66.7) 308 (52.0) <0.001
No therapy 18 (20.7) 30 (25.6) 38 (22.9) 38 (17.1) 124 (21.0) 0.273
*Includes adenosquamous and adenocystic cancer.
Not histologically or cytologically conrmed diagnosis of lung cancer.
ED, extensive disease; LD, limited disease (ED and LD applies only to small cell lung carcinoma).
Lung cancer survival in relation to gender Svensson et al.
94 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
33.5% during the period 19891993 to 24.9% during
20042008; however, its proportion in males is still
signicantly higher than in females (P < 0.001). The
percentage of SCLC patients decreased in both females
and males from 26.4% and 22.5%, respectively, during
19891993 to 14.9% and 14.1%, respectively, during
20042008 (females, P = 0.045; males, P = 0.085). A
clinical diagnosis (repeated chest X-ray or CT without
histology) was signicantly more frequent in patients
aged 60 years (8%) compared with those aged < 60
(2%; P = 0.003). There were 21 carcinoid tumours (16
in females, ve in males, P = 0.0005) during the entire
study period (19892008).
Stages
There was no signicant difference in the frequency
of the exams (bronchoscopy, CT thorax and upper
abdomen, scintigraphy or MRI of skeleton or lung
biopsy) between females and males in the various lung
cancer stages.
Stage 1 NSCLC was found in 16.8% of the pati-
ents, stage 2 was found in 6.7% and stage 3 was
present in 34.3% (Fig. 1). These percentages appeared
fairly constant over time in both females and
males (Tables 1 and 2). The percentage of NSCLC
stage 4 tumours increased signicantly in males
from 24.1% during 19891993 to 41.5% during
20042008 (P = 0.0003). The occurrence of SCLC
stage LD decreased signicantly in both genders
during the time periods (P = 0.027 females,
P = 0.00006 males). Stage 1 NSCLC was more fre-
quent in females (16.6%) than in males (12.0%;
P = 0.013), and stage 3 tumours were observed more
frequently in males (31.1%) than in females (23.8%;
P = 0.002).
Table 2. Male patient characteristics at the time of diagnosis over two decades (19892008); number (percentage)
19891993 19941998 19992003 20042008 Total P
Age
<60 42 (17.1) 27 (13.3) 34 (15.7) 24 (10.0) 127 (14.0) 0.117
6069 74 (30.2) 56 (27.6) 65 (30.1) 82 (34.0) 277 (30.6) 0.525
7079 88 (35.9) 98 (48.3) 75 (34.7) 92 (38.2) 353 (39.0) 0.018
80 41 (16.7) 22 (10.8) 42 (19.4) 43 (17.8) 148 (16.4) 0.092
Lung cancer type
Squamous 82 (33.5) 64 (31.5) 57 (26.4) 60 (24.9) 263 (29.1) 0.129
Adenocarcinoma 64 (26.1) 62 (30.5) 82 (38.0) 101 (41.9) 309 (34.1) 0.001
Large cell 17 (6.9) 6 (3.0) 22 (10.2) 6 (2.5) 51 (5.6) 0.0009
Small cell 55 (22.5) 38 (18.7) 34 (15.7) 34 (14.1) 161 (17.8) 0.085
Carcinoid 2 (0.8) 2 (1.0) 1 (0.5) 0 5 (0.6) 0.500
Other* 8 (3.3) 12 (5.9) 7 (3.2) 21 (8.7) 48 (5.3) 0.022
Clinical 17 (6.9) 19 (9.4) 13 (6.0) 19 (7.9) 68 (7.5) 0.604
Stage
1 32 (13.1) 27 (13.3) 25 (11.6) 25 (10.4) 109 (12.0) 0.749
2 19 (7.8) 15 (7.4) 8 (3.7) 14 (5.8) 56 (6.2) 0.274
3 80 (32.7) 62 (30.5) 71 (32.9) 68 (28.2) 281 (31.1) 0.670
4 59 (24.1) 61 (30.1) 78 (36.1) 100 (41.5) 298 (32.9) 0.0003
LD 31 (12.7) 11 (5.4) 10 (4.6) 7 (2.9) 59 (6.5) 0.00006
ED 24 (9.8) 27 (13.3) 24 (11.1) 27 (11.2) 102 (11.3) 0.712
Performance status
01 126 (51.4) 112 (55.2) 112 (51.9) 96 (39.8) 446 (49.3) 0.006
2 55 (22.5) 36 (17.7) 47 (21.8) 71 (29.5) 209 (23.1) 0.028
3 34 (13.9) 29 (14.3) 27 (12.5) 39 (16.2) 129 (14.3) 0.729
4 30 (12.2) 26 (12.8) 30 (13.9) 35 (14.5) 121 (13.4) 0.885
Primary therapy
Any surgery 48 (19.6) 48 (23.6) 42 (19.4) 27 (11.2) 165 (18.2) 0.006
Any radiotherapy 109 (44.5) 77 (37.9) 68 (31.5) 80 (33.2) 334 (36.9) 0.016
Any chemotherapy 63 (25.7) 59 (29.1) 107 (49.5) 138 (57.3) 367 (40.6) <0.001
No therapy 78 (31.8) 54 (26.6) 59 (27.3) 66 (27.4) 257 (28.4) 0.575
*, ED, LD; See Table 1.
Svensson et al. Lung cancer survival in relation to gender
95 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
Performance status
The frequency of performance status 1 decreased and
the frequency of performance status 2 increased sig-
nicantly in both genders during the time periods
(Tables 1 and 2). The performance distribution
became signicantly worse in males from 19891993
to 20042008 (P = 0.043). However, in comparison
with females, the performance status in males was sig-
nicantly worse only in the last period (P = 0.017).
Time delay (data registered 19952008, n = 1091)
The time lag from referral to the onset of treatment
was signicantly shorter for NSCLC patients present-
ing with a more advanced-stage tumour (P < 0.001).
Approximately 45% of patients with stage 4 tumours
were treated within 4 weeks of referral, while in
patients displaying stages 12, only approximately 5%
were treated within 4 weeks. Sixty-eight per cent of the
patients diagnosed with SCLC were treated within 4
weeks, and there were no differences between the LD
and the ED patients in that respect. There was no sig-
nicant difference between males and females in the
time to treatment for the different tumour stages.
Gender-related survival
Female patients in the registry demonstrated a signi-
cantly (P < 0.001) higher 5-year survival rate than male
patients in NSCLC (21.2% and 13.5%, respectively;
P = 0.0002) and in SCLC (15.6% and 2.6%, respec-
tively; P < 0.001; Fig. 3). In females, there was no sig-
nicant difference in long-term survival between
NSCLC and SCLC patients during any time period.
In males, there was a signicantly better survival rate
in patients with NSCLC compared with SCLC
(P = 0.001); however, in the different time periods, this
difference in survival was signicant only during the
19992003 time frame.
Multivariate analyses
In the multivariate analyses of prognostic factors for
NSCLC, male gender, performance status >1, stage >2,
other lung cancer type and therapy without surgery or
no therapy had an increased hazard ratio for death
(Table 3).
In SCLC, male gender, performance status >1, ED
and no therapy were negative prognostic factors
(Table 4).
Survival of all patients diagnosed with lung
cancer in eastern Scania
The 5-year survival of all lung cancer patients in
eastern Scania (n = 1743) was 13.6% (18.7% and
10.4% in females and males, respectively; P < 0.001).
There was no signicant increase in survival over the
time periods for females or for males (log-rank test). In
the 212 patients with NSCLC not referred to Central
Hospital, the 5-year survival was 10.8% and 4.3% in
females and in males, respectively (P = 0.003). Of the
34 patients with SCLC who were not referred to
Central Hospital, none survived for 5 years.
Discussion
There has been an increasing incidence of lung cancer
in females, reported in most European countries (10).
During the last 15 years, lung cancer diagnoses were
more frequent in females aged younger than 60 than
in males younger than 60, which is in agreement with
ndings in the Uppsala/rebro lung cancer registry
during 19952008 (7). The occurrence of lung cancer
in males levelled off after peaking during 19801989,
which is consistent with the study performed by
Janssen-Heijnen and Coebergh(10). The most impor-
tant reason for the increased lung cancer incidence in
females in our study is believed to be the increased
P = 0.0002
0
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
5 10 15 20
Years since diagnosis
C
u
m
u
l
a
t
i
v
e

p
r
o
p
o
r
t
i
o
n

s
u
r
v
i
v
i
n
g
Figure 3. Overall survival of patients with non-small cell lung
carcinoma (NSCLC) and small cell lung carcinoma (SCLC) in
relation to gender in eastern Scania from 19892008
(n = 1497). Log-rank test: NSCLCFemale : NSCLCMale
(P = 0.0002), SCLCFemale : SCLCMale (P < 0.001), NSCLC
Female : SCLCFemale (P = 0.952), NSCLCMale : SCLCMale
(P = 0.001). ( ) NSCLCFemale (n = 487), ( ) SCLCFemale
(n = 105), ( ) NSCLCMale (n = 744), ( ) SCLCMale
(n = 161).
Lung cancer survival in relation to gender Svensson et al.
96 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
prevalence of smoking in females in the 1970s (22).
Other reasons might be increased susceptibility to
carcinogens and a decreased DNA repair capacity
reported in females (23).
The incidence of lung cancer during 20042008
reported here was somewhat higher than that previ-
ously reported in southern Sweden during 20002007
(8). This discrepancy may be because of the differences
in districts and in time periods. Furthermore, some
patients with clinical lung cancer types were not
reported to the Swedish Cancer Registry, as described
by Barlow L et al. (24).
The relative frequency of adenocarcinomas in-
creased signicantly in both genders, while the rates of
SCLC decreased in females and males (signicantly in
females). These trends have previously been observed
in many countries, as reported in a database study
performed by the International Agency for Research on
Cancer (25).
The percentage of tumours in stages 13 in NSCLC
patients was mainly stable over time. The increase in
the relative frequency of stage 4 tumours in males was
signicant; such a trend was also noticed in selected
patients at the MD Anderson Cancer Center (26) and
may be because of more efcient CT scanners and
CT-guided biopsies during the later years as well as
the utilisation of PET scanning during the last 5
years.
Table 3. Univariate and multivariate analyses of prognostic factors for survival in
non-small cell lung carcinoma (n = 1231) in eastern Scania from 19892008
Univariate Multivariate
HR 95% CI P HR 95% CI P
Gender
Female (n = 487) 1.00 ref 1.00 ref
Male (n = 744) 1.27 1.141.40 0.0002 1.21 1.061.37 0.005
Age
<60 (n = 217) 1.00 ref 1.00 ref
6069 (n = 374) 1.18 0.991.36 0.089 1.07 0.891.30 0.467
7079 (n = 453) 1.31 1.041.58 0.003 0.96 0.791.17 0.706
80 (n = 187) 2.13 1.922.35 <0.001 0.96 0.761.23 0.764
Performance status
01 (n = 639) 1.00 ref <0.001 1.00 ref <0.001
2 (n = 281) 3.23 3.073.39 2.10 1.772.48
3 (n = 152) 6.35 6.166.55 2.99 2.403.73
4 (n = 159) 16.3 16.116.5 7.08 5.598.98
Lung cancer type:
Squamous cell
carcinoma
(n = 345)
1.00 ref 1.00 ref
Adenocarcinoma
(n = 606)
1.08 0.941.25 0.296 1.04 0.901.21 0.593
Large cell (n = 85) 1.10 0.861.42 0.449 1.25 0.971.62 0.091
Other (n = 76) 1.89 1.462.44 <0.001 1.55 1.192.01 0.001
Carcinoid (n = 21) 0.14 0.060.32 <0.001 0.36 0.160.83 0.017
Clinical (n = 98) 2.01 1.592.54 <0.001 0.84 0.661.08 0.174
Stage
1 (n = 207) 1.00 ref 1.00 ref
2 (n = 82) 1.80 1.482.12 0.0003 1.14 0.821.58 0.440
3 (n = 422) 4.25 4.034.47 <0.001 2.31 1.802.97 <0.001
4 (n = 520) 10.39 10.1610.6 <0.001 4.06 3.105.31 <0.001
Primary therapy:
Any surgery (n = 293) 1.00 ref <0.001 1.00 ref <0.001
Radiotherapy and/or
chemotherapy
(n = 591)
6.48 5.897.94 2.74 2.143.50
No therapy (n = 347) 17.83 14.2622.3 5.08 3.796.81
HR, hazard ratio; CI, condence interval; ref, reference.
Svensson et al. Lung cancer survival in relation to gender
97 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
The time from referral to the onset of treatment was
signicantly shorter in NSCLC patients with more
advanced stages of lung cancer, contradicting the study
by Koyi et al. (27) (who also included SCLC patients)
but in accord with the ndings of Myrdal et al. (28).
The shorter time lag could be because of the increased
number of affected patients with increased biopsy
possibilities, and thus, most of these patients received
chemotherapy with a shorter delay. It could not be
excluded that early treatment for the lower tumour
stages can have positive impact on patient long-term
prognosis. However, in a study by Skaug et al., the
length of delay for patients undergoing surgery had no
inuence on survival (9).
Our observations of the improved survival in female
patients compared with males in both NSCLC and
SCLC corroborate other reports (1115). The good
survival rates of the female SCLC patients are com-
parable with the survival of females with NSCLC.
However, in males, there was a signicantly worse
long-term survival for patients with SCLC compared
with males with NSCLC. This reects the low 5-year
survival rate in male patients with SCLC (2.6%).
A possible reason for the improved survival for
female patients could be the lower median age in
females (67) compared with males (71); however, age
(in decades) was not a prognostic factor in the multi-
variate analysis. Another reason could be the slightly
worse performance status distribution in males, and
this could reect increased co-morbidity in male
patients; however, co-morbidity was not recorded.
Smoking status could also inuence survival; however,
it was also not recorded. Females have been reported to
present with earlier stages of the disease (29), and stage
1 NSCLC was more frequent in our female patients
(16.6%) than in males (12%). Only stage 3 tumours
were signicantly more frequent in male patients than
in females.
Carcinoids are known to be more frequent in female
patients than in males. It is also known that patients
with carcinoids have a favourable prognosis compared
with other lung cancer types (30). Carcinoids were
included in our survival analysis of NSCLC; however,
even if they were excluded, the signicant prognosis
advantage remains for female patients with NSCLC.
Treatment with surgery is an important prognostic
factor in NSCLC, and the surgery rate was signicantly
higher in females (23.1%) than in males (18.2%;
P = 0.021), which is a nding also reported by Fu et al.
(31).
Table 4. Univariate and multivariate analyses of prognostic factors for survival in small cell
lung carcinoma (n = 266) in eastern Scania from 19892008
Univariate Multivariate
HR 95% CI P HR 95% CI P
Gender
Female (n = 105) 1.00 ref 1.00 ref
Male (n = 161) 1.88 1.612.15 <0.001 1.94 1.472.57 <0.001
Age
<60 (n = 61) 1.00 ref 1.00 ref
6069 (n = 87) 1.65 1.302.00 0.005 1.31 0.921.88 0.138
7079 (n = 91) 1.93 1.582.28 0.0001 1.17 0.811.69 0.401
80 (n = 27) 2.55 2.073.03 0.0001 0.89 0.521.55 0.687
Performance status
01 (n = 116) 1.00 ref <0.001 1.00 ref
2 (n = 74) 2.09 1.782.40 2.03 1.452.84 0.00004
3 (n = 45) 3.21 2.863.57 1.94 1.282.95 0.002
4 (n = 31) 6.89 6.477.31 2.88 1.724.84 0.00006
Stage
LD (n = 108) 1.00 ref 1.00 ref
ED (n = 158) 2.80 2.533.07 <0.001 2.00 1.492.69 <0.001
Primary therapy:
Any surgery (n = 9) 1.00 ref 1.00 ref
Chemotherapy and/or
radiotherapy (n = 223)
3.24 1.427.38 0.005 1.94 0.834.50 0.126
No therapy (n = 34) 20.28 8.2949.63 <0.001 10.9 4.0030.0 <0.001
HR, hazard ratio; CI, condence interval; ref, reference.
Lung cancer survival in relation to gender Svensson et al.
98 The Clinical Respiratory Journal (2013) ISSN 1752-6981
2012 Blackwell Publishing Ltd
Chemotherapy was given to signicantly more
female patients (52%) than males (40.6%; P < 0.001).
More male patients (28.4%) had no active therapy
compared with females (21%; P = 0.001). This discrep-
ancy could be caused by the higher ages and slightly
worse performance status distribution of the male
patients and possibly an increase in co-morbidity in
males.
However, when treatment was included in the mul-
tivariate analyses, female gender was still a good prog-
nostic factor for both NSCLC and SCLC.
Limitations and strengths of the present study
The present study comprises hospital material, where
patients were diagnosed and treated according to con-
temporary national guidelines. However, treatments
have changed over the 20-year study period. In par-
ticular, the use of chemotherapy in patients diagnosed
with advanced NSCLC has increased substantially
since 1995.
The diagnosis date was set at the pathologic reply
date because of a rather long reply delay during the
early 1990s.
Of all lung cancer patients in eastern Scania, 14%
were not referred to our hospital; of these, 18.3% were
diagnosed by autopsy ndings. The remaining patients
were possibly clinically advanced with poor general
health and were therefore not referred. This possibility
is supported by the rather short survival rate of
patients not in the registry.
In 1997, the denition of the lung cancer stages
changed, resulting in a satellite tumour in the same
lobe being dened as T4; earlier, this was not speci-
cally stated and thus may have resulted in a stage M1
classication. T3N0 tumours changed from stage 3A to
2B, which was corrected for in the present study.
Because our local registry did not contain a pathol-
ogy staging system, only patients primarily undergoing
surgery were assigned a pathology stage. In the remain-
ing patients, the stages were based on clinical ndings.
Most of the patients with lung cancer in the 1980s
were smokers or former smokers (32); therefore, we
omitted this information from the registry.
The pathology reports have not been reviewed, and
variations over time between different pathologists
along with variations in histochemical techniques
cannot be completely ruled out as inuential factors in
this study.
Eastern Scania is a well-dened area, exhibiting a
rather small variation in population structure over the
20 years this study entails; this is true when comparing
urban, suburban and rural parts in this respect.
The extended time period of two decades with only
one person involved in the diagnosis and/or treatment
of almost all patients as well as performing all registra-
tions in exactly the same way minimised the risk of
judgement discrepancies.
In conclusion, the present study conrms the
increased incidence of lung cancer in females and the
increased frequency of adenocarcinomas in both
genders. This study also conrms the better survival of
female patients with either NSCLC or SCLC compared
with males. The better prognosis in women is not
explained by the higher frequency of stage 1 tumours
or a higher surgery rate in NSCLC. This study reports
no survival differences for females between NSCLC
and SCLC.
The research project was approved by the Ethi-
cal Committee, Lund University (reg.nr. 2009/225),
Sweden.
Acknowledgements
This research project was nancially supported by the
Medical Research Council, Central Hospital, Kristian-
stad and Kristianstad University.
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