Depression and Psychological Distress in Patients During the

Year After Curative Resection of NonSmall-Cell Lung Cancer

By Yosuke Uchitomi, Ichiro Mikami, Kanji Nagai, Yutaka Nishiwaki, Tatsuo Akechi, and Hitoshi Okamura
Purpose: There have been few psychosocial studies of
patients after curative resection of nonsmall-cell lung cancer (NSCLC). The purpose of this study was to clarify the
clinical course of depression and psychological distress of
such patients during the year after surgery and to identify
predictors of their long-term outcome.
Patients and Methods: A total of 212 patients completed
assessments during a 12-month follow-up period after curative resection of NSCLC. Psychological measurements at 1, 3,
and 12 months after surgery were conducted using the Structured Clinical Interview for Diagnostic and Statistical Manual
of Mental Disorders (ed 3), Revised, and the Profiles of Mood
States (POMS) scale. Univariate and multivariate analyses
were used to identify predictors of psychological outcome
according to these two methods of assessment.
Results: The prevalence of depression did not change
during the year after curative resection (range, 4.7% to
8.0%). The total POMS score was also unaltered during the

year after surgery: the anger-hostility (P < .001) and tension-anxiety subscale scores (P < .026) had increased at 12
months, but the vigor-activity subscale score had also increased (P < .001). All predictors of psychological outcome
at 12 months included a depression episode after the diagnosis of lung cancer or at 1 month after surgery. Lesseducated status was also a significant predictor of depression at 12 months.
Conclusion: These results suggest the need for psychosocial support even after curative resection of NSCLC and
indicate that an approach that includes repetitive perioperative assessment of depression and careful attention to
less-educated patients might be of benefit to patients in
ameliorating depression and psychological distress during
the year after curative resection.
J Clin Oncol 21:69-77. 2003 by American
Society of Clinical Oncology.

UNG CANCER is the most common form of cancer and the

most common cause of cancer-related deaths in the
world.1,2 Since the 1980s, extensive quality-of-life (QOL) research has been introduced in clinical trials on lung cancer
patients,3,4 but few of these studies have examined psychological
distress after curative resection of nonsmall-cell lung cancer
(NSCLC).5-7 Although surgical treatment for early-stage
NSCLC is generally considered curative, the outcome of NSCLC
is still unsatisfactory: The postoperative 5-year survival rate is
79.0% for patients with pathologic stage IA disease, 59.7% for
those with stage IB disease, 56.9% for those with stage IIA
disease, and 45.0% for those with stage IIB disease.8 There are
survivors after curative resection of NSCLC, despite the overall
grim statistics. The psychological distress of NSCLC patients
after surgery also seems to be less well understood in the context
of curative cancer treatment.3,4
Psychological distress, including depression, is an essential
element of the QOL of cancer patients and, thus, depression has
a great impact on their QOL.9-11 Depression may be associated
with treatment decision making, such as choosing chemotherapeutic agents,12 and with the shorter survival of lung cancer
patients.13,14 Nevertheless, other studies have revealed that
medical staff are poor at detecting emotionally distressed or
depressed cancer patients.15-17
Depression is common in cancer patients and occurs throughout the course of their illness.18-20 Previous reports21-25 on
depression after a diagnosis of lung cancer have revealed that
15% to 44% of patients experience some form of depression,
including major depression and adjustment disorders with depressive mood, on the basis of Diagnostic and Statistical Manual
for Mental Disorders, Revised (DSM-III-R) criteria,26 or clinically probable and borderline depression, on the basis of the
Hospital Anxiety and Depression Scale (HADS).27 Because lung
cancer and its treatment varies with histologic type and disease

stage, previous studies have merely shown that some patients

may experience depression after curative resection of NSCLC.
We therefore first examined the prevalence of depression using
the Structured Clinical Interview for DSM-III-R (SCID)28 in a
large, homogeneous, consecutive, prospectively designed sample of NSCLC patients during the 3 months after curative
resection, and found that the 1-month prevalence of depression at
1, 2, and 3 months after surgery was 9.0%, 9.4%, and 5.8%,
respectively.29 Although the prevalence of depression was lower
than in lung cancer patients as a whole, including patients with
advanced and small-cell lung cancer, it was not so low that it was
negligible (0.9% to 3.7% in the general populations).30-32
Factors associated with psychological distress, including depression, in various cancers have included physical variables,
such as pain, fatigue, other symptom burden, and poor performance
status (PS),25,33-35 whereas other studies have indicated sociodemographic and psychosocial variables, such as younger age36 and
social support, including marital status.37 Because physical variables, such as PS and dyspnea, would be expected to improve by 6
or 9 months after surgery,5-7 psychosocial factors may more

Journal of Clinical Oncology, Vol 21, No 1 (January 1), 2003: pp 69-77

DOI: 10.1200/JCO.2003.12.139

From the Psycho-Oncology Division, National Cancer Center Research

Institute East, and Psychiatry Division, National Cancer Center Hospital
East, Kashiwa, Chiba; Psychiatry Division, National Shikoku Cancer Center, Matsuyama, Ehime; Thoracic Oncology Division, National Cancer
Center Hospital East, Kashiwa, Chiba; and Division of Occupational
Therapy, Institute of Health Sciences, Hiroshima University School of
Medicine, Hiroshima, Japan.
Submitted December 27, 2001; accepted August 20, 2002.
Address reprint requests to Yosuke Uchitomi, MD, PhD, Psycho-Oncology
Division, National Cancer Center Research Institute East, Kashiwanoha
6-5-1, Kashiwa, Chiba 277-8577, Japan; email: yuchitom@east.ncc.go.jp.
2003 by American Society of Clinical Oncology.
0732-183X/03/2101-69/$20.00

69

70

UCHITOMI ET AL

strongly predict depression and psychological distress after curative

resection in NSCLC patients than physical factors.
Previous studies that examined the prevalence of depression
and factors associated with depression in lung cancer patients
have entailed certain drawbacks, such as small sample size,2123,25 a heterogeneous subject population that included subjects
with all histologic types and all disease stages,21-23 measurement
of depression by self-report measures with limited accuracy,23,24,34 and design as a cross-sectional or short-term follow-up
study.21-25,29,34 In this study, we chose to use a structured clinical
interview, after which clinical intervention for psychiatric disorders had to be recommended by feedback to the attending
physician as both a means of clarifying the clinical course of
depression by rigorous methods during the year after curative
resection of NSCLC and a means of identifying factors predictive of long-term outcome. We also used reliable, valid, selfadministered instruments to assess psychological distress during
the year after surgery.
PATIENTS AND METHODS

Participants
Consecutive newly diagnosed patients were invited to participate in the
study after curative resection of NSCLC conducted at the Thoracic Oncology
Division, National Cancer Center Hospital East, Kashiwa, Japan.
The eligibility criteria were 18 years of age or older; awareness of the
diagnosis of cancer; ability to speak Japanese; standard surgical treatment
(lobectomy or pneumonectomy with mediastinal lymph node dissection); no
evidence of brain tumor on computerized tomography or magnetic resonance
images of the head; no history of or current chemotherapy, immunotherapy, or
radiation therapy; no active concomitant cancer; curative resection on the basis
of pathology reports of an International Union Against Cancer (UICC) disease
stage of pT1 to pT3, pN0/1, pM0;38 and no severe medical conditions at 1 month
after surgery.

Procedure
The study was approved by the institutional review board of the National
Cancer Center, Japan. Each patient was fully informed of the purpose of the
study before written consent was obtained. Some demographic and clinical
characteristics, including age, sex, type of surgery (lobectomy or pneumonectomy), preoperative percent vital capacity (%VC), preoperative percent
forced expiratory volume in 1 second (%FEV1), and preoperative PS, were
obtained from the patients medical charts, whereas education level, marital
status, information about whether the patient lived alone, employment status,
smoking status, and history of nicotine dependence were obtained during
semistructured interviews conducted in the interview room on the ward by
two psychiatrists (Y.U., I.M.) before discharge (median interval after
surgery, 13 days). Preoperative smoking status was based on patients
self-reports. Current smokers were defined as those who smoked at the
time of surgery or had quit smoking within the previous year, and
ex-smokers were defined as those who had quit smoking 1 or more years
before surgery. History of nicotine dependence was assessed according to
the DSM-III-R.26
Pathologic disease stage was obtained from the patients medical charts,
and PS, pain, and dyspnea were based on semistructured interviews conducted in the interview room of the Outpatient Service, Thoracic Oncology
Division, National Cancer Center Hospital East, by two psychiatrists (Y.U.,
I.M.) 1 month after surgery. The evaluation of PS was based on the Eastern
Cooperative Oncology Group criteria. Pain and dyspnea were graded on a
four-point verbal scale: (0) absent, (1) mild, (2) moderate, and (3) severe.
At 1, 3, and 12 months after surgery (median intervals after surgery, 31
days, 92 days, and 377 days, respectively), a semistructured interview was
conducted to obtain information on demographic and clinical characteristics
and was immediately followed by psychological measurements using the
SCID28 and the Profiles of Mood States (POMS) scale.39 A blood specimen
was collected at 12 months after surgery to determine smoking status
chemically.

Most measures at baseline, including measures of depression and the

POMS, could not be performed before surgery for NSCLC, mainly because we
judged that the baseline interview before surgery would be stressful to most
patients. They had only been informed by the hospital of the day they would be
admitted for surgical treatment of NSCLC 1 or 2 days in advance. Another
reason was the practical problem of not being able to interview patients because
of the brief interval between the time they were admitted and the operation
(usually 2 or 3 days). We therefore scheduled the baseline interview at 1 month
after surgery, by which time patients had been informed of the final pathologic
diagnosis.
When patients were diagnosed with depression, we recommended psychiatric consultation to the attending physician. When patients agreed, routine
psychiatric consultations were provided. Our study was, therefore, limited
because we were unable to observe the natural course of depression and
psychological distress during the year after curative resection.

Measures
At 1, 3, and 12 months after surgery, a psychiatrist (I.M.) used the SCID
during an interview to evaluate the patients for depression during the
previous month. Patients were also evaluated using the SCID for history of
depression. Whether depression was present before the patient was told of
the diagnosis of NSCLC and between when the patient was told of the
diagnosis and surgery was determined by patient report. The number of
major depressive episode items according to the DSM-III-R was obtained by
summing the number of the following nine items that were present at the
time: (1) depressive mood, (2) diminished interest or pleasure, (3) change in
body weight or appetite, (4) insomnia or hypersomnia, (5) psychomotor
agitation or retardation, (6) fatigue or loss of energy, (7) feelings of
worthlessness or guilt, (8) loss of concentration or indecisiveness, and (9)
suicidal thoughts. The diagnosis of depression was made according to the
criteria for major and/or minor depression. Major depression was diagnosed
when five or more items, including either depressive mood or diminished
interest or pleasure, were present; minor depression was diagnosed when two
to four items, including depressive mood or diminished interest or pleasure,
were present.
As expected, it was difficult to determine whether somatic symptoms, such
as appetite loss, insomnia, and fatigue, were attributable to depression or
surgical treatment. There are four approaches to diagnose depression of the
medically ill patient: to exclude somatic symptoms (exclusive); to substitute
psychological symptoms for somatic symptoms (substitutive); to count
somatic symptoms toward a depression diagnosis unless symptom is clearly
and fully accounted for by a general medical condition (etiologic); and to
include somatic symptoms (inclusive).40 Because the rater must make a
judgment about the cause of individual symptoms, the etiologic approach
may be less reliable than the exclusive, substitutive, and inclusive approach.
We elected to use an inclusive diagnostic approach (to prevent underdiagnosis of depression), which is considered to be the most important approach
in the clinical setting, although this approach may result in overestimation of
depression in the medically ill patient. The reliability of the interview ratings
was determined by having a second rater (Y.U.) attend a random sample
consisting of 30 interviews (4.8%). The interrater agreement (kappa) values
for the diagnosis of depression, major depression, and minor depression were
0.78, 1.00, and 0.65, respectively. Ratings for each of the nine individual
items were also reliable, with the kappa values ranging from 0.65 to 1.00.
Patients psychological distress was assessed using the POMS scale, a
65-item self-rating scale measuring six emotional states (tension-anxiety,
depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment), and its summary score, the total mood disturbance
(TMD) score.39 The validity and reliability of the Japanese version of the
POMS have been confirmed.41
Plasma cotinine concentrations were blindly determined in duplicate by a
high-performance liquid chromatography method with ultraviolet detection
according to the method described by Hariharan et al.42 The minimum
quantifiable concentration was 2 ng/mL. Patients with a cotinine concentration of less than 20 ng/mL were classified as nonsmokers, and patients with
concentration of 20 ng/mL were classified as smokers.

Statistical Analysis
Standard descriptive statistics were used to characterize the distributions
of the diagnosis of depression and the POMS scores at the 1-, 3-, and
12-month follow-up visits. Intergroup comparisons of categorical and non-

DEPRESSION AFTER LUNG CANCER SURGERY

parametric variables were performed using the 2 test and the Wilcoxon rank
sum test, respectively. Associations between continuous variables were
examined by calculating Spearman rank correlation coefficients. The
changes over time in the POMS scores were tested using the Wilcoxon test
or the Friedman test. The percentages of patients with depression were
compared across the two or three time points by the McNemar test or the
Cochran Q test.
The predictors examined were age, sex, education, marital status, whether
the patient lived alone, employment status, type of surgery, preoperative
%VC, preoperative %FEV1, preoperative PS, preoperative smoking status,
smoking status at 12 months after surgery, history of nicotine dependence,
history of depression before being told of the diagnosis of NSCLC, history
of depression between the diagnosis of NSCLC and surgery, and PS, pain,
dyspnea, depression, and POMS-TMD score at 1 month after surgery.
After the results for the correlations between biomedical and psychosocial
variables related to depression and the POMS-TMD score at 12 months after
surgery in the univariate comparisons (P .25) had been examined
carefully, they were entered into multivariate models to examine the
predictive factors of depression and the POMS-TMD score at 12 months
after surgery. A logistic regression analysis with backward elimination was
then used with alpha 0.05 as the significance criterion to select the final
models of depression, and multiple regression analysis with backward
elimination was performed to examine the predictors of the POMS-TMD
score at 12 months. In all statistical evaluations, P values of 0.05 or less were
considered indicative of significant differences. SPSS 10.0J for Windows
statistical software (SPSS Japan Institute Inc., Tokyo, Japan, 2000) was used
for all data analyses.

RESULTS

Curative resection was confirmed by the final pathologic

report of disease stage in 262 (86.5%) of the 303 NSCLC
patients who underwent standard surgery between June 1996 and
April 1999. At the time of the 1-month interview, three patients
could not be contacted and 20 refused to participate in the study
(10 of them because of the psychological burden, three because
of the psychological and physical burden, four because of the
physical burden, and three for unknown reasons). By the time of
the 3-month follow-up, two patients had been lost to follow-up,
two had died, and seven refused to participate (four because of
the psychological burden, one because of the physical burden,
one because of time constraints, and one for unknown reasons).
By the time of the 12-month follow-up, five patients had been
lost to follow-up, seven had died, three were too ill to participate,
and one refused to participate for unknown reasons. Thus, the
final study group consisted of 212 patients, representing 80.9%
of all eligible patients.
Data for the eligible patients who had undergone successful
surgical resection but did not participate in the study (n 50,
19.1%) were available in regard to age, sex, education, marital
status, preoperative PS, and clinical disease stage. More of the
nonparticipants were unmarried (26.1% of nonparticipants v
16.0% of participants, P .018), and significantly more nonparticipants had advanced clinical stage disease (stage IIIA:
30.0% of nonparticipants v 6.6% of participants, P 0.001), but
the two groups did not differ with respect to any other available
data. Of the 17 nonparticipants who refused to participate at the
time of the follow-up examinations for reasons that included
psychological burden, one was diagnosed with major depression
after referral to the Psychiatry Division. After psychiatric referral,
one of the 10 patients who could not be contacted was diagnosed
with major depression, and one of the three who were judged to be
too ill to participate was diagnosed with minor depression.
The mean age SD of the 212 cancer patients who participated in the study was 62.1 10.8 years (median, 63.5; range,

71
22 to 83), 39.6% were female, 84% were married, 7% lived
alone, and 33% had a junior high school education or less.
Smoking status was as follows: current smokers, 80 (37.7%);
ex-smokers, 54 (25.5%); and nonsmokers, 78 (36.8%). Of the
current and ex-smokers, 89 participants had a history of nicotine
dependence. Preoperative PS was grade 0 in 148 patients
(69.8%), grade 1 in 63 patients (29.7%), and grade 2 in one
patient (0.5%). Pathologic stage I disease was the most common
stage (n 165; 77.8%), followed by pathologic stage II (n 33,
15.6%), and pathologic stage IIIA (n 14; 6.6%). Lobectomy
was performed in 203 patients (95.8%) and pneumonectomy in
nine (4.3%). Preoperative respiratory function was generally
good: 19 patients (9.0%) had a %VC below 80%, and 44 (20.8%)
had a %FEV1 below 70%. According to the results of the serum
cotinine assay 1 year after surgery, 21 of the current smokers
(n 80) and none of the ex-smokers (n 54) had continued
to smoke.
Table 1 shows preoperative and 12-month postoperative
respiratory function in the form of %VC and %FEV1; preoperative, 1-, 3-, and 12-month scores on the PS scales; and
prevalence of depression and POMS scores at 1, 3, and 12
months postoperatively. The results show a statistically significant reduction in %VC (15%) at 1 year after surgery, but no
change in %FEV1. There were significant reductions in PS
scores after surgery; PS at 12 months returned to the preoperative level. Pain and dyspnea significantly decreased at 1, 3, and
12 months after surgery (pain, 2.50 0.66, 2.16 0.64, and
1.83 0.68, respectively, P .001; dyspnea, 2.30 0.68,
2.10 0.69, and 1.81 0.68, respectively, P .001).
The 1-month prevalence of depression at 1, 3, and 12 months
was 8.0%, 5.2%, and 4.7%, respectively, and none of the
differences in 1-month prevalence of depression during the year
were significant (Table 1). The 1-month prevalence of minor
depression at 1, 3, and 12 months was 3.3%, 2.4%, and 3.3%,
respectively, with no significant changes during the year. The
1-month prevalence of major depression at 1, 3, and 12 months
was 4.7%, 2.8%, and 1.4%, respectively, showing a tendency to
decrease, but none of the differences in 1-month prevalence of
depression during the year were significant.
The clinical course of the depression is shown in Fig 1. Only
three (17.6%) of the subjects with depression at 1 month (n
17) were diagnosed with depression at 12 months. Of the
subjects found not to be depressed at 1 month (n 195), seven
were diagnosed with depression at 12 months. The number of
patients with a history of depression before the diagnosis of lung
cancer was 30 (14.2%). The number of patients with a history of
depression after the diagnosis of lung cancer but before surgery
was 24 (11.3%).
Four of the 10 patients with major depression at 1 month and
none of the seven subjects with minor depression at 1 month
were referred to the Psychiatry Division by the attending
physician immediately after the 1-month interview. After psychiatric intervention, two of the four patients with major depression at 1 month were not diagnosed with depression at 3 months,
but the other two were still diagnosed with major depression and
under psychiatric treatment. At the 12-month follow-up, one
patient was still diagnosed with major depression, but the other
three were not diagnosed with depression. Only two of the five
patients with minor depression at 3 months were referred to the
Psychiatry Division, and neither patient was diagnosed with

72

UCHITOMI ET AL
Table 1.

Respiratory Function, Performance Status, Depression, and Psychological Distress in NonSmall-Cell Lung Cancer Patients After Curative
Resection (n 212)

Variable

%VC
%FEV1

Performance status (ECOG)

POMS-TMD
Tension-anxiety
Depression-dejection
Anger-hostility
Vigor-activity
Fatigue-inertia
Confusion-bewilderment

Depression
Major depression
Minor depression

Preoperative
Mean SD

12-Month*
Mean SD

104.5 16.6
75.2 9.4

89.1 15.7
75.0 11.6

.001
.124

Preoperative Mean
SD

1-Month Mean
SD

3-Month Mean
SD

12-Month Mean
SD

0.31 0.47

1.01 0.32
20.8 23.3
7.0 4.7
6.3 6.8
4.3 5.4
9.3 5.5
5.9 4.5
6.6 3.5

0.66 0.50
18.2 23.1
7.5 4.4
6.2 7.1
4.8 4.8
12.0 6.2
5.6 4.5
6.1 3.5

0.31 0.50
18.7 24.2
7.5 4.2
6.6 6.7
6.0 6.0
13.3 5.8
5.4 4.7
6.4 3.7

.001
.221
.028
.311
.001
.001
.227
.110

.001
.177
.063
.435
.001
.001
.121
.611

1 Month
n (%)

3 Month
n (%)

12 Month
n (%)

17 (8.0)
10 (4.7)
7 (3.3)

11 (5.2)
6 (2.8)
5 (2.4)

10 (4.7)
3 (1.4)
7 (3.3)

.203
.071
.801

.189
.065
.99

*For respiratory function at 12 months, n 190.

Across all months.
1-month versus 12-month comparison only.
For POMS at 1 and 3 months, n 210.
Abbreviations: ECOG, Eastern Cooperative Oncology Group; POMS-TMD, Profiles of Mood States-total mood disturbance.

depression at the 12-month follow-up. Of the six patients

referred to the Psychiatry Division, all received supportive
psychotherapy and/or antidepressant treatment, and five were not
diagnosed with depression at 12 months after surgery.
There was no change in the POMS-TMD score during the year
after surgery (Table 1). Of the six subscales of the POMS,
although the anger-hostility score had increased and the tensionanxiety score had increased slightly but significantly, the vigoractivity scale had also increased significantly. After the six
patients referred to the Psychiatry Division were excluded, the
POMS-TMD score did not change during the year after surgery
(POMS-TMD scores at 1, 3, and 12 months were 19.9 22.8,
17.9 22.8, and 18.5 23.9, respectively, P .281, n 202).
After the 22 patients given recommendations for psychiatric
consultation were excluded, the POMS-TMD score did not

change during the year after surgery (POMS-TMD scores at 1, 3,

and 12 months were 17.6 20.6, 15.2 19.8, and 16.8 22.7,
respectively, P .214, n 187).
The results of the univariate analysis are shown in Table 2,
and age, sex, education, marital status, preoperative PS, preoperative smoking status, history of depression before lung cancer,
depression at 1 month, and POMS-TMD at 1 month were entered
into the depression model. In addition, age, sex, type of surgery,
preoperative %FEV1, history of depression before lung cancer,
history of depression between the diagnosis of lung cancer and
surgery, dyspnea at 1 month, depression at 1 month, and POMSTMD at 1 month were entered into the POMS-TMD model.
The results of the multivariate analysis are shown in Table 3.
Depression and the POMS-TMD score at 1 month were significant predictors of the outcome at 12 months. History of

Fig 1. Clinical course of major and minor depression in nonsmall-cell lung cancer
patients during the 12 months after curative
resection (n 212).

73

DEPRESSION AFTER LUNG CANCER SURGERY

Table 2.

Demographic and Biomedical Characteristics, and Depression and Psychological Distress in NonSmall-Cell Lung Cancer Patients at 12
Months After Curative Resection: Univariate Analyses (n 212)
Depression
Characteristics

Age (years)
65
65
Sex
Male
Female
Education (years)
9
9
Married
No
Yes
Living alone
Yes
No
Employment
No
Yes
Type of surgery
Lobectomy
Pneumonectomy
Preoperative %VC
80
80
Preoperative %FEV1
70
70
Pathologic disease stage
I
II
IIIA
Preoperative performance status
0
1/2
Performance status at 1 month
0
1/2
Pain at 1 month
None to mild
Moderate to severe
Dyspnea at 1 month
None to mild
Moderate to severe
Preoperative smoking status
Current smoker
Ex- and nonsmoker
Smoking status at 12 months
Continued smoking
Others
Smoking status at 12 months
Quit smoking
Others
History of nicotine dependence
No
Yes
History of depression before lung cancer
No
Yes
History of depression between the
diagnosis of lung cancer and surgery
No
Yes
Depression at 1 month
No
Yes
POMS-TMD score at 1 month*
*For POMS at 1 month, n 210.
The mean value SD of depression yes (n 10).
The mean value SD of depression no (n 200).

POMS-TMD Score

n 10 (%)

120
92

8 (6.7)
2 (2.2)

.192

22.1 26.8
14.2 19.4

.057

128
84

4 (3.1)
6 (7.1)

.199

16.4 25.9
22.1 20.9

.010

71
141

8 (11.3)
2 (1.4)

.003

22.3 28.6
16.8 21.5

.499

34
178

3 (8.8)
7 (3.9)

.204

22.9 24.5
17.8 24.1

.252

15
197

1 (6.7)
9 (4.6)

.528

22.0 28.5
18.4 23.9

.770

114
98

6 (5.3)
4 (4.1)

.755

19.0 23.6
18.2 25.0

.588

203
9

10 (4.9)
0 (0)

.99

19.3 24.4
4.4 11.7

.042

19
193

0 (0)
10 (5.2)

.605

17.1 18.1
18.8 24.7

.938

44
168

2 (4.5)
8 (4.8)

.99

.186

165
33
14

7 (4.2)
2 (6.1)
1 (7.1)

.533

14.2 18.9
19.8 25.3
r 0.025
18.4 24.5
18.1 22.4
22.5 25.2

148
64

4 (2.7)
6 (9.4)

.070

17.3 21.7
21.8 29.1

.599

8
204

1 (12.5)
9 (4.4)

.325

8.8 22.9
19.0 24.2

.321

98
114

3 (3.1)
7 (6.1)

.346

18.2 24.7
19.0 23.8

.745

124
88

5 (4.0)
5 (5.7)

.744

17.6 25.2
20.2 22.6

.216

80
132

6 (7.5)
4 (3.0)

.183

21.8 29.1
16.7 20.5

.477

21
191

.259

24.3 30.0
18.0 23.5
24.3 30.0
20.9 29.1
17.8 22.0

.522

59
153

2 (9.5)
8 (4.2)
2 (9.5)
4 (6.8)
6 (3.9)

123
89

4 (3.3)
6 (6.7)

.327

16.3 20.0
21.9 28.8

.427

182
30

6 (3.3)
4 (13.3)

.037

17.1 24.0
28.1 23.1

.007

188
24

8 (4.3)
2 (8.3)

.315

16.8 22.8
33.2 30.0

.009

195
17

7 (3.6)
3 (17.6)
28.6 19.4
20.4 23.5

.036

16.7 22.5
40.6 31.7
r .592

.001

.470

.133

Mean SD

.718

.733

.001

74

UCHITOMI ET AL
Table 3.

Predictors of Depression and Psychological Distress of NonSmall-Cell Lung Cancer Patients at 12 Months After Curative Resection:
Logistic and Multiple Linear Regression Analysis

Dependent Variables/Independent Variables

Depression (n 212)
Depression at 1 month
Junior high school education or less

SE

OR

95% CI

2.08
2.35

0.83
0.84

7.98
10.50

1.58-40.39
2.04-54.10

.012
.005

POMS-TMD (n 210)
POMS-TMD at 1 month
History of depression between the diagnosis of
lung cancer and surgery

R2

SE

Standardized
Coefficient

.272
.241
.031

0.06
4.60

0.47
0.18

.001
.003

Abbreviation: POMS-TMD, Profiles of Mood Disturbance-total mood disturbance.

depression between the diagnosis of lung cancer and surgery was

also a significant predictor in the POMS model. Junior high
school education or less was a significant predictor in the
depression model.
After the six patients referred to the Psychiatry Division were
excluded, the same predictors continued to be significant in both
the depression model (depression at 1 month, odds ratio [OR]
8.14, P .030; 95% CI, 1.23 to 53.93, junior high school
education or less, OR 9.18, P .009, n 206, 95% CI, 1.73
to 48.74) and the POMS model (POMS-TMD at 1 month,
standardized coefficient 0.47, P .001; history of depression
after lung cancer before surgery, standardized coefficient 0.18,
P .003, n 204). After the 22 patients given recommendations for psychiatric consultation were excluded, junior high
school education or less did not remain a significant predictor in
the depression model (OR 5.13, , P .055, n 190, 95% CI,
0.97 to 27.19) but the POMS-TMD score at 1 month continued
to be a significant predictor in the POMS model (standardized
coefficient 0.53, P .001, n 188).
Because the predictors in both models included perioperative
depression, that is, a depression episode between the diagnosis of
lung cancer and surgery or at 1 month, the data were separated
according to whether the patients had experienced perioperative
depression and then reanalyzed (Table 4). Of the 37 patients with
perioperative depression (n 37), four had a depression episode
both times, that is, a depression episode between the diagnosis of
lung cancer and surgery and an episode 1 month after curative
resection. One of the predictors in the POMS model, the POMS

Table 4. Predictors of Psychological Distress at 12 Months After Curative

Resection of NonSmall-Cell Lung Cancer in Patients With and Without
Perioperative Depression: Multiple Linear Regression Analyses (n 210)
Dependent Variables/Independent Variables

Patients without perioperative depression

(n 174)
POMS-TMD
POMS-TMD at 1 month
Patients with perioperative depression
(n 36)
POMS-TMD
Junior high school education or less

Standardized
Coefficient

.251
.251 0.07

0.50

.001

.278
.278 10.10

0.53

.001

R2

SE

NOTE. Perioperative depression means a depression episode between the diagnosis of lung cancer and surgery or at 1 month after curative resection. Four patients
had a depression episode both between the diagnosis of lung cancer and surgery
and at 1 month.
Abbreviation: POMS-TMD, Profiles of Mood States-total mood disturbance.

score at 1 month, continued to predict in the model of subjects

without perioperative depression (Table 4A), but no significant
predictors remained in the depression model of subjects without
perioperative depression (junior high school education or less,
OR 4.87, P .063, n 175, 95% CI, 0.92 to 25.88). After
the 17 patients diagnosed with depression at 1 month were
excluded from the depression model, junior high school education or less showed a tendency to be a predictor (OR 5.21, P
.053, n 195, 95% CI, 0.98 to 27.59).
In the models of the subjects with perioperative depression
(Table 4B), junior high school education or less became a
significant predictor in the POMS-TMD model. No significant
predictors remained in the depression models of the subjects
with perioperative depression (n 37), although all three
subjects diagnosed with depression at 12 months had a junior
high school education or less.
DISCUSSION

This study is the first to prospectively assess depression and

psychological distress in NSCLC patients during a 1-year period
after curative resection and to identify predictors of their
psychological outcome at 12 months after surgery. Our study
was designed to obtain comprehensive data concerning depression by using a rigorous diagnostic method and reliable, valid,
self-administered instruments. However, most measurements at
baseline, including measures of depression and psychological
distress, could not be obtained before surgery for NSCLC,
thereby limiting the comparison of overall degree of change
from preoperative psychological functioning. Moreover, we
should indicate that recommendations for psychiatric consultation to the attending physicians in 22 cases at 1 or 3 months after
surgery and psychiatric interventions in six cases may have
affected the prevalence of depression and psychological distress.
The high attrition rate (19.1%) together with the fact that 17
(41.5%) of the 41 surviving nonparticipants refused to participate for reasons that included psychological burden mean that
the prevalence of depression and psychological distress at 3
months and 12 months may have been underestimated.
Despite several limitations, our finding showed that the
prevalence of depression did not significantly change during the
year after surgery (range, 4.7% to 8.0%). This finding appears to be
supported by the finding that the NSCLC patients psychological
distress measured by POMS-TMD did not change during the year
after surgery, even after the six patients referred to the Psychiatry
Division or the 22 patients given recommendations for psychiatric
consultation were excluded. Even though the prevalence of depres-

DEPRESSION AFTER LUNG CANCER SURGERY

sion was much lower than among lung cancer patients as a whole,
including patients with advanced and small-cell lung cancer
(15% to 44%),21-25 it was not low enough to be considered
negligible (0.9% to 3.7% in the general population).30-32
Although there have been no long-term studies of depression
after surgery for NSCLC, one study5 examined global QOL
according to the Quality of Life Index43 before and 1, 3, 6, and
9 months after surgery in 117 consecutive subjects who underwent thoracotomy for a certain or presumptive diagnosis of lung
cancer. Dales et al5 observed deterioration of QOL during the
first 3 months postoperatively in those with a final diagnosis of
cancer (n 91) and found that although their QOL rebounded to
its preoperative level, it did not reach the level of those in whom
the final diagnosis was not cancer (n 26). Our results are
similar to their findings in that QOL did not reach the level of
those without a final diagnosis of cancer during the 9 months
after surgery. Neither depression nor QOL of the NSCLC
patients after curative resection appears to decrease spontaneously. Depression should be assessed repeatedly and should not
be underrecognized even after curative resection. Because depression at 1 month was a significant predictor, easy selfadministered screening tools, such as the HADS,44,45 might be
beneficial to patients during the first year after successful
surgical treatment of NSCLC.
Another noteworthy finding in this study was that the prevalence of depression did not significantly decrease during the year
after surgery, even though only three (18%) of the 17 patients
with depression at 1 month after surgery were diagnosed with
depression at 12 months. Seven (70%) of the 10 patients with
depression at 12 months were diagnosed for the first time. In two
studies that prospectively assessed depression before and after
treatment for inoperable NSCLC,24, 25 the clinical course of the
depression could be explained in part by a transient reaction to
the diagnosis and treatment of cancer, by persistence of the
reaction over time, or by worsening of the PS and the development of pain and dyspnea. In contrast, the results of our study
showed a significant reduction of PS, pain, and dyspnea during
the year after surgical treatment of early NSCLC; these findings
are consistent with previous reports.5-7 One possible explanation
for the finding that in most of the patients diagnosed with
depression at 12 months it was diagnosed for the first time, is that
junior high school education or less was a significant predictor of
depression, although it became a marginal and not significant
predictor after subjects with depression at 1 month were excluded (P .053, n 195). The results of the study indicate that
medical professionals should pay careful attention to lesseducated NSCLC patients after curative resection.
There was no change in the NSCLC patients psychological
distress measured by POMS-TMD during the year after surgery,
although all six subscale scores of the NSCLC patients in this
study were below the mean scores of healthy Japanese populations 60 years of age or more on the Japanese version of the
POMS.41 Despite the significant reduction in PS to the preoperative level, both the anger-hostility and tension-anxiety score of
the POMS increased during the year after surgery; however,
there was a favorable change in the vigor-activity score. Because
a history of depression between the diagnosis of lung cancer and
surgery was a significant predictor, on the basis of the results of
our study as a whole, repetitive perioperative assessments of
depression as well as careful attention to less-educated patients

75
might lead to early detection of and early treatment for depression, resulting in amelioration of depression and psychological
distress during the year after curative resection of NSCLC.
Although it has been recommended that cancer patients be
routinely screened for distress,46 accumulating data indicate that
screening programs for depression consume considerable resources and are not an efficient means of improving the mental
health outcome of medical patients.47 If the sensitivity (91.5%)
and the specificity (65.4%) of the HADS used to screen for
depression in Japanese cancer patients45 were applied in this
study, the positive predictive value would be 25.3% for depression between the diagnosis of lung cancer and surgery and 19.3%
for depression at 1 month after surgery, and at least 2.5 and 2.4
patients/mo, respectively, would have to be interviewed by
medical professionals with knowledge of the diagnostic procedures for depression to make routine screening efficient enough
to be practical.
Being informed of a diagnosis of lung cancer could be
considered to be an acute stressful life event, as would a
diagnosis of any serious physical illness. According to the
severity of psychosocial stressors scale of the DSM-III-R,26
being diagnosed with a serious illness is graded as an extremely
severe psychosocial stressor, the same as the death of a spouse;
the grade is between a severe event (eg, divorce) and a
catastrophic event (eg, death of a child). Previous studies on the
death of a spouse have demonstrated a high prevalence of major
depression that decreased over time but remained higher than in
the controls (33% to 35% at 1 month after the loss, 23% to 25%
at 2 months, 16% to 17% at 13 months, respectively).48,49 The
prevalence of major depression in this study appears to be much
lower than following an extremely severe psychosocial stressor
such as the death of a spouse, and it shows a tendency to
decrease during the year after surgery.
There were several limitations to this study. First, there was
sampling bias, because the results were obtained from only one
institution, which was a teaching cancer center hospital. Second,
recommendations for psychiatric consultation were made to the
attending physicians. Moreover, there was a high attrition
ratemany nonparticipants refused to participate for reasons
that included psychological burden, and psychiatric intervention
occurred for six patients with depression. In fact, five of the six
patients referred to the Psychiatry Division were not diagnosed
with depression at 12 months after surgery. Therefore, the
prevalence of depression and psychological distress may have
been underestimated as a result. Thus, if the depression in these
five patients had persisted without psychiatric interventions, the
prevalence of depression, major depression, and minor depression at 3 and 12 months would have been as high as 6.1%, 3.8%,
and 2.4%, respectively, at 3 months, and 7.1%, 2.8%, and 4.2%,
respectively, at 12 months. Third, it was disappointing that most
measurements at baseline, including measures of depression and
psychological distress, could not be obtained before surgery for
NSCLC, thereby limiting the comparison of overall degree of
change from preoperative psychological functioning. The short
preoperative period results from a difference in our institutions
medical procedure. Preoperative psychological status in this
study may not really reflect baseline mental health because of the
high stress of the moment. Fourth, the prevalence of major
depression in Asian countries is generally lower than in western
countries, possibly because of cross-cultural differences (ie,

76

UCHITOMI ET AL

social stigma, cultural reluctance to endorse mental symptoms,

and low divorce rate).50-52 The interpretation of the results in this
study is cautious. Fifth, depression may have been overestimated
because we elected to use an inclusive diagnostic approach. This
approach includes somatic symptoms, regardless of whether the
rater judges that the symptom is caused by medical or psychological causes, prevents underdiagnosis of depression, and is
reliable because of the high interrater agreement.53 Because
other approaches do not offer a clear significant advantage in
measuring depression and the need for treatment,54 the inclusive
approach may be recommended with limitations in the clinical
oncology setting. Finally, although the simple four-point verbal
pain rating scale is the most widely used in the clinical context,
the fact that we did not use a pain rating scale with higher
sensitivity to change may have adversely affected the pain and
dyspnea assessments in this study.55
Depression is not routinely assessed even in patients with
unresectable NSCLC, although the majority of the previous
extensive research on QOL has addressed the need for psychosocial support for such patients. Furthermore, patients face
uncertainty and fear of recurrence after curative resection, even

though surgical treatment for early-stage NSCLC is generally

considered curative. This study revealed that the prevalence of
depression did not reach a negligible level and did not change
after curative resection for NSCLC. It also provided information
indicating that perioperative depression and less-educated status
were significant predictors of depression at 12 months after
surgery. Overall, the study indicates that the psychological status
of resectable NSCLC patients needs to be systematically addressed during their overall rehabilitation, including pain and
dyspnea management. In addition, this study identified an area
that is under studied in the literature regarding cancer survivorship, especially in the context of curative treatment. In the future,
a randomized trial of coordinated psychosocial interventions on
the basis of patient screening and treatment should be performed
with the aim of ameliorating depression and psychological
distress during the year after curative resection.
ACKNOWLEDGMENT
We are grateful to the patients and the physicians of the Thoracic
Oncology Division, National Cancer Center Hospital East, and for a
Grant-in-Aid for Cancer Research from the Japanese Ministry of Health and
Welfare.

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