Surgical resection of recurrent lung cancer in patients following curative resection.

Abstract

We reviewed our experience with resection of recurrent lung cancer to evaluate the benefit and risk of the procedure. From December 1994 to December 2003, 29 consecutive patients underwent pulmonary resections for recurrent lung cancer. The mean duration from the first resection to second surgery was 25.4+/-15.1 months for the definite 2nd primary lung cancer (n=20) and 8.9+/-5.7 months for metastatic lung cancer (n=9). The procedures at the second operations were completion-pneumonectomy in 11 patients, lobectomy in 5 patients, wedge resection in 12 patients and resection and anastomosis of trachea in 1 patient. Morbidity was observed in 6 (21%) of the patients and the in-hospital mortality was two patients (7%) after the repeated lung resection. Tumor recurrence after reoperation was observed in 14 patients (48%). The actuarial 5-yr survival rate was 69% and the 5-yr disease free rate following reoperation was 44%. No significant difference was found in overall survival and disease free survival between the 2nd primary lung cancer group and the metastatic lung cancer group. The recurrence rate following reoperation was significantly different between the wedge resection group and lobectomy/completion pneumonectomy group (p=0.008), but the survival rate was not significantly different (p=0.41). Surgical intervention for recurrent lung cancers can be performed with acceptable mortality and morbidity. If tolerable, completion pneumonectomy or lobectomy is recommended for resection of recurrent lung cancer.

Full text

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INTRODUCTION
The recurrence of lung cancer after complete resection gen-
erally results in a poor prognostic situation with less than one
year of life expectancy. When a single lung nodule is detect-
ed during follow-up, it is usually one of the manifestations of
the systemic metastasis. However, one distinct feature is a sec-
ond primary metachronous lung cancer appearing after the
initial treatment of the primary lung cancer. Although there
are criteria that can be applied in this situation, it is some-
times very difficult in clinical practice to distinguish between
a new lung cancer and a metastatic one. Therefore, some re-
searchers have insisted an aggressive surgical approach, when-
ever possible, as the survival rate after surgery is quite good
(1-7). On the other hand, many doubts have been expressed
concerning the utility of repeated surgery for recurrent lung
cancer, as it is associated with a poor overall survival (8, 9).
We are convinced of the value of the aggressive surgical
approach for all the cases whose the functional condition
makes resection possible. The aim of this study is to report
the result of re-resection for recurrent lung cancer while focus-
ingon the rationale for this aggressive surgical approach.
MATERIALS AND METHODS
There were 1,461 patients who underwent operations for
primary lung cancer from December 1994 to December 2003.
The operations were performed by a group of three thoracic
surgeons in a single hospital. Every patient was followed-up
by the same surgeons on a regular follow-up schedule (every
3-4 months for 2 yr, every 6 months for the next 3 yr and then
every year). A chest CT was performed at every visit. When
recurrent disease in the lung was suspected, repeated CT scan
were performed at 2 months intervals, and positron emission
tomography (PET), bronchoscopy and/or percutaneous nee-
dle aspiration (PCNA) were also performed. There were 29
consecutive patients who underwent repeated surgical resec-
tions for recurrent lung cancer after curative resection for lung
cancer. At the time of initial operation, histology and patho-
logical staging are shown in Table 1. The diagnostic methods
of recurrent lung cancer were chest CT in 11 patients, PET
in 9 patients, PCNA in 6 patients, and bronchoscopic biop-
sy in 3 patients. The second primary lung cancers were de-
fined using the criteria outlined by Martini and Melamed
(10). A neoplasm was defined as a metastatic lung cancer if
Hyoung Soo Kim*, Hoseok I,
Yong Soo Choi, Kwhanmien Kim,
Young Mog Shim, Jhingook Kim
Department of Thoracic and Cardiovascular Surgery,
Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul; Department of Thoracic
and Cardiovascular Surgery*, Hallym University
Medical Center, Seoul, Korea
Address for correspondence
Jhingook Kim, M.D.
Department of Thoracic and Cardiovascular Surgery,
Samsung Medical Center, Sungkyunkwan University
School of Medicine, 50 Ilwon-dong, Gangnam-gu,
Seoul 135-230, Korea
Tel : +82.2-3410-3483, Fax : +82.2-3410-0089
E-mail : jkim@smc.samsung.co.kr
*Poster presented at the 10th World Conference on
Lung Cancer-IASLC, Vancouver, Canada, AUG 10-14,
2003.
224
J Korean Med Sci 2006; 21: 224-8
ISSN 1011-8934
Copyright � The Korean Academy
of Medical Sciences
Surgical Resection of Recurrent Lung Cancer in Patients Following
Curative Resection
We reviewed our experience with resection of recurrent lung cancer to evaluate
the benefit and risk of the procedure. From December 1994 to December 2003, 29
consecutive patients underwent pulmonary resections for recurrent lung cancer. The
mean duration from the first resection to second surgery was 25.4±15.1 months
for the definite 2nd primary lung cancer (n=20) and 8.9±5.7 months for metastatic
lung cancer (n=9). The procedures at the second operations were completion-pneu-
monectomy in 11 patients, lobectomy in 5 patients, wedge resection in 12 patients
and resection and anastomosis of trachea in 1 patient. Morbidity was observed in
6 (21%) of the patients and the in-hospital mortality was two patients (7%) after the
repeated lung resection. Tumor recurrence after reoperation was observed in 14
patients (48%). The actuarial 5-yr survival rate was 69% and the 5-yr disease free
rate following reoperation was 44%. No significant difference was found in overall
survival and disease free survival between the 2nd primary lung cancer group and
the metastatic lung cancer group. The recurrence rate following reoperation was
significantly different between the wedge resection group and lobectomy/comple-
tion pneumonectomy group (p=0.008), but the survival rate was not significantly dif-
ferent (p=0.41). Surgical intervention for recurrent lung cancers can be performed
with acceptable mortality and morbidity. If tolerable, completion pneumonectomy
or lobectomy is recommended for resection of recurrent lung cancer.
Key Words : Lung Neoplasms; Surgical Procedures, Operative; Neoplasm Recurrence, Local
Received : 10 August 2005
Accepted : 24 October 2005

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Resection of Recurrent Lung Cancer Following Curative Resection
225
it was a same histology occurring in the same anatomic site
within 2 yr after first operation. A second primary cancer was
a tumor of different histology, or if histology was the same,
the disease free interval of recurrent cancers was at least 2 yr
or the second cancer was in different lobe or lung, or origin
from carcinoma in situ in the absence of other extrapulmonary
or common lymphatic metasitasis. On the repeated lung oper-
ations, mediastinoscopy was not performed because most of
the patients already had had mediastinoscopy performed at
the first lung resection. However, careful intraoperative nodal
staging was performed by dissecting the intrapulmonary, hilar
and ipsilateral mediastinal nodes. Although the extent of re-
section of recurrent lung cancer in early period was dependent
on the surgeon’s preference, thereafter we have made an attem-
pt to avoid limited resection if patients had predictive post-
operative FEV1of more than 1.0 L and acceptable cardiac func-
tion. Postoperatively, the same follow-up plan was applied
as for the first lung operation.
We analyzed included types of operation, the time between
two surgical interventions, operative findings and histology,
operative and post-operative complications and the hospital
Table 1. The patient characteristics
mortality as well as late death. The descriptive statistics are
summarized as the median or mean for the continuous vari-
ables and as frequencies and percentages for the categorical
variables. Survival and the disease free rate were analyzed by
the Kaplan-Meier and log-rank methods on SPSS for Window,
release 10.0 (SPSS Inc., Chicago, IL, U.S.A.). All differences
were considered significant at a p value less than 0.05.
RESULTS
29 consecutive patients underwent surgical resections for
recurrent lung cancer after curative resection for lung cancer.
The second primary lung cancer, by definition, was found in
20 cases. The remainder 9 cases were metastatic lung cancers.
The median age of patients was 61 yr (range, 45 to 75 yr) and
the male/female (22/7) ratio was 3.1:1. The smoking history
was observed in 16 patients (55%). The second primary tumor
was discovered on the same side as the first tumor in 19 pa-
tients. One had a histologically different tumor.
The mean time interval between the first operation and the
second operation was 20.3±15 months (Table 1). The mean
time interval between the first resection and the second resec-
tion was 25.4±15.1 months for the second primary lung
cancers and 8.9±5.7 months for the metastatic lung cancer.
The mean interval between the second operation and the sec-
ondrecurrence was 12.5±10.2 months.
The second operations were completion pneumonectomy
in 11 patients, lobectomy in 5 patients, wedge resection in
12 patients, and resection and anastomosis of the trachea in
1 patient (Table 2). The patient of tracheal resection was re-
curred at right lower paratracheal lymph node. Three patients
received adjuvant chemotherapy and one patient received radi-
ation therapy. The operative mortality rate was 6.8%. The
causes of death were pulmonary embolism in one patient and
respiratory failure in the other patient. Major morbidity was
observed in 6 (21%) patients after the repeated lung resection;
bronchopleural fistula was noted in 3 patients, myocardial
infarction and cerebral vascular accident were noted in 1 pa-
tient, pulmonary artery embolism occurred in 1 patient and
respiratory failure occurred in 1 patient. Tumor recurrence
after reoperation was observed in 14 patients (48%). In four
BAC, bronchoalveolar carcinoma; ca., carcinoma.
Age (median) (yr)61 (range 45-75)
Gender
Male:Female
Smoking (yes)
Histology
Squamous cell ca
Adenocarcinoma
BAC
Large cell ca
Epithelial-myoepithelial ca.
p-Stage (first resection)
IA
IB
IIA
IIB
IIIA
IIIB
IV
Operations (first resection)
Lobectomy
Bilobectomy
Sleeve lobectomy
Pneumonectomy
Diagnostic tools
PET
Chest CT
PCNA
Bronchoscopic biopsy
Mean interval from first resection
<12 months
12-24 months
24-36 months
36-48 months
<48 months
22:7
16 (55%)
13 (44.8%)
9 (31.0%)
5 (17.2%)
1 (3.4%)
1 (3.4%)
4 (13.8%)
12 (41.4%)
1 (3.4%)
6 (20.7%)
4 (13.8%)
1 ( 3.4%)
1 ( 3.4%)
17 (58.6%)
4 (13.7%)
6 (20.7%)
2 (6.8%)
9 (31.0%)
11 (37.9%)
6 (20.7%)
3 (10.2%)
20.3±15 month
9 (31.0%)
12 (41.3%)
2 ( 6.8%)
3 (10.2%)
4 (13.8%)
c-pneumonectomy, completion pneumonectomy; R & A, resection and
anastomosis.
2nd primary Metastatic Totalp value
2nd op. (2nd recurrence)
Wedge
Lobectomy
c-Pneumonectomy
R & A of trachea
2nd recurrence
10 (8)
5 (2)
4 (1)
1 (1)
12
2 (1) 12
5
11
1
14
0.03
7 (1)
20.06
Table 2.The 2nd operation and 2nd recurrence of recurrent lung
cancer

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226
H.S. Kim, H. I, Y.S. Choi, et al.
of these 14 patients, we performed the third operation; a com-
pletion pneumonectomy in 1 patient, wedge resection in 2
patients and multiple rib resection and chest wall reconstruc-
tion in 1 patient. The remaining ten patients were referred
for radiation therapy, chemotherapy or supportive care only
(Table 4).
Overall follow-up after reoperation ranged from 3 to 103
months with a mean of 41.4±22.3 months. The overall actu-
arial5-yr survival rate was 69% and the 5-yr disease free rate
following reoperation was 44% (n=29). No significant differ-
ence was detected in survival and the disease free rate between
the second primary lung cancer patients and the metastatic
lung cancer patients (Table 3, Fig. 1, 2). The disease free rate
following reoperation was significantly different between the
wedge resection group and anatomically curative resections
such as lobectomy/completion pneumonectomy group (p=
0.008), but the survival rate was not significantly different
(Fig. 3).
DISCUSSION
Recent improvements of such diagnostic tools as high-res-
olutionCT scan or PET scan allow physicians to detect recur-
rentlung cancer much earlier than before. However, there is
not yet a consensus for the postoperative follow-up strategy
of patients after complete resection for NSCLC. Westeel et al.
(11) and Angeletti et al. (1) reported that intensive follow-up
may improve patient survival by detecting recurrences at an
asymptomatic stage after surgery for NSCLC. It has been re-
ported that for detecting residual or recurrent NSCLC, PET
had a sensitivity of 100% and a specificity of 61.5-92%, but
chest CT only had a sensitivity of 67% and a specificity of
85% for the detection of tumor recurrence (12). In our study,
when the lesion was centrally located and the percutaneous
needle aspiration was difficult to perform, PET was then used
as a very effective diagnostic method. In our series, the diag-
nostic methods of recurrent lung cancer were chest CT in 11
patients, PET in 9 patients, PCNA in 6 patients, and bron-
1.2
No.
1st operationStage (first op.) Recur siteHistology
1
2
3
4
5
6
7
8
9
LLL
RLL
s-RUL
LP
RLL
s-RUL
LLL
LUL
RML
RUL
RML+RLL
LLL
RLL
LLL
Adenocarcinoma
Squamous
Large cell ca.
Squamous
Adenocarcinoma
Adenocarcinoma
Adenocarcinoma
Adenocarcinoma
BAC
BAC
Squamous
Adenocarcinoma
Adenocarcinoma
Epi.-myoepithelial ca.
IB
IA
IB
IIIA
IIIA
IIB
IB
IB
IA
IB
IIA
IIB
IA
IB
W-RUL
s-LUL
W-RML
W-RLL
W-LUL
W-LUL, LLL
W-LUL
W-LLL
W-RUL
W-RLL
R & A
RML
c-RP
c-LP
17
8
4.3
2.9
16.5
7
1.7
17.9
7.7
16.2
5.1
8
24.3
39.3
Brain
LLL
Pleura, bone
Brain
Brain
Multiple lung
Peritoneum
LLL
RUL
RML, RLL
Multiple pleura
Multiple lung
Multiple lung
Chest wall
RT
RT
RT
RT
Chemotherapy
W-LLL
W-RUL
c-RP
Chemotherapy
Chemotherapy
Chemothreapy
Op.
10
11
12
13
14
Table 4. The second recurrent lung cancer
s-RUL, sleeve right upper lobectomy; RML, right middle lobectomy; RLL, right lower lobectomy; LUL, left upper lobectomy; LLL, left lower lobectomy;
LP, left pneumonectomy; W-, wedge resection; R & A, resection and anastomosis of trachea; c-RP, completion right pneumonectomy; c-LP, comple-
tion left pneumonectomy; RT, radiation therapy; Op., multiple ribs resection and chest wall reconstruction.
2nd operationTime between 2nd
op. and 2nd recur
Treatment
Cumulative survival rate
1.0
0.8
0.6
0.4
0 12243648
FU (months)
60 7284 96 108 120
Fig. 1. Actuarial survival for recurrent lung cancer with 2nd primary
and metastatic tumor after the second operations.
Metastatic (n=9)
p>0.05
2nd primary (n=20)
Op, operatrion; ds, disease.
2nd primaryMetastatic Totalp-value
Mean survival
time after 2nd op.
(5-yr survival rate)
Mean ds free
time after 2nd op.
(5-yr ds free rate)
62.4±6.6
(69%)
78.5±14.7
(70%)
77.1±7.7
(69%)
0.92
37.1±7.9
(35%)
72.3±16.3
(69%)
52.7±9.1
(44%)
0.15
Table 3. Mean survival time and mean disease free time of recur-
rent lung cancer

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Resection of Recurrent Lung Cancer Following Curative Resection
227
choscopicbiopsy in 3 patients. When the recurrent lung can-
cerwas difficult to diagnose with using chest CT or PET, we
then performed invasive diagnostic methods. The initiation
of earlier therapy with the early detection of recurrences may
have improved the outcome compared with the therapy given
when the patient becomes symptomatic from the tumor (1,
3, 4, 6). Major complications occurred in 24% of our patients
after the second resections, which is comparable to the pre-
viously reported results of pulmonary resection for recurrent
lung cancers (3, 4, 17).
Martini and Melamed (10) in 1975 outlined the criteria for
differentiation between a second primary lung cancer and a
metastatic or recurrent lung cancer. Some reports have sug-
gested that patients with a second primary lung cancer have
a more favorable prognosis than patients with locally recur-
rent or metastatic disease (13-15). However, other reports did
not reveal a significantly different survival between patients
operated on for a second primary lung cancer or those patients
operated on for locally recurrent or metastatic disease (4, 5,
8, 9). Our data showed that the 5-yr survival rates were not
different between second primary lung cancer and the possi-
ble second primary or metastatic lung cancer. Yet the 5-yr
disease free rates for lobectomy/completion pneumonectomy
group were better than for wedge resection group. It may be
explained by the fact that the second operations had been
wedge resections for eight patients of the second primary lung
cancer subgroup (n=12) who had suffered a second tumor
recurrence. The Lung Cancer Study Group (16) reported that
a resection that is less extensive than lobectomy for primary
lung cancer places the patient at an increased risk of local
recurrence and this decreases the chances of long term survival.
The limited resections used in second primary lung cancer
group might have resulted in an increased risk for locoregional
recurrence, but the extents of the resection of recurrent lung
cancer did not influence the survival in another study (6, 17).
Donington et al. (7) reported that pulmonary resection of
bronchogenic carcinoma after pneumonectomy was associat-
ed with acceptable morbidity and mortality. Wedge resection,
when feasible, is the treatment of choice.
Voltolini et al. (4) has reported on the type of surgical treat-
ment used in case of metachronous second primary lung tu-
mor. The wedge resection was a reasonable and safe alterna-
tive to the standard resections in the elderly patients or in
those patients with a poor respiratory reserve and after a pneu-
monectomy. If the tumor was not in the periphery and if it
was less than 2 cm in diameter, they consider lobectomy as
the treatment of choice even for the second resection. The re-
currence rate was lower in the lobectomy/completion pneu-
monectomy group than in the wedge resection group.
The mean disease free time for lobectomy/completion pneu-
monectomy patients was longer than for the wedge resection
patients. Eight patients, who had undergone wedge resection
of second primary lung cancer, were proven to show recur-
rence. Therefore, lobectomy or completion pneumonectomy
is preferred to wedge resection as an operation for a second
primary lung cancer.
Surgical intervention for recurrent lung cancers can be per-
formedwith an acceptable mortality and morbidity. If it is tol-
erable, completion pneumonectomy or lobectomy are recom-
mendedprocedures of choice for recurrent lung cancer.
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