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1130-0108/2015/107/539-546Revista española de enfeRmedades digestivasCopyRight © 2015 aRán ediCiones, s. l.
Rev esp enfeRm dig (MadridVol. 107, N.º 9, pp. 539-546, 2015
ORIGINAL PAPERS
Characteristics and pattern of recurrence after curative surgery in oesophageal cancerElena Rodríguez-Camacho, Salvador Pita-Fernández, Sonia Pértega-Díaz, Beatriz López-Calviño and Teresa Seoane-Pillado
Clinical Epidemiology and Biostatistics Research Group. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña. A Coruña, Spain
ABSTRACT
Background and aim: Recurrence in oesophageal cancer continues to remain high after curative surgery. The aim of this study was to determine the presence of recurrence after curative surgery during follow-up, and the associated variables.
Methods: A retrospective and prospective follow-up study in patients with an anatomical-pathological diagnosis of oesophageal cancer who underwent curative surgery (n = 57) in the health district of A Coruña (Spain) during the period 2003-2008. The calculation of recurrence-free survival was made using a competing risks survival analysis.
Results: Out of the 57 patients included in the study, 87.7% were men with a mean age of 61.4 ± 10.3 years. The median follow-up period was 18.5 months, during which 28 recurrences were detected (50.9%). Patients with dysphagia on diagnosis of the disease, as well as patients in stages III-IV, have a higher probability of recurrence during the follow-up period. The median disease-free interval was 8.5 months. After one year of follow up, 57.1% of the recurrences were diagnosed and 82.1% after 2 years of follow-up. The median post-recurrence survival rate was 4.7 months. After adjusting for a multivariate regression model, the variable with an independent effect for predicting recurrence is the TNM classification (HR = 8.49).
Conclusions: The majority of the recurrences will be developed during the 2 years after surgery, with a very poor prognosis. The predictor variable for recurrence is the TMN classification.
Key words: Oesophageal neoplasms. Recurrence. Oesophagectomy. Survival. Follow-up studies.
INTRODUCTION
Oesophagus cancer is the eighth most common cancer at worldwide level, and is the sixth main cause of death from cancer (1). Surgery involving oesophagectomy is still the main therapeutic option (2,3), although even after receiving curative treatment the possibility of recurrence
in patients, either locoregional or distant, is still high, with percentages varying between 29% and 59% (4-16).
Different factors affect the risk of recurrence, mainly the location of the tumour, the local stage of the tumour, the degree of cellular differentiation and the presence of metastasis on diagnosis (5-9,11,12,14,16). It is important to understand the factors that favour the presence of tumour recurrence, as well as the different patterns of recurrence, in order to be able to design suitable therapeutic strategies for these patients.
The aim of this study was to demonstrate the charac-teristics and progress of patients with oesophageal can-cer who have undergone curative surgery, as well as to study the risk factors for developing a recurrence. Also, in patients with tumour recurrence, to analyse the different patterns of recurrence, their therapeutic management and their evolution.
MATERIALS AND METHODS
Study population
A total of 180 patients were diagnosed with anatomical-patho-logical confirmation of cancer of the oesophagus (CIE 9ª: 150) at the University Hospital Complex in A Coruña (Spain) from 1 Janu-ary 2003 to 31 December 2008. This study included all patients in the cohort (57 patients) who had undergone curative surgery, which enabled complete removal of the tumour along with the metastatic lymph nodes. A retrospective review of the patients’ clinical records was carried out together with a prospective follow-up until 31 Jan-uary 2012, in order to guarantee a minimum follow-up period of 3 years. The study excluded prevalent or recurring cases, multiple cancers, metastatic cancers, or those that had been treated and/or diagnosed at other hospitals.
Rodríguez-Camacho E, Pita-Fernández S, Pértega-Díaz S, López-Calviño B, Seoane-Pillado T. Characteristics and pattern of recurrence after curative surgery in oesophageal cancer. Rev Esp Enferm Dig 2015;107:539-546.
Received: 26-02-2015Accepted: 03-05-2015
Correspondence: Elena Rodríguez-Camacho. Clinical Epidemiology and Biostatistics Unit. Complexo Hospitalario Universitario de A Coruña. Xer-encia de Xestión Integrada de A Coruña. C/ Xubias de Arriba, 84. 15006 A Coruña, Spaine-mail: [email protected]
540 E. RODRÍGUEZ-CAMACHO ET AL. Rev esp enfeRm Dig (maDRiD)
Rev esp enfeRm Dig 2015; 107 (9): 539-546
Measurements
A study was made of the socio-demographic variables of the patient, their personal backgrounds, comorbidity variables using Charlson’s comorbidity index, the symptoms present at diagnosis, location of the tumour, histopathological cell type and tumour stage (TNM, seventh edition) (17,18). As data on risk factors and symp-toms were collected retrospectively from clinical records, we regis-tered it if it was indicated in the clinical records, although we were unable to quantify the frequency and amount of cigarette or alcohol consumption, nor the number of kilograms lost.
An analysis was made of the treatment received, surgery, chemo-therapy and radiotherapy.
Tumour recurrence was considered as the detection during the post-surgical follow-up period of reappearance of the neoplastic dis-ease either locoregional, distant, or both. Locoregional recurrence was defined as a recurrence isolated to the area of the anastomosis (perianastomotic) or in lymph nodes in the mediastinum and upper abdomen (supraceliac). Distant recurrence was defined as any spread of disease beyond a locoregional recurrence. The recurrence-free interval was defined as the time from the curative surgery to the first recurrence (locoregional, distant or both).
For all dead patients, cause of death was obtained from the Gali-cian Mortality Registry (General Directory of Public Health, Xunta de Galicia, Spain), according to the 21 diagnostic categories of the 10th revision of the International Classification of Diseases (ICD-10).
Sample size justification
The study included a total of 57 patients. This sample size makes it possible to detect as significant a Hazard Ratio of 2.85 or more with a prevalence of exposure of 50% and a censored data percent-age of 50% (confidence: 95%; Statistical power: 80%).
Statistical analysis
A descriptive study was made of the variables that were obtained. The global survival rate was calculated using the Kaplan-Meier methodology and recurrence-free survival using competing risks survival analysis. Proportional hazard assump-tion was assessed graphically by visual judgement of the log-mi-nus-log survival plots, as well as checking the significance of a time-dependent variable added to the regression model (by means of an interaction of survival time and each individual covariate) for quantitative covariates. The accumulated occurrence of tumour recurrence during the follow-up period was estimated, considering non-recurrence mortality as a competitive event, using the method proposed by Kalbfleisch and Prentice (19). The accumulated occur-rence of tumour recurrence according to different characteristics was compared using the test proposed by Gray (20). Finally, in order to identify which characteristics were associated with the risk of tumour recurrence, a multivariate analysis was carried out using the model proposed by Fine and Gray (21). All of the tests were carried out bilaterally, considering values of p < 0.05 as significant. The analyses were carried out using the programmes Epidat 3.1, SPSS 19.0 and R 2.15.1.
Ethics
The study was carried out according to the principles laid down in the Declaration of Helsinki and ensuring compliance with Spanish Law 29/2009, which “Regulates the use of and access to electron-ic medical records. Confidentiality was maintained in accordance with the current Spanish Data Protection Law (15/1999). The study received written approval from the regional Ethics Committee for Clinical Research (code 2011/372 CEIC Galicia).
RESULTS
Characteristics of the patients studied
Out of the 57 patients included in the study, 87.7% were male. The mean age of the patients was 61.4 ± 10.3 years, and the mean Body Mass Index (BMI) was 25.2 ± 3.9 kg/m2. Twenty-two patients (38.6%) had a background of gastro-oesophageal reflux, 80.7% were smokers, 57.9% were alcohol drinkers, and 49.1% had both risk factors. The score on Charlson’s comorbidity index age-adjusted was 2.7 ± 1.7, with 50.9% of the patients in a high comor-bidity range (≥ 3 points).
Forty-six patients (82.1%) presented with dysphagia at the time of diagnosis. A lower thoracic localisation (> 30-40 cm from the incisors) was the most frequent, in 49.1% of the cases. In the case of the tumours, 40 (70.2%) corresponded to squamous cell carcinomas, and 17 (29.8%) to adenocarcinomas. Thirty-seven patients (72.6%) were at stage II-III at the time of diagnosis, and five patients (9.8%) had metastatic lymph nodes (stage IV). Thirty-four patients (59.6%) received only surgical treatment, while 40.4% received surgical and oncological treatment (chemothera-py and/or radiotherapy). In those cases, chemotherapy and radiotherapy were mainly applied for neoadjuvant purposes (76.5% and 69.6% respectively) (Table I).
Progress of patients and likelihood of recurrence
The median follow-up period for the 57 patients who under-went curative surgery was 18.5 months (range: 0.3-92.4), with an overall chance of survival of 82.5% after six months, 59.2% after one year, and 23.1% after 5 years of follow-up.
During the follow-up, 28 (50.9%) patients were detect-ed with recurrence. Figure 1 shows the different progress options following curative surgery, together with the prob-ability of each of them in the different follow-up periods. In those patients who underwent curative surgery, the probability of being diagnosed with a tumour recurrence (locoregional tumour recurrence, distant recurrence or both) during the first year after surgery was 29.1%, while 25.5% of the patients died without presenting any recur-rence. Therefore, 45.4% of the patients who underwent curative surgery were alive and remained disease-free
Vol. 107, N.º 9, 2015 CHARACTERISTICS AND PATTERN OF RECURRENCE AFTER CURATIVE SURGERY IN OESOPHAGEAL CANCER 541
Rev esp enfeRm Dig 2015; 107 (9): 539-546
Table I. Baseline characteristics of the patients studied
na Mean SDb Median IQRc 95% CId (mean)
Age (years) 57 61.4 10.3 61.0 30.0-79.0 58.7-64.1
BMIe 41 25.2 3.9 24.8 18.2-32.8 23.9-26.4
Charlson’s comorbidity index 57 1.0 1.3 1.0 0.0-6.0 0.7-1.3
Charlson’s comorbidity index age adjusted 57 2.7 1.7 3.0 0.0-8.0 2.3-3.2
na % 95% CId (Mean)
Gender
Male
Female
50
7
87.7
12.3
78.3-97.1
2.9-21.7
Charlson’s comorbidity index age adjusted
No comorbidity (0-1 points)
Low comorbidity (2 points)
High comorbidity (≥ 3 points)
13
15
29
22.8
26.3
50.9
11.0-34.6
14.0-38.6
37.0-64.7
Gastro-oesophageal reflux*
Yes
No
22
35
38.6
61.4
25.1-52.1
47.9-74.9
Smoking
Yes
No
46
11
80.7
19.3
69.6-91.8
8.2-30.4
Alcohol consumption
Yes
No
33
24
57.9
42.1
44.2-71.6
28.4-55.8
Smoking and alcohol consumption
Yes
No
28
29
49.1
50.9
35.3-63.0
37.0-64.7
Dysphagia*
Yes
No
46
10
82.1
17.9
71.2-93.1
6.9-28.8
Tumour location
Cervical
Upper thoracic
Middle thoracic
Lower thoracic
Distal oesophagus
1
5
16
28
7
1.8
8.8
28.1
49.1
12.3
0.0-9.4
2.9-19.3
15.5-40.6
35.3-63.0
2.9-21.7
Histopathologic cell type
Squamous-cell carcinoma
Adenocarcinoma
40
17
70.2
29.8
57.4-82.9
17.1-42.6
TNM classification
Stage 0
Stage I
Stage II
Stage III
Stage IV
3
6
18
19
5
5.9
11.8
35.3
37.3
9.8
1.2-16.2
1.9-21.6
21.2-49.4
23.0-51.5
3.3-21.4
Treatment
Surgery
Surgery and chemotherapy and/or radiotherapy
34
23
59.6
40.4
46.0-73.3
26.7-54.0
na: Number of patients; SDb: Standard deviation; IQRc: Inter-quartile range; CId: Confidence interval; BMIe: Body mass index; *Symptoms/signs before oesophageal cancer diagnosis.
542 E. RODRÍGUEZ-CAMACHO ET AL. Rev esp enfeRm Dig (maDRiD)
Rev esp enfeRm Dig 2015; 107 (9): 539-546
Fig. 1. Recurrence probability for patients with oesophageal cancer after curative surgery.
one year after the surgery. Similarly, the probability of tumour recurrence five years after the surgery is 52.4%, while 29.6% of the patients have died without presenting any recurrence. Therefore, only 18% of the patients will be alive and disease-free five years after curative surgery.
Risk factors for recurrence
The risk factors for recurrence analysed are shown in table I. In the univariate analysis, the histopathologic cell type was not significantly associated with the probability of recurrence during the follow-up, nor any other variable studied, although it may be seen that patients with dyspha-gia on diagnosis, as well as patients in stages III-IV, had a higher probability of recurrence during the follow-up peri-od, as shown in figure 2. After carrying out a multivariate regression analysis, adjusting for gender, age, BMI, Crude Charlson’s comorbidity index, smoking and alcohol con-sumption, histophathologic cell type, TNM classification and treatment, it was found that the TNM classification
is associated with the presence of recurrence during fol-low-up in a statistically significant way (Table II). In order to adjust for age as a clinically relevant and confounding variable and avoid over-adjustment, we included in the model the Crude Charlson’s comorbidity index.
Disease-free survival and recurrence pattern
In patients with recurrence (n = 28), the median for the disease-free interval was 8.5 months (range: 2.0-56.0). After one year of follow-up, 57.1% of the recurrences were diagnosed and 82.1% after 2 years of follow-up, detecting the last recurrence in our series after 56 months of fol-low-up. On evaluating the recurrence pattern we found 10 cases (35.7%) at locoregional level, 11 distant cases (39.3%), and 7 cases (25%) of mixed recurrences. The median for the disease-free interval was 3.5 months (range: 2.0-56.0) for locoregional recurrences, 8 months (range: 4.0-31.0) for distant recurrences, and 17 months (range: 8.0-41.0) for mixed recurrences.
Vol. 107, N.º 9, 2015 CHARACTERISTICS AND PATTERN OF RECURRENCE AFTER CURATIVE SURGERY IN OESOPHAGEAL CANCER 543
Rev esp enfeRm Dig 2015; 107 (9): 539-546
Tab
le II
. Un
ivar
iate
an
d m
ult
ivar
iate
an
alys
is: P
rog
no
stic
fac
tors
fo
r re
curr
ence
of
the
dis
ease
aft
er c
ura
tive
su
rger
y
Oes
opha
geal
can
cer
recu
rren
ce
No
Yes
pC
rude
H
Rd
Adj
uste
d H
Rd†
95%
CIe
(Adj
uste
d H
Rd†)
naM
ean
SDb
Med
ian
IQRc
naM
ean
SDb
Med
ian
IQRc
Age
(yea
rs)
2762
.49.
061
.054
.0-5
9.0
2860
.011
.757
.053
.0-7
1.0
0.54
0.99
0.98
0.94
-1.0
2
BMIf
2026
.23.
926
.323
.0-2
9.6
1924
.33.
523
.920
.4-2
7.0
0.05
0.87
0.91
0.79
-1.0
6
Cru
de C
harls
on’s
com
orbi
dity
inde
x27
1.2
1.7
0.0
0.0-
2.0
280.
80.
91.
00.
0-1.
00.
180.
880.
690.
45-1
.06
Oes
opha
geal
can
cer
recu
rren
ce p
roba
bilit
y (%
)p
Cru
de
HRd
Adj
uste
d H
Rd†
95%
CIe
(Adj
uste
d H
Rd†)
6 m
onth
s1
year
3 ye
ars
5 ye
ars
Gen
der
Mal
e18
.827
.143
.851
.6-
11
Fem
ale
14.3
42.9
42.9
27.6
0.73
1.20
0.45
0.11
-1.8
0
Gas
tro-
oeso
phag
eal r
eflux
*
No
20.6
29.4
44.1
54.7
-1
Yes
14.3
28.6
42.9
47.6
0.62
0.83
--
Smok
ing
and
alco
hol c
onsu
mpt
ion
No
7.1
25.0
32.1
43.9
-1
1
Yes
29.6
33.3
51.9
63.0
0.17
1.67
1.20
0.44
-3.2
3
Dys
phag
ia*
No
0.0
10.0
20.0
30.0
-1
Yes
22.7
34.1
50.0
58.1
0.07
2.67
--
Wei
ght
loss
*
No
8.3
22.2
36.1
49.3
-1
Yes
38.9
44.4
61.1
61.1
0.12
1.86
--
His
topa
thol
ogic
cel
l typ
e
Squa
mou
s-ce
ll ca
rcin
oma
20.5
28.2
43.6
53.2
-1
1
Ade
noca
rcin
oma
12.5
31.3
43.8
50.0
0.92
0.96
2.50
0.82
-7.6
1
TNM
cla
ssifi
catio
n
Stag
es 0
-II8.
012
.016
.030
.0-
11
Stag
es II
I-IV
20.8
25.0
33.3
-0.
072.
008.
492.
75-2
6.22
Trea
tmen
t
Surg
ery
24.2
33.3
39.4
50.5
-1
1
Surg
ery
and
chem
othe
rapy
and
/or
radi
othe
rapy
9.1
22.7
50.0
54.5
0.84
1.08
1.17
0.40
-3.3
8
na : N
umbe
r of
pat
ient
s; S
Db :
Sta
ndar
d de
viat
ion;
IQRc :
Inte
r-qu
artil
e ra
nge;
HRd :
Haz
ard
Ratio
; C
Ie : C
onfid
ence
inte
rval
; BM
If : Bo
dy m
ass
inde
x; *
Sym
ptom
s/si
gns
befo
re o
esop
hage
al c
ance
r di
agno
sis;
†:
Mul
tivar
iate
re
gres
sion
ana
lysi
s ad
just
ing
for:
Gen
der,
age,
BM
I, C
rude
Cha
rlson
’s co
mor
bidi
ty in
dex,
sm
okin
g an
d al
coho
l con
sum
ptio
n, h
isto
phat
holo
gic
cell
type
, TN
M c
lass
ifica
tion
and
trea
tmen
t.
544 E. RODRÍGUEZ-CAMACHO ET AL. Rev esp enfeRm Dig (maDRiD)
Rev esp enfeRm Dig 2015; 107 (9): 539-546
Management of patients with recurrence, and post-recurrence survival
Once recurrence had been detected, treatment with chemo-therapy was given to 4 patients (14.3%), with radiotherapy to 8 patients (28.6%), and a combination of both in 1 patient (3.6%). A self-expanding oesophageal stent was fitted to 1 patient (3.6%), and the remaining 14 patients (50.0%) were given palliative management. The median post-recurrence sur-vival rate was 4.7 months. In the case of patients who received palliative care or an oesophageal stent, the median post-re-currence survival rate was 2.9 months, however in the case of the patients who received chemotherapy, radiotherapy or a combination of both, the post-recurrence survival rate reached 6.5 months (p = 0.074). The global post-recurrence survival curve and the curve for each treatment are shown in figure 3.
DISCUSSION
The recurrence of oesophageal cancer after curative sur-gery continues to be high. In this study, out of the total of
57 patients who underwent curative surgery, 50.9% had some kind of recurrence (locoregional recurrence and/or distant metastasis). This percentage concurs with those from other series published in Europe, in countries such as Great Britain, the Netherlands, France or Spain (7-10,13,16), or in Asia, in countries such as Japan or China (5,6,11,12).
After one year of follow-up, 53.6% of all of the recur-rences were detected; 82.1% after two years, and 85.7% after three years. The last recurrence documented in our series was after 56 months (4 years and 8 months) of fol-low-up. These results concur with those obtained by Abate et al. (14) in 2010, where 56% of the recurrences were detected in the first year of follow-up, 82% in the sec-ond year and 93% in the third year. Lou et al. (15) in a recently published study found that 54% of recurrences were detected in the first year of follow-up and 75% in the second year. Other series published at international level (4,10,16) concur in concluding that the majority of recur-rences are detected during the first 2 years of follow-up.
The majority of the studies analysed (5,6,8-14,16) have found that the degree of tumour invasion, as well as the presence of metastatic lymph, are variables that are asso-
Fig. 2. Recurrence probability for patients with oesophageal cancer after curative surgery according to tumour stage at diagnosis.
Vol. 107, N.º 9, 2015 CHARACTERISTICS AND PATTERN OF RECURRENCE AFTER CURATIVE SURGERY IN OESOPHAGEAL CANCER 545
Rev esp enfeRm Dig 2015; 107 (9): 539-546
ciated with the recurrence of the disease, and similarly, in our study the patients with higher stages had a higher probability of recurrence.
The median for the disease-free interval in our study was 8.5 months (range: 2.0-56.0). Generally, the value for this interval is closer to one year of follow-up, as seen in the studies of Hulscher et al. (7) in the Netherlands, Dresner et al. (8) in the United Kingdom, Nakagawa et al. (11) in Japan, and Abate et al. (14) in California, with disease-free intervals with a median of 11 months, or in the studies of Mariette et al. (9) in France, Sánchez-Pernaute et al. (10) in Madrid or Chen et al. (12) in China, with a median disease-free interval of 12 months. However, in a study from Japan in 2012, Sugiyama et al. (4) found a
median of 8.6 months (range: 1.1-48.0), a figure that was very close to that of our population (Table III).
The prognosis for patients with recurrence is general-ly poor, with post-recurrence survival data of less than 12 months (6,9,12,14), varying between the median of 2.7 months from the study by Dresner et al. (8) in the UK, to the median of 11 months from the study of Lou et al. (15) in New York. In our study, the median for the post-recurrence survival rate was 4.7 months. Despite not finding any statistically significant differences, the post-re-currence survival rate in the patients who underwent more intensive treatment was significantly higher. Similar results were found by Abate et al. (14) in their study from 2010, where the median for the post-recurrence survival rate was 9 months in treated patients, compared to 3 months for patients who did not receive any treatment.
We believe that the limitations of this study are the fact that we do not have tumour markers that could play an important role in the prognosis of oesophageal cancer, and which would help to identify and predict the prognosis of this tumour, as well as to adapt the treatment individually to each patient.
In turn, we have verified that our results concur with those from more extensive series published at international level (8,9,13,14).
It is important to note that in our study we used the competitive risk methodology, which is appropriate for analysing the behaviour of a person who may experience different events during the follow-up of the disease, and that we also provide data on oesophageal cancer, an illness that has a high incidence and mortality rate, and for which there is little data at population level in our region.
CONCLUSIONS
This study shows that the recurrence of oesophageal cancer is very frequent, despite undergoing curative sur-gery. Most recurrences will occur during the 2 years after surgery, meaning that strict follow-up is essential during this period. After diagnosis of a recurrence the prognosis is poor, which means that subsequent studies are necessary to evaluate the different treatments, as well as the different tumour and genetic markers, in order to individually adapt the treatment to these patients.
ACKNOWLEDGMENTS
This study was partially supported by the Post-Special-ization Scholarship of the Professor Novoa Santos Foun-dation (A Coruña, Spain).
Fig. 3. Overall survival and treatment-specific Kaplan-Meier survival curves after recurrence in patients with oesophageal cancer who underwent curative surgery.
Surv
ival
pro
babi
lity
Surv
ival
pro
babi
lity
Time from diagnosis of recurrence (months)
Time from diagnosis of recurrence (months)
Chemotherapy and/or radiotherapy
Palliative treatment
p = 0,074
546 E. RODRÍGUEZ-CAMACHO ET AL. Rev esp enfeRm Dig (maDRiD)
Rev esp enfeRm Dig 2015; 107 (9): 539-546
REFERENCES1. Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v1.2, Cancer
Incidence and Mortality Worldwide: IARC CancerBase No.10 [Inter-net]. Lyon, France: International Agency for Research on Cancer 2010. [acceso:29.10.2013]. Disponible en: http://globocan.iarc.fr.
2. Stahl M, Mariette C, Haustermans K, et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24(Supl. 6):vi51-6. DOI: 10.1093/annonc/mdt342
3. Wolf MC, Stahl M, Krause BJ, et al. Curative treatment of oesophageal carcinoma: Current options and future developments. Radiat Oncol 2011;6:55. DOI: 10.1186/1748-717X-6-55
4. Sugiyama M, Morita M, Yoshida R, et al. Patterns and time of recur-rence after complete resection of esophageal cancer. Surg Today 2012;42:752-8. DOI: 10.1007/s00595-012-0133-9
5. Morita M, Kuwano H, Ohno S, et al. Characteristics and sequence of the recurrent patterns after curative esophagectomy for squamous cell carcinoma. Surgery 1994;116:1-7.
6. Bhansali MS, Fujita H, Kakegawa T, et al. Pattern of recurrence after extended radical esophagectomy with three-field lymph node dissec-tion for squamous cell carcinoma in the thoracic esophagus. World J Surg 1997;21:275-81. DOI: 10.1007/s002689900228
7. Hulscher JB, van Sandick JW, Tijssen JG, et al. The recurrence pattern of esophageal carcinoma after transhiatal resection. J Am Coll Surg 2000;191:143-8. DOI: 10.1016/S1072-7515(00)00349-5
8. Dresner SM, Griffin SM. Pattern of recurrence following radi-cal oesophagectomy with two-field lymphadenectomy. Br J Surg 2000;87:1426-33. DOI: 10.1046/j.1365-2168.2000.01541.x
9. Mariette C, Balon JM, Piessen G, et al. Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer 2003;97:1616-23. DOI: 10.1002/cncr.11228
10. Sanchez-Pernaute A, Perez Aguirre E, Hernando Trancho F, et al. Recur-rence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy. Rev Esp Enferm Dig 2003;95:197-201, 191-6.
11. Nakagawa S, Kanda T, Kosugi S, et al. Recurrence pattern of squa-mous cell carcinoma of the thoracic esophagus after extended radical
esophagectomy with three-field lymphadenectomy. J Am Coll Surg 2004;198:205-11. DOI: 10.1016/j.jamcollsurg.2003.10.005
12. Chen G, Wang Z, Liu XY, et al. Recurrence pattern of squamous cell carcinoma in the middle thoracic esophagus after modified Ivor-Lewis esophagectomy. World J Surg 2007;31:1107-14. DOI: 10.1007/s00268-006-0551-1
13. Smit JK, Pultrum BB, van Dullemen HM, et al. Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy. Am J Surg 2010;200:446-53. DOI: 10.1016/j.amjsurg.2009.12.006
14. Abate E, DeMeester SR, Zehetner J, et al. Recurrence after esophagec-tomy for adenocarcinoma: Defining optimal follow-up intervals and testing. J Am Coll Surg 2010;210:428-35. DOI: 10.1016/j.jamcoll-surg.2010.01.006
15. Lou F, Sima CS, Adusumilli PS, et al. Esophageal cancer recur-rence patterns and implications for surveillance. J Thorac Oncol 2013;8:1558-62. DOI: 10.1097/01.JTO.0000437420.38972.fb
16. Lopez-Sebastian J, Marti-Obiol R, Lopez-Mozos F, et al. Recur-rence of esophageal cancer after R0 surgery. Risk factors and evolu-tion. Rev Esp Enferm Dig 2013;105:318-25. DOI: 10.4321/S1130-01082013000600002
17. Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer Staging Manual: Esophagus and esophagogastric junction. Ann Surg Oncol 2010;17:1721-4. DOI: 10.1245/s10434-010-1024-1
18. Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: Communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer 2010;116:5336-9. DOI: 10.1002/cncr.25537
19. Kalbfleisch J, Prentice R. The Statistical Analysis of Failure Time Data. John Willey and Sons, New York; 1980.
20. Gray RJ. A class of K-sample tests for comparing the cumulative inci-dence of a competing risk. The Annals of Statistics 1988;16:1141-54 DOI: 10.1214/aos/1176350951
21. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. JASA 1999;94:496-509. DOI: 10.1080/01621459. 1999.10474144
Table III. Summary of the literature review on the recurrence of oesophageal cancer
Author Year Country na %Prognostic
factors
Time from surgery to recurrence
Median (months)
Recurrence
1 year 2 years 3 years
2014 Coruña (Spain) 57 50.9 TNM 11 (range: 1.8-56.0) 57.1% 82.1% 85.7%
Morita (5) 1994 Japan 187 50.8% N, TNM 4.7-27.6
Bhansali (6) 1997 Japan 90 43.0% T, NMean = 11 (range:
1.0-59.0)
Hulscher (7) 2000 The Netherlands 149 52.6% TNM 11 (1.4-62.5)
Dresner (8) 2000 United Kingdom 176 48.0% T, N 11.7 (range: 1.5-67) 50%
Mariette (9) 2003 France 439 52.4% TNM 12 (range: 6-96) 45.7% 90%
Sánchez-Pernaute (10) 2003 Madrid (Spain) 92 44.7% T, N, 12 75% 100%
Nakagawa (11) 2004 Japan 174 43.3% T, N 11
Chen (12) 2007 China 196 48.9% T, N 12.2 (range: 2.4-35.6) 100%
Smit (13) 2010 The Netherlands 202 58.9% N 28% 44%
Abate (14) 2010 California (EEUU) 590 40.0% TNM 11 (range: 3.0-72.0) 56% 82% 93%
Sugiyama (4) 2012 Japan 208 29.3% 8.6 (range: 1.1-48.0) 71% 84%
Lou (15) 2013 New York (EEUU) 1147 38.0% Treatment 54% 75%
López-Sebastián (16) 2013 Valencia (Spain) 61 49.2% TNM 10.5 (range: 7.0-68.0) 90%
na: Number of patients.