MIE vs. Open Esophagectomy for Esophageal Cancer: A Population Study

Minimally Invasive Versus Open Esophagectomy
for Esophageal Cancer: A Population-Based
Analysis
Babatunde A. Yerokun, MD, Zhifei Sun, MD, Chi-Fu Jeffrey Yang, MD,
Brian C. Gulack, MD, Paul J. Speicher, MD, Mohamed A. Adam, MD,
Thomas A. D’Amico, MD, Mark W. Onaitis, MD, David H. Harpole, MD,
Mark F. Berry, MD, and Matthew G. Hartwig, MD
Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Surgery, Division of Cardiovascular
and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina; and Department of Cardiothoracic Surgery, Stanford
University, Stanford, California
Background. The objective of this study was to evaluate outcomes of minimally invasive approaches to
esophagectomy using population-level data.
Methods. Multivariable regression modeling was
used to determine predictors associated with the use
of minimally invasive approaches for patients in the
National Cancer Data Base who underwent resection of
middle and distal clinical T13N03M0 esophageal cancers from 2010 to 2012. Perioperative outcomes and
3-year survival were compared between propensitymatched groups of patients with esophageal cancer
who underwent minimally invasive esophagectomy
(MIE) or open esophagectomy (OE). A subgroup analysis was performed to evaluate the impact of using
robotic-assisted operations as part of the minimally
invasive approach.
Results. Among 4,266 patients included, 1,308 (30.6%)
underwent MIE. It was more likely to be used in patients
treated at academic (adjusted odds ratio [OR], 10.1;
95% confidence interval [CI], 4.2–33.1) or comprehensive
cancer facilities (adjusted OR, 6.4; 95% CI, 2.6–21.1).
Compared with propensity-matched patients who underwent OE, patients who underwent MIE had significantly more lymph nodes examined (15 versus 13;
p [ 0.016) and shorter hospital lengths of stay (10 days
versus 11 days; p [ 0.046) but similar resection margin
positivity, readmission, and 30-day mortality (all p > 0.05).
Survival was similar between the matched groups at
3 years for both adenocarcinoma and squamous cell
carcinoma (p > 0.05). Compared with MIE without robotic
assistance, use of a robotic approach was not associated
with any significant differences in perioperative outcomes (p > 0.05).
Conclusions. The use of minimally invasive techniques to perform esophagectomy for esophageal cancer
is associated with modestly improved perioperative outcomes without compromising survival.
O
the technical difficulties encountered in laparoscopic
resections, but data comparing RAMIE versus standard
MIE without robotic assistance (SMIE) are lacking.
The only study comparing RAMIE versus SMIE found no
differences in operative time, blood loss, number of
resected lymph nodes, postoperative complications,
days of mechanical ventilation, length of intensive care
unit stay, or length of hospital stay [4].
Despite the ongoing adoption of MIE, data regarding
the oncologic acceptability of using a minimally invasive
approach in esophageal cancer is extremely limited.
Most comparative effectiveness studies are single highvolume institutional experiences that lack generalizability [5–8]. The Traditional Invasive Versus Minimally
Invasive Esophagectomy (TIME) trial is the only
ver the past decade, minimally invasive esophagectomy (MIE) has been used increasingly for the
treatment of esophageal cancer [1]. Currently, MIE can be
performed through the laparoscopic transhiatal, the
laparoscopic-thoracoscopic McKeown, or the laparoscopicthoracoscopic Ivor Lewis approach [2]. Although there
are differences in the specific operative approach, supporters of MIE have cited reduced perioperative
morbidity, shortened hospital stay, and improved patient
satisfaction when compared with traditional open esophagectomy (OE) [3].
More recently, robotic-assisted minimally invasive
esophagectomy (RAMIE) has been introduced to address
Accepted for publication Feb 16, 2016.
Presented at the Forty-first Annual Meeting of the Western Thoracic
Surgery Association, Whistler, British Columbia, Canada, June 24–
27, 2015.
Address correspondence to Dr Hartwig, Duke University Medical Center,
Box 3863, Durham, NC 27710; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons
Published by Elsevier
(Ann Thorac Surg 2016;-:-–-)
Ó 2016 by The Society of Thoracic Surgeons
Dr D’Amico discloses a financial relationship with
Scanlan.
0003-4975/$36.00
http://dx.doi.org/10.1016/j.athoracsur.2016.02.078
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Abbreviations and Acronyms
CI
MIE
OE
RAMIE
SMIE
=
=
=
=
confidence interval
minimally invasive esophagectomy
open esophagectomy
robotic assisted minimally invasive
esophagectomy
= standard minimally invasive
esophagectomy without robotic
assistance
multicenter randomized study comparing open esophagectomy versus MIE, but it lacks power to detect any
oncologic difference [9]. Moreover, although 1 population
study analyzed short-term outcomes between MIE and
OE in the United Kingdom [10], no study to date has
examined survival differences between MIE and OE on a
national level in the United States.
Therefore the purpose of this study was to compare
perioperative outcomes and survival in patients who underwent MIE versus traditional OE using population-level
data. Furthermore, we aimed to assess any differences
in using a robotic-assisted minimally invasive approach
over the standard MIE approach. The primary hypothesis
was that surgical approach would not be associated
with perioperative outcomes or 3-year survival.
Patients and Methods
The Duke University Institutional Review Board
approved this retrospective review of the National Cancer
Data Base. The National Cancer Data Base is jointly
administered by the American College of Surgeons and
the American Cancer Society and collects data from
greater than 1,500 cancer institutions. The database
currently contains records of 30 million patient records
and approximately 70% of newly diagnosed cancer cases
in the United States.
Patients with clinical T1-3any NM0 esophageal cancers
located in the middle and distal esophagus who underwent esophagectomy from 2010 to 2012 were included
in the study. MIE was defined by intent-to-treat criteria
as any operation involving either thoracoscopy or laparoscopy, including any hybrid or robotic-assisted
approach. Patients with nonmalignant pathologic conditions or missing surgical approach data were excluded.
The primary end point of our study was 3-year survival.
Secondary end points included positive surgical margins,
lymph nodes examined, hospital length of stay, 30-day
unplanned readmissions, 30-day mortality, and adjuvant
therapy use.
Baseline characteristics between all cases of OE and
MIE were compared using the Kruskal-Wallis and Pearson’s c2 tests for continuous variable and categorical
variables, respectively. Multivariable logistic regression
models were developed to identify factors independently
associated with the use of OE versus MIE; a backward
variable elimination method was used to produce the
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most parsimonious model based on the lowest Akaike
information criterion. To adjust for potential selection
bias between the comparison of OE and MIE, we developed propensity scores, defined as the conditional probability of undergoing MIE. Patients were matched using
a 1:1 nearest-neighbor algorithm, using the following
variables: age, sex, race, insurance status, Charlson-Deyo
comorbidity score, treatment facility type (community,
comprehensive, or academic), location of the primary
lesion (middle or lower third of the esophagus), American
Joint Committee on Cancer clinical T and N stages,
tumor size, and use of simultaneous neoadjuvant chemotherapy and radiotherapy. Outcomes were compared in
propensity-matched groups. Survival was plotted using
the Kaplan-Meier method.
To assess the effect of robotic assistance in MIE,
a subgroup analysis was performed in a similar fashion
comparing RAMIE versus SMIE. This method was
repeated for both adenocarcinoma and squamous cell
carcinoma. For all analyses, p values less than 0.05
were considered to indicate statistical significance. All
analyses were performed using R, version 3.0.1 (The
R Foundation for Statistical Computing, Vienna, Austria).
Results
Among 4,266 total patients identified, 2,958 (69.3%)
underwent OE, whereas 1,308 (30.7%) underwent MIE.
Among patients who received MIE, 231 (17.6%) underwent RAMIE.
Unadjusted baseline characteristics of patients who
underwent OE and MIE are shown in Table 1. Patients
who underwent MIE were more likely to be treated at an
academic facility (p < 0.001), to have a lower clinical
T stage (p ¼ 0.029), to have a lower pathologic T stage
(p ¼ 0.041), and to have a smaller tumor size (p ¼ 0.007)
when compared with patients undergoing OE. Conversion to an open procedure within the entire MIE group
was 11.6%. The use of MIE increased from 27.1% in
2010 to 37.5% in 2012. The median number of esophagectomies per center was 2. After accounting for patient,
tumor, and hospital factors, we found that treatment
at either a comprehensive facility (odds ratio [OR], 7.32,
95% confidence interval [CI], 2.28–23.47; p ¼ 0.001) or an
academic facility (OR, 11.24; 95% CI, 3.52–35.90; p < 0.001)
was predictive of a patient undergoing MIE (Fig 1). Independent predictors of OE included the presence of
a clinical stage T2 tumor (OR, 0.74; 95% CI, 0.58–0.96;
p ¼ 0.023) or a clinical stage T3 tumor (OR, 0.72; 95% CI,
0.56–0.93; p ¼ 0.011), when compared with clinical stage
T1 disease (Fig 1).
After propensity matching, no substantial differences
in covariates remained between groups (Table 2). Within
matched groups, we found that margin positivity, unplanned readmission, and 30-day mortality rates were
not significantly different between OE and MIE groups
(all p > 0.05). However, the MIE group was associated
with a higher number of lymph nodes harvested
(15 versus 13; p ¼ 0.016) and a modest decrease in hospital
length of stay (10 days versus 11 days; p ¼ 0.046) (Table 3).
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Table 1. Baseline Characteristics of OE Versus MIE and SMIE Versus RAMIE Groups
Variable
Age (y)
Sex
Male
Female
Race
White
Black
Other
Insurance status
None
Private
Government
Charlson-Deyo comorbidity index
0
1
2
Year of diagnosis
2010
2011
2012
Hospital location
Northeast
Midwest
South
West
Facility type
Community
Comprehensive
Academic
Primary tumor site
Lower third of esophagus
Middle third of esophagus
Histologic type
Squamous cell
Adenocarcinoma
Clinical T stage
T1
T2
T3
Clinical N stage
N0
N1
N2
N3
Pathologic T stage
T0/in situ
T1
T2
T3
T4
OE (n ¼ 2,958)
MIE (n ¼ 1,308)
57/64/70
57/64/70
83.6% (2,474)
16.4% (484)
84.1% (1,100)
15.9% (208)
93.7% (2,741)
4.5% (131)
1.8% (54)
94.8% (1,233)
3.8% (50)
1.3% (17)
2.0% (59)
45.0% (1,301)
53.0% (1,533)
1.9% (25)
47.9% (619)
50.2% (649)
70.7% (2,090)
23.3% (690)
6.0% (178)
70.9% (927)
23.5% (308)
5.6% (73)
35.6% (1,054)
32.3% (954)
32.1% (950)
27.1% (354)
35.4% (463)
37.5% (491)
20.6%
34.3%
32.9%
12.2%
28.2%
25.4%
30.5%
15.9%
p Value
0.596
0.707
SMIE (n ¼ 1077)
RAMIE (n ¼ 231)
57/64/70
56/64/70
84.0% (905)
16.0% (172)
84.4% (195)
15.6% (36)
95.1% (1019)
3.7% (40)
1.1% (12)
93.4% (214)
4.4% (10)
2.2% (5)
1.9% (20)
47.8% (509)
50.3% (535)
2.2% (5)
48.0% (110)
49.8% (114)
70.3% (757)
24.0% (258)
5.8% (62)
73.6% (170)
21.6% (50)
4.8% (11)
29.4% (317)
35.3% (380)
35.3% (380)
16.0% (37)
35.9% (83)
48.1% (111)
29.9%
25.3%
27.5%
17.3%
20.3%
25.5%
44.6%
9.5%
0.284
0.951
0.853
0.588
<0.001
<0.001
<0.001
(369)
(332)
(399)
(208)
<0.001
(322)
(273)
(296)
(186)
(47)
(59)
(103)
(22)
<0.001
2.7% (81)
35.3% (1,041)
61.9% (1,825)
0.3% (4)
26.5% (347)
73.2% (957)
89.0% (2,634)
11.0% (324)
89.2% (1,167)
10.8% (141)
22.1% (653)
77.9% (2,305)
20.0% (261)
80.0% (1,047)
11.4% (299)
25.7% (673)
62.9% (1,645)
14.5% (167)
25.6% (296)
59.9% (692)
51.0%
39.1%
8.5%
1.4%
(1,492)
(1,145)
(248)
(42)
52.6%
40.1%
6.4%
0.9%
(680)
(519)
(83)
(12)
18.9%
31.1%
17.0%
32.6%
0.5%
(494)
(812)
(443)
(852)
(12)
20.3%
34.9%
14.9%
29.3%
0.6%
(246)
(422)
(180)
(354)
(7)
0.649
0.884
0.39
0.22
(608)
(1,016)
(974)
(360)
p Value
0.148
0.4% (4)
27.5% (296)
72.1% (777)
0.0% (0)
22.1% (51)
77.9% (180)
88.9% (957)
11.1% (120)
90.9% (210)
9.1% (21)
20.1% (216)
79.9% (861)
19.5% (45)
80.5% (186)
14.1% (132)
26.5% (248)
59.4% (555)
15.9% (35)
21.8% (48)
62.3% (137)
53.0%
40.2%
6.1%
0.8%
(564)
(428)
(65)
(8)
50.7%
39.7%
7.9%
1.7%
(116)
(91)
(18)
(4)
19.6%
35.4%
15.1%
29.4%
0.6%
(194)
(350)
(149)
(291)
(6)
23.7%
32.9%
14.2%
28.8%
0.5%
(52)
(72)
(31)
(63)
(1)
0.867
0.362
0.119
0.843
0.029
0.335
0.063
0.373
0.041
0.732
(Continued)
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Table 1. Continued
Variable
Pathologic N stage
N0
N1
N2
N3
Pathologic M stage
M0
M1
Tumor size (mm)
Neoadjuvant chemoradiotherapy
Conversion to open operation
OE (n ¼ 2,958)
MIE (n ¼ 1,308)
p Value
SMIE (n ¼ 1077)
RAMIE (n ¼ 231)
0.874
67.1%
20.8%
8.4%
3.7%
(1,774)
(549)
(223)
(97)
66.6%
20.3%
9.1%
3.9%
(812)
(248)
(111)
(48)
0.778
66.3%
20.2%
9.5%
4.0%
(664)
(202)
(95)
(40)
67.9%
21.1%
7.3%
3.7%
(148)
(46)
(16)
(8)
0.111
99.3% (2,937)
0.7% (21)
20/35/50
62.3% (1,837)
...
99.7% (1,304)
0.3% (4)
19/30/50
61.3% (800)
11.6% (152)
0.007
0.504
...
p Value
0.354
99.6% (1,073)
0.4% (4)
19/30/50
59.8% (643)
13.0% (139)
100.0% (231)
0.0% (0)
20/30/50
68.0% (157)
12.1% (28)
0.657
0.021
0.727
Data are represented as percent (n) for categorical variables and Q1/median/Q3 for continuous variables unless otherwise specified.
MIE ¼ minimally invasive esophagectomy;
OE ¼ open esophagectomy;
Q1 ¼ first quartile;
minimally invasive esophagectomy;
SMIE ¼ standard minimally invasive esophagectomy.
When stratified by histologic type, 3-year survival
was similar between OE and MIE. For patients with
adenocarcinoma, 3-year survival was 49.4% versus
56.7% for OE and MIE, respectively (p ¼ 0.206) (Fig 2A).
For patients with squamous cell carcinoma, 3-year survival was 56.3% versus 54.7% for OE and MIE, respectively (p ¼ 0.870) (Fig 2C).
Robotic Versus Standard MIE Subgroup Analysis
When comparing MIE performed with or without robotic
assistance, patients treated with robotic MIE were
more likely to have received neoadjuvant chemoradiotherapy (68.0% versus 59.8%; p ¼ 0.021) but otherwise were not significantly different, including the rate of
conversion to open operations (Table 1). After propensity
matching, no substantial differences remained between
the 2 groups, likely meaning that these differences were
center specific (Table 2). Within matched groups, we
found no differences between RAMIE and SMIE in
Fig 1. Forest plot of factors associated with use of minimally
invasive esophagectomy (MIE).
Black squares represent odds ratios
for the independent association
of each factor with using MIE;
95% confidence interval bounds
are represented by the corresponding horizontal lines. Factors
to the right of the vertical line at
1.0 are independently associated
with using MIE. Patients receiving
care at an academic or comprehensive institution are associated
with use of minimally invasive
esophagectomies, whereas patients
with cT2 and cT3 tumors were
associated with use of open
esophagectomy (OE).
Q3 ¼ third quartile;
RAMIE ¼ robotic-assisted
positive resection margin, lymph nodes harvested, hospital length of stay, 30-day readmission, or 30-day mortality (all p > 0.05) (Table 3).
After stratification by histologic type, there were no
significant differences in 3-year survival between SMIE
and RAMIE for patients with adenocarcinoma (p ¼ 0.783)
(Fig 2B). However, patients with squamous cell carcinoma
who underwent RAMIE had statistically superior survival
(84% versus 56% at 2 years; p ¼ 0.034) (Fig 2D).
Comment
In this population-level analysis of a minimally invasive
approach to esophagectomy for esophageal cancer, we
observed significantly higher odds of MIE use in academic centers, suggesting that adoption of MIE remains
predominantly confined to academic and teaching institutions in the United States. Additionally, MIE is
associated with modest improvements in lymph node
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Table 2. Baseline Characteristics of OE Versus MIE and Laparoscopic Versus RAMIE Groups After Propensity Matching
Variable
Age (y)
Sex
Male
Female
Race
White
Black
Other
Charlson-Deyo comorbidity index
0
1
2
Facility type
Community
Comprehensive
Academic
Tumor size (mm)
Clinical T stage
T1
T2
T3
Clinical N stage
N0
N1
N2
N3
Primary tumor site
Lower third of esophagus
Middle third of esophagus
Neoadjuvant chemoradiotherapy
OE (n ¼ 928)
MIE (n ¼ 928)
StDiff
SMIE (n ¼ 170)
RAMIE (n ¼ 170)
StDiff
57/64/71
57/64/70
0.9%
56/63/69
56/64/70
8.9%
84.3% (782)
15.7% (146)
83.5% (775)
16.5% (153)
2.0%
2.0%
84.1% (143)
15.9% (27)
83.5% (142)
16.5% (28)
1.6%
1.6%
94.0% (872)
4.4% (41)
1.6% (15)
94.0% (872)
4.7% (44)
1.3% (12)
0
1.5%
2.9%
89.4% (152)
7.6% (13)
2.9% (5)
91.2% (155)
5.9% (10)
2.9% (5)
6.9%
7.5%
0
72.7% (675)
22.4% (208)
4.8% (45)
72.4% (672)
22.8% (212)
4.7% (44)
0.8%
1.0%
0.5%
75.3% (128)
19.4% (33)
5.3% (9)
75.9% (129)
20.0% (34)
4.1% (7)
1.5%
1.5%
5.9%
0.2% (2)
26.8% (249)
73.0% (677)
20/35/50
0.2% (2)
26.8% (249)
73.0% (677)
20/35/50
0
0
0
2.6%
0.0% (0)
22.9% (39)
77.1% (131)
22.5/35.0/50.0
0.0% (0)
22.9% (39)
77.1% (131)
20.0/35.0/50.0
0
0
0
3.2%
16.4% (152)
25.1% (233)
58.5% (543)
15.7% (146)
26.1% (242)
58.2% (540)
1.6%
2.2%
0.7%
14.1% (24)
25.9% (44)
60.0% (102)
16.5% (28)
22.9% (39)
60.6% (103)
5.6%
7.0%
1.2%
51.5%
41.7%
6.1%
0.6%
50.1%
42.5%
6.8%
0.6%
(465)
(394)
(63)
(6)
2.9%
1.5%
2.6%
0
51.2%
40.0%
8.2%
0.6%
50.6%
40.6%
8.2%
0.6%
1.2%
1.2%
0
0
90.5% (840)
9.5% (88)
63.7% (591)
4.4%
4.4%
1.6%
94.1% (160)
5.9% (10)
70.6% (120)
(478)
(387)
(57)
(6)
89.2% (828)
10.8% (100)
62.9% (584)
(87)
(68)
(14)
(1)
(86)
(69)
(14)
(1)
91.8% (156)
8.2% (14)
70.6% (120)
8.5%
8.5%
0
Data are represented as percent (n) for categorical variables and Q1/median/Q3 for continuous variables unless otherwise specified. Groups with standardized differences (StDiff) less than 10% were considered similar.
MIE ¼ minimally invasive esophagectomy;
OE ¼ open esophagectomy;
Q1 ¼ first quartile;
minimally invasive esophagectomy;
SMIE ¼ standard minimally invasive esophagectomy.
harvesting and hospital length of stay without compromising long-term survival. Finally, robotic assistance is
not associated with improved perioperative outcomes
over standard minimally invasive methods.
Regarding MIE, the current literature highlights
outcomes when confined to high-volume experienced
Q3 ¼ third quartile;
RAMIE ¼ robotic-assisted
surgeons and establishes the efficacy of MIE in the
management of esophageal pathologic conditions. However, our study attempts to establish the present-day
application of MIE and determine how effectively it is
being used. In the setting of academic institutions, Parameswaran and colleagues [11] and Schoppmann and
Table 3. Study Outcomes in Propensity-Matched OE Versus MIE and Laparoscopic Versus RAMIE Groups
Outcomes
Positive resection margin
Lymph nodes harvested (number)
Hospital length of stay (d)
30-d readmission
30-d mortality rate
OE (n ¼ 928)
MIE (n ¼ 928)
p Value
SMIE (n ¼ 170)
RAMIE (n ¼ 170)
p Value
5.5% (50)
8/13/20
8/11/16
6.7% (62)
3.7% (23)
7.0% (65)
9/15/21
8/10/14
7.0% (65)
3.0% (17)
0.176
0.016
0.046
0.792
0.497
4.1% (7)
11/16/22
8/10/13
8.9% (15)
2.7% (3)
6.5% (11)
11/16/21
8/10/14
5.9% (10)
3.7% (3)
0.333
0.954
0.835
0.292
0.677
Matched variables included age, sex, race, insurance status, Charlson-Deyo comorbidity score, treatment facility type, location of the primary tumor,
histologic type, American Joint Committee on Cancer clinical stage, tumor size, and use of neoadjuvant chemoradiotherapy. Data are represented
as percent (n) for categorical variables and Q1/median/Q3 for continuous variables unless otherwise specified.
MIE ¼ minimally invasive esophagectomy;
OE ¼ open esophagectomy;
Q1 ¼ first quartile;
minimally invasive esophagectomy;
SMIE ¼ standard minimally invasive esophagectomy.
Q3 ¼ third quartile;
RAMIE ¼ robotic-assisted
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Fig 2. Survival of open esophagectomy (OE) versus minimally
invasive esophagectomy (MIE)
and standard minimally invasive
esophagectomy (SMIE) versus
robotic-assisted minimally invasive esophagectomy (RAMIE),
stratified by histologic type. (A)
Adenocarcinoma: OE versus MIE;
(B) adenocarcinoma: SMIE versus
RAMIE; (C) squamous cell
carcinoma: OE versus MIE;
(D) squamous cell carcinoma:
SMIE versus RAMIE.
colleagues [12] both reported similar short-term outcomes between OE and MIE in Europe. Similarly, Luketich and associates [5] demonstrated that MIE is an
efficacious and safe operation in the United States. In
1,033 consecutive patients at a high-volume center, the
authors reported an exceptionally low mortality rate of
0.9%, with a median hospital stay of 8 days. On a population level, Mamidanna and coworkers [10] analyzed
7,502 patients who underwent OE and MIE (n ¼ 1,155) in
the United Kingdom and found no differences in 30-day
morbidity and mortality. Overall, there is consistent evidence that MIE can be performed by high-volume experts
in the field safely and without additional risk to the patient. In this study, even with a median number of
esophagectomies per center of only 2 per year, the outcomes again were similar and even slightly favored
MIE when comparing perioperative outcomes.
Conversely, comparative oncologic data in the literature are limited and inconclusive. Regarding lymph node
harvesting, several institutions report improved nodal
retrieval with MIE [11, 13, 14], with other studies showing
no significant differences [12, 15]. For long-term outcomes, Palazzo and colleagues [6] reported 5-year mortality data from 168 patients treated in a high-volume
academic institution and found a 2-fold survival advantage in patients treated with MIE (hazard ratio, 2.0).
Although the authors accounted for several important
patient and tumor variables, concerns were raised
regarding the reproducibility of the significant outcome
differences in these groups. Moreover, because of the
small sample sizes in previous institutional studies, any
disparities may be attributed to inadequate adjustment,
including hospital-level factors. Our study improves on
these limitations by analyzing data on a population level,
attenuating the effect of outliers in center outcomes.
In 2012, Biere and associates [9] published results from
the Traditional Invasive Versus Minimally Invasive
Esophagectomy (TIME) trial, the only randomized study
examining differences in outcomes between OE and MIE.
In the TIME trial, 115 patients from the United Kingdom
Ann Thorac Surg
2016;-:-–-
were randomized to either an open or minimally invasive
approach. Although the authors concluded that OE and
MIE were equivalent except for a decrease in perioperative pulmonary complications, the TIME trial was powered to demonstrate only differences in short-term
outcomes. It lacked the ability to look at other perioperative or oncologic outcomes. By examining patient outcomes on a population level, our study improves on the
power to detect small differences in survival in a multivariable fashion.
With respect to comparative differences in the
newest robotic approaches to esophagectomies, data are
limited as well. Weksler and coworkers [4] published
an institutional experience of 43 patients who underwent
MIE, including only 11 patients who underwent robotic
esophagectomies. Although the authors rightfully concluded that in their hands, robotic and nonrobotic approaches were equivalent, the sample size was small,
the results were unadjusted, and the study lacked any
oncologic data. Although our study similarly suffers
from this issue when analyzing robotic versus standard
MIE resections, we were able to account for known confounders in reporting our results.
Our study has several limitations that should be
acknowledged. First, as a limitation of our data set, specific approaches to MIE (McKeown, Ivor-Lewis, transhiatal) could not be captured. However, previous data
have shown similar oncologic outcomes from any of the
3 approaches despite differences in perioperative complications [16]. We were also unable to differentiate
between patients undergoing a hybrid approach (ie, laparoscopy combined with a minithoracotomy) versus a
complete MIE. The inability to account for these variables
allows for the possible introduction of unknown interactions and confounders. Second, our data set does not
capture specific complications, which precludes our study
from comparing perioperative outcomes with more
granularity and from comparing the rate of complications
related to approach. However, we used hospital length
of stay and readmission rates as surrogates, which previous studies have shown to be effective markers for
clinically significant perioperative complications [17].
Finally, our analysis was retrospective in nature and thus
subject to selection bias. Although we attempted to control for known clinical, socioeconomic, hospital, and tumor covariates through our propensity-matched analysis,
inherent differences between comparison groups may
still occur that would be best addressed with a sufficiently
powered randomized trial. For example, 2 different clinical trials in progress randomizing patients between
OE and MIE are the French MIRO (Oesophagectomie
Pour Cancer par Voie Conventionnelle ou Coelio-Assist
ee) trial [18] and the British ROMIO (Randomized
Oesophagectomy: Minimally Invasive or Open) trial [19].
Nonetheless, our study is the largest comparative effectiveness study of MIE to date to examine long-term
survival.
In conclusion, MIE is associated with modestly
improved perioperative outcomes without compromising
survival. Our results support the ongoing adoption of
YEROKUN ET AL
MIE VERSUS OE FOR ESOPHAGEAL CANCER
7
minimally invasive technologies in the surgical management of esophageal cancer.
Institutional funding was the
study. In addition, this work
Institutes of Health–funded
Network (B.C.G. and M.G.H.),
primary funding source for this
was supported by the National
Cardiothoracic Surgery Trials
5U01HL088953-05.
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