Articles

Open versus laparoscopic surgery for mid-rectal or low-rectal

cancer after neoadjuvant chemoradiotherapy
(COREAN trial): survival outcomes of an open-label,
non-inferiority, randomised controlled trial
Seung-Yong Jeong, Ji Won Park, Byung Ho Nam, Sohee Kim, Sung-Bum Kang, Seok-Byung Lim, Hyo Seong Choi, Duck-Woo Kim, Hee Jin Chang,
Dae Yong Kim, Kyung Hae Jung, Tae-You Kim, Gyeong Hoon Kang, Eui Kyu Chie, Sun Young Kim, Dae Kyung Sohn, Dae-Hyun Kim, Jae-Sung Kim,
Hye Seung Lee, Jee Hyun Kim, Jae Hwan Oh

Summary
Background Compared with open resection, laparoscopic resection of rectal cancers is associated with improved
short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare
survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer.
Methods The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant
chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between
April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 1880 years) with cT3N02M0 mid-rectal or
low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either
open or laparoscopic surgery. Randomisation was stratied by sex and preoperative chemotherapy regimen.
Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment
assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis
was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT0040951.
Findings We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170).
3 year disease-free survival was 725% (95% CI 650786) for the open surgery group and 792% (723846) for
the laparoscopic surgery group, with a dierence that was lower than the prespecied non-inferiority margin (67%,
95% CI 158 to 24; p<00001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic
group. No deaths were treatment related.
Interpretation Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative
chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use.
Funding National Cancer Center, South Korea.

Introduction
Findings from several randomised controlled trials have
conrmed that the long-term oncological safety of
laparoscopic resection is equivalent to that of open
resection for colon cancer, in terms of local recurrence
and overall survival.14 Additionally, laparoscopic
resection for colon cancer is associated with improved
short-term outcomes with no dierence in
complications, compared with open surgery. However,
little solid evidence exists in support of laparoscopic
resection for rectal cancer. Although some randomised
trials have reported that laparoscopic and open rectal
surgery have similar oncological outcomes, these
studies had either small or single-institution cohorts,
and the primary oncological endpoints were not longterm.58 A subset analysis of the Conventional versus
Laparoscopic Assisted Surgery In Colorectal Cancer
(CLASSIC) trial3 showed no signicant dierence in
long-term overall or disease-free survival between the
open and laparoscopic rectal surgery groups.
www.thelancet.com/oncology Vol 15 June 2014

Preoperative chemoradiotherapy is preferred to

postoperative chemoradiotherapy because it reduces
locoregional recurrence in patients with locally advanced
rectal cancer.9 However, no randomised trials have shown
that laparoscopic surgery after preoperative chemoradiotherapy is safe for patients with locally advanced
rectal cancer. We did this Comparison of Open versus
laparoscopic surgery for mid or low REctal cancer After
Neoadjuvant chemoradiotherapy (COREAN) trial to
compare the survival outcomes of open versus
laparoscopic surgery after preoperative chemoradiotherapy for patients with mid-rectal or low-rectal cancer.

Methods
Study design and participants
We did this open-label, non-inferiority, randomised
controlled trial between April 4, 2006, and Aug 26, 2009.
Short-term outcomes of the trial have been reported
previously.10 The study protocol is available online. We
enrolled patients aged 1880 years with mid-rectal or

Lancet Oncol 2014; 15: 76774

Published Online
May 16, 2014
http://dx.doi.org/10.1016/
S1470-2045(14)70205-0
See Comment page 680
Department of Surgery, Seoul
National University College of
Medicine, Colorectal Cancer
Center, Seoul National
University Cancer Hospital
(Prof S-Y Jeong MD,
J W Park MD), Division of
Medical Oncology and
Department of Internal
Medicine (Prof T-Y Kim MD),
Department of Pathology
(Prof G H Kang MD), and
Department of Radiation
Oncology (E K Chie MD), Seoul
National University Hospital,
Seoul, South Korea; Cancer
Research Institute, Seoul
National University, Seoul,
South Korea
(Prof S-Y Jeong, J W Park);
Biometric Research Branch,
Division of Cancer
Epidemiology and Prevention
(Prof B H Nam PhD, S Kim MS),
and Center for Colorectal
Cancer (H S Choi MD,
H J Chang MD, D Y Kim MD,
S Y Kim MD, D K Sohn MD,
D-H Kim MD, Prof J H Oh MD),
Research Institute and
Hospital, National Cancer
Center, Goyang, South Korea;
Department of Surgery
(S-B Kang MD, D-W Kim MD),
Department of Radiation
Oncology (Prof J-S Kim MD),
Department of Pathology
(H S Lee MD), and Department
of Internal Medicine
(J H Kim MD), Seoul National
University College of Medicine,
Seoul National University
Bundang Hospital, Seongnam,
South Korea; and Department
of Colon and Rectal Surgery
(S-B Lim MD) and Department
of Oncology (Prof K H Jung MD),
University of Ulsan College of

767

Articles

Medicine, Asan Medical Center,

Seoul, South Korea

1408 patients screened for eligibility

Correspondence to:
Prof Jae Hwan Oh, Center for
Colorectal Cancer, Research
Institute and Hospital, National
Cancer Center, 323 Ilsan-ro,
Ilsandong-gu, Goyang 410-769,
South Korea
jayoh@ncc.re.kr

379 with cT3N0-2 mid or low rectal

cancers eligible for inclusion

Open surgery
(n=170)

Laparoscopic
surgery
(n=170)

591 (99)

578 (111)

Age (years)
Sex
Men

39 excluded
19 refused to participate
6 distant metastasis
14 refused surgery

For the COREAN trial protocol

see http://ncc.re.kr/common/
downloadByFileURL.jsp?path=/
downloadFiles/Protocol179.pdf

340 patients randomly assigned

170 allocated to open surgery

170 received open surgery

0 lost to follow-up immediately

after discharge

170 included in analysis for primary

endpoint

170 allocated to laparoscopic surgery

168 received laparoscopic surgery

2 converted to open surgery

0 lost to follow-up immediately

after discharge

170 included in analysis for primary

endpoint

Women
Body-mass index (kg/m)

110 (65%)

110 (65%)

60 (35%)

60 (35%)

2408 (320)

2408 (321)

25

106 (62%)

107 (63%)

>25

64 (38%)

63 (37%)

ASA grade
I

65 (38%)

69 (41%)

II

98 (58%)

96 (56%)

III

7 (4%)

5 (3%)

Preoperative serum concentration of carcinoembryonic antigen (ng/mL)

5

154 (91%)

157 (92%)

>5

16 (9%)

13 (8%)

Clinical classication
cN0

52 (31%)

59 (35%)

cN+

118 (69%)

111 (65%)

Tumour distance from anal verge (cm)

03

46 (27%)

35 (21%)

36

59 (35%)

66 (39%)

69

65 (38%)

69 (41%)

156 (92%)

156 (92%)

Preoperative chemotherapy
Figure 1: Trial prole

low-rectal cancer who had received preoperative

chemoradiotherapy10 and were being treated at any one of
three participating Korean hospitals. Patients rectal
adenocarcinomas had been clinically diagnosed as
cT3N02M0 lesions on the basis of abdominal and pelvic
CT, MRI, and transanal ultrasound. Exclusion criteria
were synchronous distant metastases, another primary
malignancy, cardiopulmonary dysfunction, active
uncontrolled infection, active uncontrolled psychosis,
and intestinal perforation or obstruction.
The trial was approved by the institutional review board
of each participating centre, and all patients provided
written informed consent.

Randomisation and masking

Patients were randomly allocated to the open or
laparoscopic resection group (1:1) via a computergenerated list with a random permuted block design.
The random allocation sequence was generated by the
Centre for Clinical Trials at the National Cancer Centre
Korea. Randomisation was stratied according to sex
and preoperative chemotherapy regimen. Local
investigators enrolled the patients. Investigators were
masked to the randomisation sequence, and
randomisation was done at the coordinating centre by
telephone. Patients and clinicians could not be masked
to treatment assignments. However, during the followup period, radiologists and pathologists were masked to
the procedural allocation.
768

Fluoropyrimidines alone
Doublet*

1 (1%)

3 (2%)

Triplet

13 (8%)

11 (6%)

149 (88%)

149 (88%)

Postoperative chemotherapy
Fluoropyrimidines alone
Oxaliplatin-based
None

13 (8%)

11 (6%)

8 (5%)

10 (6%)

Data are mean (SD) or n (%). ASA=American Society of Anesthesiologists.

*Capecitabine and irinotecan. Capecitabine, irinotecan, and cetuximab.

Table 1: Baseline characteristics

Procedures
Radiotherapy was delivered to the whole pelvis at a dose
of 45 Gy in 25 fractions, followed by a boost to the primary
tumour of 54 Gy in three fractions during 55 weeks.
One of three chemotherapeutic regimens was used for
preoperative chemoradiotherapy: (1) uoropyrimidines
alone (5-uorouracil and leucovorin or capecitabine or
tegafur-uracil [UFT-E]) and leucovorin; (2) doublet
(capecitabine and irinotecan); (3) triplet (capecitabine,
irinotecan, and cetuximab).10 Open or laparoscopic
resection was done 68 weeks after completion of
preoperative chemoradiotherapy. All patients underwent
radical proctectomy, including high ligation of the
inferior mesenteric vessels and total mesorectal excision.
Laparoscopic surgery was done with ve trocars. The
rectum was mobilised with monopolar cautery or an
ultrasonic scalpel, dissecting between the visceral and
parietal pelvic fascia without injuring the hypogastric
nerves. All surgeons did both open and laparoscopic
www.thelancet.com/oncology Vol 15 June 2014

Articles

procedures. At each hospital, three pathologists (HJC,

GHK, and HSL) who were masked to group allocation,
examined the surgical specimen according to
standardised protocol.10
Postoperative adjuvant chemotherapy was recommended for all patients, irrespective of the surgical
pathology results, in accordance with both the National
Comprehensive Cancer Network (NCCN) and Korean
NCCN guidelines.11 From week 4 after surgery, one of
three adjuvant chemotherapeutic regimens was delivered
for 4 months: (1) 5-uorouracil and leucovorin (four
cycles of an intravenous bolus injection of 5-uorouracil
[400 mg/m/day] and leucovorin [20 mg/m per day] on
days 15 every 4 weeks); (2) capecitabine (six cycles of
capecitabine [1250 mg/m] twice daily for 14 days,
followed by 7 days rest for each cycle); or (3) FOLFOX
(eight cycles of oxaliplatin [85 mg/m/day] on day 1,
5-uorouracil intravenous bolus [400 mg/m per day]
on day 1, and continuous infusion of 5-uorouracil
[2400 mg/m] for 46 h every 2 weeks).
Patients were followed-up at 3 months for the rst
2 years, at 6 months for the next 3 years, and at 6 months
or yearly thereafter. For the postoperative follow-up, a
physical examination, complete blood-cell count, liver
function tests, serum carcinoembryonic antigen tests,
and chest radiography were done every 3 months or
6 months; abdominal and pelvic CT were done every
6 months. Colonoscopic examinations were done 1 year
postoperatively and once every 2 years thereafter. When a
patient missed two consecutive scheduled visits or
voluntarily withdrew consent to participate during the
follow-up period, we regarded them as lost to follow-up.
Any loss to follow-up was censored. The last follow-up
was completed in August, 20123 years after the last
patient was randomised.

Open surgery
(n=170)

p value

Procedures
Abdominoperineal resection
Low anterior resection

24 (14%)

19 (11%)

146 (86%)

151 (89%)

042*

Tumour dierentiation
Well or moderately dierentiated

163 (96%)

164 (96%)

Poorly dierentiated, signet ring cell, or mucinous

6 (4%)

5 (3%)

Unknown

1 (1%)

1 (1%)

100

35 (21%)

25 (15%)

89 (52%)

74 (44%)

24 (14%)

31 (18%)

22 (13%)

40 (24%)

ypT0/ypTis/ypT1/ypT2

71 (42%)

95 (56%)

ypT3/ypT4

99 (58%)

75 (44%)

ypN0

113 (66%)

135 (79%)

ypN1

43 (25%)

18 (11%)

ypN2

14 (8%)

17 (10%)

Tumour regression grade scale

003*

ypT classication
001*

ypN classication
0002*

Circumferential resection margin

Positive (1 mm)

7 (4%)

5 (3%)

Negative (>1 mm)

163 (96%)

165 (97%)

077

Macroscopic quality of specimen from total mesorectal excision

Complete or nearly complete

150 (88%)

156 (92%)

Incomplete

11 (6%)

8 (5%)

Unknown

9 (5%)

6 (4%)

055*

Data are n (%). * test. Fishers exact test.

Table 2: Operative and pathological data

3-year survival (95% CI)

Outcomes

Disease-free survival

The primary outcome was disease-free survival 3 years

after surgery, dened as the time of randomisation to
disease progression, death from any cause, or
development of second primary cancer, and assessed by a
central independent reviewer. Secondary outcomes were
overall survival, local recurrence, and quality of life.
Events that negated disease-free survival were recurrence,
death from any cause, or a second primary cancer.
Recurrence was diagnosed pathologically by surgical
resection, or by biopsy or radiological detection of lesions
that increased in size over time. Radiologists and
pathologists independently assessed the radiological
imaging and pathological specimens. Local recurrence
was dened as any recurrence within the pelvic cavity or
the perineum. Systemic recurrence was dened as any
recurrence outside the pelvic cavity. Overall survival was
dened as time from surgery to death from any cause.
We used the validated Korean version of the European
Organization for Research and Treatment of Cancer
Quality-of-Life Questionnaire (EORTC QLQ)C30

Open surgery

725% (650 to 786)

Laparoscopic surgery

792% (723 to 846)

Dierence

67% (158 to 24)

www.thelancet.com/oncology Vol 15 June 2014

Laparoscopic
surgery
(n=170)

Overall survival
Open surgery

904% (849 to 940)

Laparoscopic surgery

917% (863 to 950)

Dierence

13% (74 to 48)

Local recurrence
Open surgery

49% (25 to 96)

Laparoscopic surgery

26% (10 to 67)

Dierence

23% (18 to 64)

Table 3: 3-year survival

questionnaire (version 3.0)12 and the colorectal cancer

module QLQCR3813 to assess quality of life preoperatively and at months 3, 12, 24, and 36 after
proctectomy or ileostomy takedownie, closure
(reversal) of ileostomyin patients who underwent
diverting ileostomy.
769

100

100
Disease-free survival (%)

Disease-free survival (%)

Articles

80
60
40
20

Open surgery
Laparoscopic surgery

0
0
Number at risk
Open surgery 170
Laparoscopic surgery 170

12

24

36

48

60

146
150

131
137

113
129

65
76

29
27

60
40
20

Open surgery
Laparoscopic surgery

0
Number at risk
Open surgery 62
Laparoscopic surgery 87

59
84

57
81

52
79

32
47

14
13

42
44

40
39

35
34

20
16

9
10

24

36

48

60

13
13

6
4

100
Disease-free survival (%)

100
Local recurrence (%)

80

80
60
40

80
60
40
20

20
0
0

0
Number at risk
Open surgery 170
Laparoscopic surgery 170

12

24

36

48

60

163
165

150
154

136
141

75
84

31
33

C
100
Disease-free survival (%)

C
100
Overall survival (%)

Number at risk
Open surgery 51
Laparoscopic surgery 48

80
60
40

80
60
40
20
0

20

12

Time since surgery (months)

0
0

12

24

36

48

60

Time since surgery (months)

Number at risk
Open surgery 170
Laparoscopic surgery 170

167
166

161
160

148
149

89
92

42
40

Figure 2: Kaplan-Meier curves showing disease-free survival (A), local

recurrence (B), and overall survival (C)

Statistical analysis
We estimated 3-year disease-free survival for open and
laparoscopic surgery to be 75% and set the noninferiority margin at 15%; the same margin was used in
a previous study.1 Thus, to show non-inferiority, the
upper limit of the 95% condence boundary of the
dierence (open minus laparoscopic surgery) in 3-year
disease-free survival between the two groups could not
exceed 15%. With 85% power and a one-sided type 1
error of 25%, we needed 340 patients (170 in each
group) to allow for 10% follow-up loss. We based all
analyses on the intention-to-treat population, which
included all randomised patients, and did not plan to
undertake interim analyses.
770

Number at risk
Open surgery 57
Laparoscopic surgery 35

45
22

34
17

26
16

Figure 3: Kaplan-Meier curves showing disease-free survival according to

tumour stage: stage 0/1 (A), stage 2 (B), and stage 3 (C)

We analysed operative and pathological variables with

the or Fishers exact test, dependent on variable
distribution. We used the Kaplan-Meier method to
estimate disease-free survival, overall survival, and local
recurrence; the log-rank test to compare survival
distribution; and univariate and multivariable Cox
regression models to estimate the hazard ratios (HRs)
of the treatment and covariates. We used multivariable
Cox regression analysis to adjust for confounding
factors that were signicant in univariate analysis and
for non-balanced between-group variables, and used
stratied Cox regression to estimate the HRs, with
incorporation of the stratication factors. We examined
the proportionality of the Cox regression models by
plotting logs of survival times (log [survival time])
and analysed QLQC30 and QLQCR38 scales with
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ANCOVA with repeated measures. We considered a

ten-point dierence in quality-of-life mean score as
clinically meaningful.14,15 All p values were two-sided.
All analyses were done with STATA (version 12). This
study was registered with ClinicalTrials.gov, number
NCT00470951.

Univariate analysis
Hazard ratio

Multivariable analysis
p value

Hazard ratio

<00001

133 (075237)

p value

ypT classication
ypT0/ypTis/ypT1/ypT2

100

ypT3/ypT4

288 (182455)

100
033

ypN classication

Role of the funding source

ypN0

100

The sponsor of this study had no role in study design,

data collection, data analysis, data interpretation, or the
writing of the report. The corresponding author had full
access to all the data in the study and had nal
responsibility for the decision to submit for publication.

ypN1

319 (195521)

<00001

246 (145419)

00009

ypN2

818 (4611451)

<00001

507 (259996)

<00001

Results
1408 patients were screened for eligibility, of whom we
randomly assigned 340 to receive either open surgery
(n=170) or laparoscopic surgery (n=170). 18 (5%) patients
did not receive postoperative adjuvant chemotherapy
because of refusal or postoperative complications. Two
(1%) patients in the laparoscopic proctectomy group who
required conversion to open proctectomy were kept in
the laparoscopic group for analysis (gure 1). The median
follow-up times were 46 months (IQR 3756) for the
open surgery group and 48 months (3857) for the
laparoscopic surgery group (p=047).
Baseline characteristics were similar between
treatment groups (table 1). Tumour dierentiation,
involvement of circumferential resection margin, and
macroscopic quality of total mesorectal excision
specimen were similar in both groups, but pathological
T and N classication, and tumour regression grade
diered signicantly (table 2). Table 3 shows the rates of
disease-free survival, overall survival, and local
recurrence for the two groups. No signicant dierence
was seen in 3 year disease-free survival (table 3, gure 2),
nor did the dierences exceed the 15% non-inferiority
margin (non-inferiority p<00001). The HR for diseasefree survival for the open versus the laparoscopic
surgery group, stratied by sex and preoperative chemotherapeutic regimen, was 123 (95% CI 081186).
Stage-specic analysis showed no dierence in diseasefree survival between treatment groups (gure 3);
overall survival or local recurrence rate likewise did not
dier signicantly (table 3, gure 2). The betweengroup HR was 125 (95% CI 069226) for overall
survival and 247 (077788) for local recurrence. The
3 year rate of disease-free survival for the laparoscopic
surgery group was likewise non-inferior to that of the
open surgery group in the per protocol analysis (data
not shown).
The number of combined events (ie, recurrence, death
without recurrence, or second primary cancer) was
49 (29%) in the open surgery group and 41 (24%) in the
laparoscopic surgery group. The number of patients that
had recurrences was 39 (23%) in the open surgery group
and 31 (18%) in the laparoscopic surgery group (log-rank
www.thelancet.com/oncology Vol 15 June 2014

100

Tumour regression grade scale

1

100

047 (030076)

0002

072 (043120)

100
021

025 (012053)

00003

048 (021110)

008

016 (007037)

<00001

044 (016121)

011

034

098 (063152)

Treatment group
Laparoscopic surgery

100

Open surgery

123 (081186)

100
094

Data in parentheses are 95% CIs. Stratied by sex and preoperative chemotherapeutic regimen.

Table 4: Univariate and multivariable Cox regression analyses for disease-free survival

p=031). The number of local recurrences, distant

recurrences, and combined recurrences at the time of
diagnosis was four, 29, and six, respectively, in the open
surgery group and two, 27, and two, respectively, in the
laparoscopic surgery group. The distribution of
recurrences did not dier between the groups (p=042),
and no tumour recurrence at the port or incision site was
noted in either group. 25 (15%) patients died in the open
surgery group and 20 (12%) died in the laparoscopic
surgery group. No deaths were treatment related. Of the
patients who died, 19 (76%) patients in the open surgery
group and 14 (70%) in the laparoscopic surgery group
died of rectal cancer. Despite randomisation, the two
groups diered in the distribution of pathological T and
N classication and tumour regression grade, but
multivariable analysis adjusted for those variables
showed no signicant dierence between groups
(table 4).
Compliance for the EORTC QLQ-C30 and QLQ-CR38
questionnaires were similar between patients in the open
surgery group and those in the laparoscopic surgery grou
2p (preoperatively 169 [99%] vs 165 [97%] patients;
postoperatively 124 [73%] patients at 12 months, 103 [61%]
at 24 months, and 82 [48%] at 36 months vs 126 [74%] at
12 months, 104 [61%] at 24 months, and 86 [51%] at
36 months). No clinically meaningful dierences were
seen because no scores diered by more than 10 points.

Discussion
We previously showed that circumferential resection
margin positivity, macroscopic quality of the total
mesorectal excision specimen, the number of harvested
lymph nodes, and perioperative morbidity did not dier
between laparoscopic and open surgery groups.10
771

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Findings from the present study show that laparoscopic

resection for locally advanced rectal cancer after
preoperative chemoradiotherapy is non-inferior to open
resection in terms of 3 year disease-free survival, overall
survival, and local recurrence (panel). The strengths of
our study include the registration of all eligible patients,
complete follow-up of all enrolled patients, and the high
level of skill of the surgeons involved.
Although ndings from several randomised
controlled trials68 suggest that long-term oncological
outcomes of laparoscopic total mesorectal excision are
non-inferior to those of open total mesorectal excision,
those trials were designed to compare short-term
outcome parametersnamely overall morbidity,6
analgesic requirements,7 or the number of lymph nodes
harvested.8 Because the sample size calculations were
based on short-term endpoints, their long-term
oncological outcomes were inconclusive. The primary
long-term endpoints of the CLASSIC trial3 were 3 year
overall survival, disease-free survival, and local
recurrence rate. However, the sample size calculation
for that trial was constrained by the need to obtain a
maximum number of cases in a reasonable period of
time. The number of enrolled patients with rectal
cancer in the CLASSIC trial16 is similar to the number
enrolled in our trial.10
To have been included in the COST, CLASSIC, or
COLOR trials,24 a surgeon must have operated on a
minimum of 20 laparoscopic colorectal cases, but the
CLASSIC trial investigators suggested that 20 cases was
not sucient because their open conversion rates fell
from 38% in year 1 to 16% in year 6.16 Laparoscopic
procedures are technically more demanding for rectal
cancer than for colon cancer because the surgical elds
for rectal surgery are conned by the narrow and deep
pelvis, and total mesorectal excision and autonomic
nerve preservation are prerequisites for functional and
oncological safety. For those reasons, a higher number
of minimum cases than previously required might be
necessary to minimise learning curve eects.1719
Furthermore, an assessment of the participating
surgeons level of technical prociency should be
mandatory. The most recently reported randomised trial
for laparoscopic versus open surgery for rectal cancer
(COLOR II) used a video review system to assess the
surgeons technical skills. A review of ve consecutive
unedited videos of laparoscopic total mesorectal excision
procedures by one of the lead investigators of the trial,
and a review of the pathology reports, were needed for a
surgeon to be judged qualied to participate in the
trial.20 Furthermore, the surgical techniques were
standardised by a review of other study surgeons
operations during video conferences or on-site before
enrolment began. The rst group of surgeons who were
involved at the beginning of the COREAN trial had
carried out at least 91 laparoscopic colorectal cancer
resections. Regarding laparoscopic total mesorectal
772

excision, the rst-group surgeons had achieved a

learning curve plateau through self-education and
mutual learning. Several studies have shown that the
eective self-taught learning curve is about
5080 laparoscopic rectal surgery cases.1719 These
surgeons were well-trained with respect to open total
mesorectal excision before the introduction of
laparoscopic total mesorectal excision. The second
group of surgeons were trained by the rst-group
surgeons through a fellowship-training programme.
The second-group surgeons joined the trial after their
procedures had been approved by the initial trial
surgeons. To assess competency with respect to open
total mesorectal excision, oncological parameters were
assessed, including the procedure quality and the rate of
circumferential resection margin involvement. The
second-group surgeons oncological techniques were
also assessed through a review of videotaped
laparoscopic colorectal surgeries. The learning curves of
second-group surgeons can be accelerated with the
supervision of senior specialist surgeons.21 The secondgroup surgeons had also reached a learning curve
plateau after undertaking the required minimum
number of surgeries.22 We consider all surgeons to have
possessed sucient surgical competencies for both
open and laparoscopic total mesorectal excision before
commencement of the trial.
This level of surgical experience, the standardised
surgical techniques, and the team approach, including
the rst assistants who actively participated in surgery
and specialised scope-manipulating assistants, might
have contributed to the low conversion rates. In the team
approach, the rst assistant was actively involved in all
laparoscopic procedures. For the total mesorectal
excision procedure, the assistant expedited rectal
dissection via rectal traction with a rectosigmoid colon
tie and countertraction of the pelvic wall with a fan
retractor. 23
In this trial, factors aecting surgical outcomes,
including sex and body-mass index, were well-balanced.
A weakness of the trial was that despite randomisation
and similar pre-treatment clinical stages, the
distribution of the pathological T and N classication
and tumour regression grade diered between the
laparoscopic and open groups. The laparoscopic group
had a higher ypN0 stage frequency and the open group
had fewer good responders (tumour regression
grade 3 or 4), which might have aected the long-term
oncological outcomes. The dierence in proportion
between both the groups happened by chance. We did
not note any bias in surgical technique randomisation.
The pathological T and N classications and tumour
regression grade could not be stratied before
randomisation. Such dierences might be avoided
through an increase in sample size, but that would
prolong the enrolment period and increase trial cost.
The best way to address this situation would be to
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Articles

adjust for those variables in the multivariable analysis.

The ongoing COLOR II trial20 has 1044 patientsthe
largest number of patients enrolled in a trial comparing
open and laparoscopic total mesorectal excision.
Although the number of patients in our trial was only a
third of that in the COLOR II trial, our trial focused on
locally advanced rectal cancer after preoperative
chemoradiotherapy, whereas COLOR II focused on all
rectal cancer without distant metastases, including
upper rectal cancer. A focus on a particular clinically
important outcome measure is emphasised because
unselective trials can dilute the eect of the intervention
and lead to failure of the trial or waste resources.24 Midrectal to low-rectal cancers below the peritoneal
reection with advanced stages are the most technically
challenging rectal tumours. However, the COLOR II
trial included tumours located 1015 cm from the anal
verge, which consisted of 33% of the tumours, and
stage I tumours, consisting of 30%.20 Generally,
participation of moderately competent community
surgeons in a randomised controlled trial is acceptable.
However, this principle might not apply ethically; in
rectal cancer surgery, for which surgical and oncologic
outcomes are highly dependent on the surgeons
prociency. Well-qualied colorectal surgeons could be
dened as surgeons who had reached a self-taught
learning curve plateau after undertaking an adequate
number of surgeries, or those who had been deemed
qualied by senior specialist surgeons after a review of
surgical videotapes to assess the surgeons oncological
techniques with respect to colorectal cancer.
Furthermore, the clinical setting for advanced rectal
cancer requires facilities for radiation and
chemotherapy, which restricts the range of participating
surgeons.
In patients with mid-rectal or low-rectal cancer treated
with preoperative chemoradiotherapy, laparoscopic
resection is considered a technically challenging
procedure. However, if laparoscopic procedures are
oncologically safe in such patients, laparoscopic resection
would be feasible for most rectal cancers except for
cT4 lesions or tumours with threatened circumferential
resection margins.
Adoption of laparoscopic rectal surgery may be low in
diverse health-care environments. However, laparoscopic
rectal surgery could be applied in other health-care
settings and ethnic groups, assuming that colorectal
surgeons with sucient experience would do the
surgeries. However, the dierences in health expenses
and insurance aect the selections of other surgical
modalities (eg, robotic surgery).
Our nding that long-term quality of life was similar
for the open and laparoscopic groups diered from
results of our previously reported short-term outcome,10
which showed that the laparoscopic group had a better
quality of life in terms of better physical functioning,
less fatigue, less micturition, and fewer gastrointestinal
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Panel: Research in context

Systematic review
We searched Embase, Web of Science, PubMed, and the
Cochrane Library for randomised controlled trials of
laparoscopic and open surgery in patients with rectal cancer.
We searched for trials published up to Dec 31, 2013, with the
following MeSH headings and combinations thereof: Rectal
Cancers, Colorectal Cancers, Laparoscopy, and their
variants. Results had been reported for seven previous trials of
patients with rectal cancer. However, these trials had either
small or single-institution cohorts and the primary endpoints
of most of the trials were not long-term oncologic outcomes.
The COLOR II trial was a well-designed, randomised controlled
trial with sucient patient numbers; however, its long-term
results have not yet been reported. Moreover, none of the
studies had assessed the safety of laparoscopic surgery after
preoperative chemoradiotherapy in patients with locally
advanced rectal cancer, although this is a presently accepted
and preferred treatment option for such patients.
Interpretation
To our knowledge, the COREAN trial provides the rst report
of long-term oncological outcomes of a randomised
controlled trial comparing open and laparoscopic surgery for
advanced rectal cancer, in which the primary endpoint was
the long-term oncological outcome. Furthermore, this was
the rst trial in which all patients received preoperative
chemoradiotherapy. Our results showed that laparoscopic
resection for locally advanced rectal cancer after preoperative
chemoradiotherapy was not inferior to open resection in
terms of the 3-year disease-free survival, overall survival, and
local recurrence rates, thus suggesting that a laparoscopic
approach for rectal cancer surgery could be justied when
done by well-qualied colorectal surgeons.

and defecation symptoms. Thus, the dierence was not

maintained in the long-term. Several other studies
reported improved short-term quality of life in patients
who underwent laparoscopic versus those who
underwent open total mesorectal excision,6,25,26 but none
had improved long-term quality of life, which is in line
with our ndings. The most recent COLOR II trial
study reported that quality of life after rectal cancer
surgery was not aected by surgical approach.27 Another
limitation of this trial was the loss to quality of life
follow-up with respect to the questionnaires. Practically,
this follow-up loss was inevitable. Collection of
questionnaires associated with cases of recurrence was
particularly dicult.
Findings from the COREAN trial showed that
laparoscopic resection for locally advanced rectal cancer
after preoperative chemoradiotherapy can provide noninferior survival outcomes to open surgery, suggesting a
laparoscopic approach can be justied for rectal cancer
surgery when done by well-qualied colorectal surgeons.
773

Articles

Declaration of interests
We declare no competing interests.
Contributors
S-YJ, BHN, S-BK, S-BL, YSC, DYK, and KHJ were responsible for the
study concept and design. S-YJ, JWP, S-BK, S-BL, HSC, D-WK, HJC,
DYK, KHJ, T-YK, GHK, EKC, SYK, DKS, D-HK, J-SK, HSL, JHK, and
JHO collected and assembled data. S-YJ, JWP, BHN, SK, S-BK, and JHO
analysed and interpreted data. S-YJ, JWP, BHN, S-BK, and JHO wrote
the report. SK, S-BL, HSC, D-WK, HJC, DYK, KHJ, T-YK, GHK, EKC,
SYK, DKS, D-HK, J-SK, HSL, and JHK revised the report. All authors
approved the nal draft for submission.
Acknowledgments
The COREAN trial was supported by a grant from the National Cancer
Centre (number 1210160).
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