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The n e w e ng l a n d j o u r na l of m e dic i n e

original article

A Randomized Trial of Laparoscopic


versus Open Surgery for Rectal Cancer
H. Jaap Bonjer, M.D., Ph.D., Charlotte L. Deijen, M.D., Gabor A. Abis, M.D.,
Miguel A. Cuesta, M.D., Ph.D., Martijn H.G.M. van der Pas, M.D.,
Elly S.M. de Lange-de Klerk, M.D., Ph.D., Antonio M. Lacy, M.D., Ph.D.,
Willem A. Bemelman, M.D., Ph.D., John Andersson, M.D.,
Eva Angenete, M.D., Ph.D., Jacob Rosenberg, M.D., Ph.D., Alois Fuerst, M.D., Ph.D.,
and Eva Haglind, M.D., Ph.D., for the COLOR II Study Group*

A bs t r ac t

Background
From VU University Medical Center (H.J.B., Laparoscopic resection of colorectal cancer is widely used. However, robust evi-
C.L.D., G.A.A., M.A.C., M.H.G.M.P., dence to conclude that laparoscopic surgery and open surgery have similar out-
E.S.M.L.-K.) and Amsterdam Medical
Center (W.A.B.) both in Amsterdam; comes in rectal cancer is lacking. A trial was designed to compare 3-year rates of
Hospital Clinic I Provincial de Barcelona, cancer recurrence in the pelvic or perineal area (locoregional recurrence) and sur-
Barcelona (A.M.L.); the Department of vival after laparoscopic and open resection of rectal cancer.
Surgery, Institute of Clinical Sciences,
Sahlgrenska Academy, University of Go-
thenburg, Sahlgrenska University Hospi- Methods
talstra, Gothenburg, Sweden (J.A., In this international trial conducted in 30 hospitals, we randomly assigned patients
E.A., E.H.); Herlev Hospital, Department
of Surgery, University of Copenhagen, with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not
Copenhagen (J.R.); and Caritas Kranken- invading adjacent tissues, and without distant metastases to undergo either laparo-
haus St. Josef, Regensburg, Germany scopic or open surgery in a 2:1 ratio. The primary end point was locoregional recur-
(A.F.). Address reprint requests to Dr.
Bonjer at VU University Medical Center, rence 3 years after the index surgery. Secondary end points included disease-free
Department of Surgery, De Boelelaan and overall survival.
1117, 1081 HV Amsterdam, the Nether-
lands, or at j.bonjer@vumc.nl.
Results
*
A complete list of members of the A total of 1044 patients were included (699 in the laparoscopic-surgery group and
Colorectal Cancer Laparoscopic or Open 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was
Resection (COLOR) II Study Group is
provided in the Supplementary Appen- 5.0% in the two groups (difference, 0 percentage points; 90% confidence interval
dix, available at NEJM.org. [CI], 2.6 to 2.6). Disease-free survival rates were 74.8% in the laparoscopic-surgery
N Engl J Med 2015;372:1324-32. group and 70.8% in the open-surgery group (difference, 4.0 percentage points; 95%
DOI: 10.1056/NEJMoa1414882 CI, 1.9 to 9.9). Overall survival rates were 86.7% in the laparoscopic-surgery group
Copyright 2015 Massachusetts Medical Society.
and 83.6% in the open-surgery group (difference, 3.1 percentage points; 95% CI,
1.6 to 7.8).

Conclusions
Laparoscopic surgery in patients with rectal cancer was associated with rates of
locoregional recurrence and disease-free and overall survival similar to those for
open surgery. (Funded by Ethicon Endo-Surgery Europe and others; COLOR II
ClinicalTrials.gov number, NCT00297791.)

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Laparoscopic vs. Open Surgery for Rectal Cancer

C
olorectal cancer is the third most authors analyzed the data and vouch for the ac-
common cancer worldwide and accounts curacy of the data and the analyses and the fidel-
for nearly 1.4 million new cases and ity of the study to the protocol (available with the
694,000 deaths per year. Approximately one third full text of this article at NEJM.org). The authors
of all colorectal cancers are localized in the rec- wrote the manuscript and made the decision to
tum.1-4 Less than a half century ago, rectal can- submit the manuscript for publication. The sponsor
cer had a poor prognosis, with cancer recurrence of the study, Ethicon Endo-Surgery Europe (a sub-
rates in the pelvic or perineal area (locoregional sidiary of Johnson & Johnson), had no role in the
recurrence) of up to 40% and 5-year survival study design, data gathering, analyses and inter-
rates after surgical resection of less than 50%.5,6 pretation, or writing of the manuscript.
In the 1980s, Heald and Ryall6 introduced a new
surgical technique of complete removal of the Patients
fatty envelope surrounding the rectum (mesorec- Patients with a solitary adenocarcinoma of the
tum), called total mesorectal excision. The adop- rectum within 15 cm from the anal verge without
tion of total mesorectal excision combined with distant metastases who were candidates for elec-
neoadjuvant chemoradiotherapy in selected pa- tive surgery were eligible for inclusion. The local-
tients has reduced locoregional recurrence rates ization of the tumor was categorized as the upper
to below 10% and improved cancer-free survival rectum (distal border of tumor, 10 to 15 cm from
rates to more than 70%.7-10 the anal verge), middle rectum (5 to 10 cm from
Laparoscopic surgery has progressively replaced the anal verge), or lower rectum (<5 cm from the
open colonic surgery in recent decades owing to anal verge). Patients with T4 tumors or T3 tumors
favorable short-term outcomes, such as less pain, within 2 mm of the endopelvic fascia, as deter-
reduced blood loss, and improved recovery time.11 mined on computed tomography (CT) or mag-
Initially, there was concern regarding the safety netic resonance imaging (MRI), were excluded.
of laparoscopic colectomy after reports of cancer Other exclusion criteria have been reported previ-
recurrence in the abdominal wall.12,13 In various ously.16 The study was approved by the institu-
trials in which patients with colon cancer were tional review board at each participating center.
randomly assigned to undergo either open or All patients provided written informed consent.
laparoscopic surgery, evidence was obtained that
laparoscopic surgery was associated with similar Randomization
disease-free and overall survival rates as open Randomization was performed at the patient
surgery.14,15 However, evidence is lacking from level. Laparoscopic and open surgery were per-
large, randomized clinical trials indicating that formed at all participating centers. Eligible pa-
survival after laparoscopic resection of rectal tients were randomly assigned in a 2:1 ratio to
cancer is not inferior to open surgery. We previ- undergo either laparoscopy or open surgery ac-
ously reported that laparoscopic surgery in pa- cording to a list of randomization numbers with
tients with rectal cancer was associated with treatment assignments. This list was computer-
similar surgical safety and improved recovery generated, with stratification according to hospi-
time, as compared with open surgery.16 In the tal, tumor location, and the presence or absence
Colorectal Cancer Laparoscopic or Open Resec- of preoperative radiotherapy. An Internet applica-
tion (COLOR) II trial, we report the long-term tion allowed central randomization.
rates of locoregional recurrence and survival in
patients who were randomly assigned to under- Procedures and Quality Control
go one of the two procedures. The use of neoadjuvant therapy was determined
by multidisciplinary cancer boards at each par-
Me thods ticipating hospital, according to local standards,
without differences between the laparoscopic-
Study Design and Oversight surgery group and the open-surgery group. All
The COLOR II trial was a noninferiority, open- procedures were required to comply with the
label, multicenter trial conducted at 30 centers in principles of total mesorectal excision or partial
8 countries. The study was designed by members mesorectal excision if the cancer was located in
of the protocol committee. The local investiga- the upper part of the rectum.6
tors and the trial manager gathered the data. The The selection of centers for participation in

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The n e w e ng l a n d j o u r na l of m e dic i n e

the trial was based on stringent quality assess- vals were calculated. In addition, we performed
ment by the study management committee to as-treated analyses for locoregional recurrence,
confirm the use of proper surgical technique. disease-free survival, and overall survival.
Unedited recordings of five consecutive laparo-
scopic total mesorectal excisions were evaluated. R e sult s
The respective pathology reports of these five
consecutive cases were reviewed to confirm Patients
completeness of the specimens. Pathologists From January 2004 through May 2010, a total of
adhered to standardized processing and assess- 1103 patients with rectal cancer underwent ran-
ment of specimens, as described in detail in the domization. Of these patients, 739 were assigned
trial protocol, to ensure accurate reporting by all to undergo laparoscopic surgery and 364 to un-
participating centers.16 The circumferential re- dergo open surgery. After the exclusion of 59 pa-
section margin was defined as involved when tients following randomization, 1044 patients
tumor cells were present within 2 mm from the (699 in the laparoscopic-surgery group and 345
lateral surface of the mesorectum. patients in the open-surgery group) were includ-
ed in the analysis (Fig. 1). In total, 1036 patients
End Points were included in the long-term analyses.
The primary end point was locoregional recurrence At the 3-year follow-up, data were available
3 years after the index surgery. Secondary end for 771 patients (74%) regarding locoregional
points included disease-free and overall survival. recurrence, 923 (89%) regarding disease-free
survival, and 903 (87%) regarding overall sur-
Follow-up vival. The clinical characteristics of the patients
Minimal required follow-up included annual clini- were similar in the two groups, as were the
cal examinations for 5 years after surgery. Three proportions of patients who received neoadju-
years after the index surgery, CT or MRI of the vant chemoradiotherapy (Table 1).
pelvis combined with imaging of the liver and
the chest were performed. Recurrent disease was Short-Term Outcomes
defined as the presence of locoregional recur- Five patients who were randomly assigned to the
rence, the presence of distant metastases, or open-surgery group underwent laparoscopic sur-
death from rectal cancer. gery. Of these patients, three requested laparo-
scopic surgery after randomization, and the rea-
Statistical Analysis son for crossover was unknown for the other two
We used the KaplanMeier method to estimate patients. In addition, seven patients in the lapa-
the difference in recurrence rates between the roscopic-surgery group underwent open surgery:
two study groups at 3 years postoperatively. Lapa- one owing to poor pulmonary condition, five
roscopic surgery was considered to be noninferior because no laparoscopic surgeon was available,
to open surgery if the one-sided 95% confidence and one for an unknown reason. A total of 86%
interval for the difference in locoregional recur- of laparoscopic and open procedures were per-
rence rates excluded an absolute difference of 5 per- formed by surgeons who had performed both
centage points or more. With 1000 patients who laparoscopic and open surgeries for rectal cancer.
could be evaluated at a ratio of 2:1, the power of The conversion rate from laparoscopic surgery to
the noninferiority test was 80% at a locoregional open surgery was 16%. In the laparoscopic-surgery
recurrence rate of 10% in the open-surgery group. group, the operating time was 52 minutes longer,
All analyses were performed on an intention- bowel function returned 1 day earlier, and the
to-treat basis. We used the KaplanMeier method hospital stay was 1 day shorter than in the open-
to compare rates of recurrence, disease-free sur- surgery group. There were no significant differ-
vival, and overall survival at 3 years. The one- ences in the rates of anastomotic leaking, com-
sided 95% confidence interval for the between- plication, or death.16
group difference in locoregional recurrence
corresponds to the upper limit of the two-sided Pathological Analyses
90% confidence interval for this difference. For There were no significant between-group differ-
survival rates, two-sided 95% confidence inter- ences for all lesions with respect to macroscopic

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Laparoscopic vs. Open Surgery for Rectal Cancer

1103 Patients underwent randomization

739 Were assigned to undergo 364 Were assigned to undergo


laparoscopic surgery open surgery

40 Were excluded 19 Were excluded


12 Had distant metastases 2 Had distant metastases
12 Did not have carcinoma 2 Did not have carcinoma
6 Had T4 tumor 7 Had T4 tumor
2 Died before surgery 7 Withdrew consent
1 Withdrew consent 1 Underwent emergency
7 Had other reasons operation

699 Were included in the analysis 345 Were included in the analysis
7 Underwent open surgery 5 Underwent laparoscopic surgery

Figure 1. Enrollment and Outcomes.

completeness of the mesorectum, involved cir- respectively (difference, 1.6 percentage points;
cumferential resection margins (Tables 1 and 2), 90% CI, 2.3 to 5.5); in patients with lower rec-
or distal resection margins (median, 3.0 cm in tal cancers, the rates were 3.8% and 12.7%, re-
the two groups). spectively (difference 8.9 percentage points;
90% CI, 15.6 to 2.2). Among 46 patients with
Locoregional Recurrence locoregional recurrence at 3 years, 27 patients
At 3 years, the rate of locoregional recurrence had distant metastases as well.
was 5.0% in each of the study groups (31 patients
in the laparoscopic-surgery group and 15 in the Disease-free and Overall Survival
open-surgery group) (Table 2). The upper limit of At 3 years, the rate of disease-free survival was
the 90% confidence interval for the absolute be- 74.8% in the laparoscopic-surgery group and
tween-group difference in the rate of locoregion- 70.8% in the open-surgery group (difference, 4.0
al recurrence (2.6 percentage points) was below percentage points; 95% CI, 1.9 to 9.9) (Fig. 2). In
the noninferiority margin of 5 percentage points. patients with stage I or II rectal cancer, rates of
In the intention-to-treat analysis, rates of loco- disease-free survival were similar in the two
regional recurrence of upper rectal cancers were groups, whereas in patients with stage III dis-
3.5% in the laparoscopic-surgery group and 2.9% ease, the rate of disease-free survival was 64.9%
in the open-surgery group (difference, 0.6 per- in the laparoscopic-surgery group and 52.0% in
centage points; 90% CI, 2.9 to 4.1). In patients the open-surgery group (difference, 12.9 percent-
with middle rectal cancers, locoregional recur- age points; 95% CI, 2.2 to 23.6).
rence rates were 6.5% and 2.4%, respectively (dif- At 3 years after surgery, 145 patients had
ference, 4.1 percentage points; 90% CI, 0.7 to 7.5); died, accounting for an overall survival rate of
in patients with lower rectal cancers, the rates 86.7% in the laparoscopic-surgery group and
were 4.4% and 11.7%, respectively (difference, 83.6% in the open-surgery group (difference, 3.1
7.3 percentage points; 90% CI, 13.9 to 0.7). percentage points; 95% CI, 1.6 to 7.8) (Fig. 3).
In the as-treated analysis, the locoregional Overall survival rates according to disease stage
recurrence rates in patients with upper rectal were also similar in the two groups.
cancers were 3.0% in the laparoscopic-surgery Distant metastases at 3 years after surgery
group and 3.9% in the open-surgery group (dif- were reported in 19.1% of the patients in the
ference, 0.9 percentage points; 90% CI, 4.6 to laparoscopic-surgery group and 22.1% of those
2.8). In patients with middle rectal cancers, loco in the open-surgery group, including one port-
regional recurrence rates were 5.7% and 4.1%, site metastasis in the laparoscopic-surgery group

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and one tumor recurrence in the laparotomy


Table 1. Clinical and Pathological Characteristics of the Patients at Baseline.*
wound in the open-surgery group.
Laparoscopic Surgery Open Surgery
Characteristic (N=699) (N=345)
Discussion
Sex no. (%)
Male 448 (64) 211 (61)
In this trial, we compared the rates of locoregional
Female 251 (36) 134 (39)
recurrence of rectal cancer after laparoscopic or
Age yr 66.810.5 65.810.9
open resection. Locoregional recurrences were
American Society of Anesthesiologists
classification no. (%)
recorded in 5.0% of the patients in each of the
I: healthy 156 (22) 65 (19) two groups. In the Dutch trial of total mesorectal
II: mild systemic disease 386 (55) 211 (61) excision by Kapiteijn et al.,8 among 1805 patients
III: severe systemic disease 131 (19) 61 (18) with rectal cancer who underwent open resection,
IV: severe life-threatening systemic 5 (1) 1 (<1) the locoregional recurrence rate at 2 years was
disease 5.3%, a rate similar to that in our study.
Missing data 21 (3) 7 (2) In the Conventional versus Laparoscopic-
Body-mass index 26.14.5 26.54.7 Assisted Surgery in Colorectal Cancer (CLASICC)
Distance of tumor from anal verge trial, the first multicenter, randomized study to
no. (%) determine the effect of laparoscopic surgery on
Upper rectum: 10 to 15 cm 223 (32) 116 (34) rectal-cancer outcomes involving 381 patients,
Middle rectum: 5 to <10 cm 273 (39) 136 (39) the locoregional recurrence rate at 3 years was
Lower rectum: <5 cm 203 (29) 93 (27) 9.7% after laparoscopic surgery and 10.1% after
Clinical stage no. (%) open surgery.17 The presence of involved cir-
I 201 (29) 96 (28)
cumferential resection margins, which predis-
II 209 (30) 107 (31)
pose patients to locoregional recurrence, were
III 257 (37) 126 (37)
observed in 16% of the patients after laparo-
Missing data 32 (5) 16 (5)
scopic surgery in the CLASICC trial, as com-
Preoperative radiotherapy no. (%) 412 (59) 199 (58)
pared with 10% of those in the laparoscopic-
Preoperative chemotherapy no./ 196/609 (32) 99/295 (34)
total no. (%)
surgery group in our study.18,19 Recently, in the
No residual tumor no./total no. 33/412 (8) 19/199 (10) Comparison of Open versus Laparoscopic Sur-
(%) gery for Mid or Low Rectal Cancer after Neoad-
Pathological stage no. (%) juvant Chemoradiotherapy (COREAN) study10
I 231 (33) 107 (31) involving 340 patients with cancer of the mid-
II 180 (26) 91 (26) dle or lower rectum who had received preopera-
III 233 (33) 125 (36) tive chemoradiotherapy, rates of locoregional
IV 4 (1) 0 recurrence were 2.6% after laparoscopic sur-
Missing data 18 (3) 3 (1) gery and 4.9% after open surgery. The presence
Macroscopic completeness of resec- of involved circumferential resection margins
tion no. (%) in the COREAN trial (2.9% after laparoscopic
Complete 589 (84) 303 (88) surgery and 4.1% after open surgery) were
Partially complete 58 (8) 19 (6) lower than those in our study.20 However, we
Incomplete 19 (3) 9 (3) considered circumferential resection margins
Missing data 33 (5) 14 (4) as being involved when tumor cells were pres-
Lymph nodes harvested
ent within 2 mm from the lateral surface of the
Median no. (IQR) 13 (1018) 14 (1019)
mesorectum, whereas the COREAN study group
Missing data no. (%) 16 (2) 4 (1)
used a 1-mm margin. The use of a 2-mm mar-
* Plusminus values are means SD. There were no significant differences be- gin yields a higher rate of involved circumfer-
tween the groups. Percentages may not total 100 because of rounding. IQR ential resection margins.16
denotes interquartile range. In our study, laparoscopic surgery in patients
The body-mass index is the weight in kilograms divided by the square of the
height in meters. with cancer in the lower third of the rectum was
The denominator is the number of patients who received preoperative radio- associated with a lower rate of involved circum-
therapy. ferential resection margin and a lower locore-
The patients with no residual tumor were not included in the analysis of patho-
logical stage. gional recurrence rate than was open surgery.
During laparoscopic surgery, narrow spaces such

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Laparoscopic vs. Open Surgery for Rectal Cancer

Table 2. Involved Circumferential Resection Margin and Locoregional Recurrence.

Involved Circumferential Resection Locoregional Recurrence in Locoregional Recurrence


Type of Lesion and Surgery Margin* Intention-to-Treat Population in As-Treated Population
Patients with Between-Group Between-Group Between-Group
Finding Difference Rate Difference Rate Difference
percentage points percentage points percentage points
no./total no. (%) (95% CI) % (90% CI) % (90% CI)
All lesions
Laparoscopic surgery 56/588 (10) 0.5 (4.9 to 3.5) 5.0 0.0 (2.6 to 2.6) 4.3 2.0 (4.7 to 0.7)
Open surgery 30/300 (10) 5.0 6.3
Upper rectal lesion
Laparoscopic surgery 18/196 (9) 0.1 (8.2 to 6.4) 3.5 0.6 (2.9 to 4.1) 3.0 0.9 (4.6 to 2.8)
Open surgery 9/97 (9) 2.9 3.9
Middle rectal lesion
Laparoscopic surgery 22/228 (10) 6.2 (0.1 to 11.2) 6.5 4.1 (0.7 to 7.5) 5.7 1.6 (2.3 to 5.5)
Open surgery 4/115 (3) 2.4 4.1
Lower rectal lesion
Laparoscopic surgery 15/164 (9) 12.4 (23.2 to 3.0) 4.4 7.3 (13.9 to 0.7) 3.8 8.9 (15.6 to 2.2)
Open surgery 17/79 (22) 11.7 12.7

* An involved circumferential resection margin was defined as the presence of tumor cells within 2 mm of the lateral surface of the mesorec-
tum. This finding is a risk factor for locoregional recurrence (i.e., recurrence in the pelvic or perineal area).
The denominator for the percentage calculation in this category was the number of patients without complete remission.
Between-group differences were calculated by subtracting the percentage of patients with the finding in the open-surgery group from the
percentage in the laparoscopic-surgery group.

as the lower pelvis are better visualized than in after laparoscopic surgery and 52.0% after open
open surgery owing to the use of a laparoscope, surgery. A similar finding was reported by Lacy
which projects a magnified and well-illuminated and colleagues15 among patients who underwent
image of the operative field on the monitors. A laparoscopic resection of lymph-nodepositive
clear view is of paramount importance to accom- colon cancers. These observations may confirm
plish a resection of the cancer with sufficient the experimental findings that less surgical
margins. As a result of tapering of the mesorec- trauma associated with the use of laparoscopic
tum at the level of the pelvic floor, tissue mar- techniques reduces tumor recurrence.23 In a
gins around low rectal cancers are smaller than study involving patients undergoing laparo-
those around tumors located in the middle or scopic and open colonic resection, laparoscopic
upper rectum, which predisposes such tumors surgery was followed by attenuated stress re-
to incomplete radical resection.21 Therefore, a sponses and improved preservation of immune
procedure called extralevatory abdominoperineal function.24 Further studies are necessary to deter-
rectum extirpation (ELAPE), in which a part of mine whether laparoscopic surgery for cancer is
the pelvic floor musculature is resected through associated with improved survival.
a perineal approach, has been introduced. Dur- The size of the cohort in our study allowed
ing the past decade, the ELAPE principle was for the use of a noninferiority margin of 5 per-
introduced but was not included in the COLOR centage points, whereas in the smaller COREAN
II study protocol.22 However, the debate on the trial, the noninferiority margin was 15 percent-
value of this technique continues. age points.20 Since centers in eight countries in
The disease-free survival rates at 3 years in Europe, North America, and Asia participated in
our study were 74.8% after laparoscopic surgery our study, the outcomes appear to be applicable
and 70.8% after open surgery, as compared with to surgical practice in general.
rates of 79.2% and 72.5%, respectively, during Rectal-cancer surgery, regardless of which
the same follow-up period in the COREAN technique is used, is technically demanding and
study.10 In our study, among patients with stage requires sufficient training to be performed
III disease, disease-free survival rates were 64.9% safely. We verified the surgical quality of laparo-

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A All Stages B Stage I


100 100
Open surgery
Laparoscopic surgery
90 90
80 80
Laparoscopic surgery

Disease-free Survival (%)

Disease-free Survival (%)


70 70
60 60
Open surgery
50 50
40 40
30 30
20 20
10 10
0 0
0 1 2 3 0 1 2 3
Years Years
No. at Risk No. at Risk
Laparoscopic 692 604 536 441 Laparoscopic 247 227 210 169
surgery surgery
Open surgery 344 297 264 211 Open surgery 117 114 106 85

C Stage II D Stage III


100 100
Laparoscopic surgery
90 90
80 80
Disease-free Survival (%)

Disease-free Survival (%)


Laparoscopic surgery
70 70
60 60
Open surgery
50 50 Open surgery
40 40
30 30
20 20
10 10
0 0
0 1 2 3 0 1 2 3
Years Years
No. at Risk No. at Risk
Laparoscopic 187 170 150 126 Laparoscopic 230 181 151 129
surgery surgery
Open surgery 92 80 74 61 Open surgery 124 93 75 57

Figure 2. Disease-free Survival, According to Disease Stage.

scopic total mesorectal excision by reviewing The conversion rate in our study remained 16%
unedited recordings of five consecutive laparo- throughout the study period, whereas a decline
scopic procedures for each center. Laparoscopic in the conversion rate from 38% in the first year
surgical expertise is difficult to measure objec- to 16% in the last year of the trial was reported
tively but is reflected to a certain extent by by the CLASICC group.19
operative time and conversion rate.25 The medi- In our study, patients with T4 and T3 lesions
an operating times for laparoscopic procedures within 2 mm of the endopelvic fascia were ex-
were 240 minutes in our study and 245 minutes cluded because laparoscopic resection of these
in the COREAN trial; the latter obviously was large tumors is very difficult and could result in
recorded by highly skilled surgeons, given the less-than-complete resection with subsequent
low conversion rate of only 1% in that study.20 higher rates of locoregional recurrence. There-

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Laparoscopic vs. Open Surgery for Rectal Cancer

A All Stages B Stage I


Laparoscopic surgery Open surgery
100 100
90 90
80 80 Laparoscopic surgery
Open surgery
Overall Survival (%)

Overall Survival (%)


70 70
60 60
50 50
40 40
30 30
20 20
10 10
0 0
0 1 2 3 0 1 2 3
Years Years
No. at Risk No. at Risk
Laparoscopic 692 659 612 511 Laparoscopic 247 240 230 191
surgery surgery
Open surgery 344 322 304 247 Open surgery 117 114 112 90

C Stage II D Stage III


100 Open surgery 100
90 90 Laparoscopic surgery
Laparoscopic surgery
80 80
Overall Survival (%)

Overall Survival (%)

70 70 Open surgery
60 60
50 50
40 40
30 30
20 20
10 10
0 0
0 1 2 3 0 1 2 3
Years Years
No. at Risk No. at Risk
Laparoscopic 187 179 167 143 Laparoscopic 230 213 189 160
surgery surgery
Open surgery 92 88 85 73 Open surgery 124 109 97 75

Figure 3. Overall Survival, According to Disease Stage.

fore, we do not recommend laparoscopic surgery pelvis and calibrate the measurements centrally
in patients with T4 or T3 rectal cancers with by independent professionals.
threatened circumferential margins. Some surgeons insert one of their hands
A limitation of our study is the absence of through a gastight port in the abdomen during
centralized macroscopic and microscopic evalu- laparoscopic colorectal surgery to allow for
ation of the resected specimens. However, all manual retraction of tissues and tactile feed-
pathologists adhered to a detailed standardized back, a procedure called hand-assisted laparo-
protocol. Another limitation is the use of dif- scopic surgery.26 The group who designed the
ferent imaging methods to determine the loca- study thought that a hand would obstruct the
tion of the tumor. It would have been preferable laparoscopic view of the narrow pelvis, so this
to standardize the imaging technique of the technique was not part of the current protocol.

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Laparoscopic vs. Open Surgery for Rectal Cancer

In conclusion, long-term outcomes of the search and education of doctors, Sahlgrenska University Hos-
pital, Gothenburg, Sweden; the Departments of Surgery and
COLOR II trial indicate that laparoscopic sur- Biostatistics, Erasmus University Medical Center, Rotterdam,
gery is as safe and effective as open surgery in the Netherlands; the Department of Surgery, Dalhousie Uni-
patients with rectal cancers without invasion of versity, Halifax, NS, Canada; and the Department of Surgery,
VU University Medical Center, Amsterdam.
adjacent tissues. Disclosure forms provided by the authors are available with
Supported by Ethicon Endo-Surgery Europe; grants from the the full text of this article at NEJM.org.
Swedish Cancer Society (2010/593 and 2013/497); the Health We thank Karen Inglis and Kevin Druhan of Dalhousie
and Medical Care Committee of the Regional Executive Board, University for coordinating the trial and gathering and pro-
Region Vstra Gtaland, and an agreement concerning re- cessing data.

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