Randomized clinical trial

Five-year follow-up of the Medical Research Council CLASICC

trial of laparoscopically assisted versus open surgery for
colorectal cancer
D. G. Jayne1 , H. C. Thorpe3 , J. Copeland3 , P. Quirke2 , J. M. Brown3 and P. J. Guillou1
1
Section of Translational Anaesthesia and Surgery and 2 Department of Pathology, Leeds Institute of Molecular Medicine, St Jamess University Hospital,
and 3 Clinical Trials Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
Correspondence to: Mr D. G. Jayne, Section of Translational Anaesthesia and Surgery, Level 7 Clinical Sciences Building, St Jamess University Hospital,
Leeds LS9 7TF, UK (e-mail: David.Jayne@leedsth.nhs.uk)

Introduction: The UK Medical Research Council CLASICC trial assessed the safety and efficacy of
laparoscopically assisted surgery in comparison with open surgery for colorectal cancer. The results of
the 5-year follow-up analysis are presented.
Methods: Five-year outcomes were analysed and included overall and disease-free survival, and local,
distant and wound/port-site recurrences. Two exploratory analyses were performed to evaluate the effect
of age (70 years or less, or more than 70 years) on overall survival between the two groups, and the effect
of the learning curve.
Results: No differences were found between laparoscopically assisted and open surgery in terms of
overall survival, disease-free survival, and local and distant recurrence. Wound/port-site recurrence rates
in the laparoscopic arm remained stable at 24 per cent. Conversion to open operation was associated
with significantly worse overall but not disease-free survival, which was most marked in the early followup period. The effect of surgery did not differ between the age groups, and surgical experience did not
impact on the 5-year results.
Conclusion: The 5-year analyses confirm the oncological safety of laparoscopic surgery for both
colonic and rectal cancer. The use of laparoscopic surgery to maximize short-term outcomes
does not compromise the long-term oncological results. Registration number: ISRCTN74883561
(http://www.controlled-trials.com).

Presented to the National Cancer Research Institute Cancer Conference, Birmingham, UK, October 2007
Paper accepted 27 April 2010
Published online 13 July 2010 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.7160

Introduction

The Medical Research Council Conventional versus

Laparoscopic-Assisted Surgery In Colorectal Cancer
(MRC CLASICC) trial was set up in 1996 to evaluate
the technical and oncological safety and efcacy of laparoscopically assisted surgery in comparison with conventional
open surgery for the treatment of colorectal cancer. Similar studies, originating in the USA1 , the Netherlands2
and Singapore3 , were commenced around the same time.
Unique to the CLASICC trial was the inclusion of rectal cancers together with the standardized reporting and
centralized review of pathological resection specimens.
The short-term results from these trials were published
around 20042005 and, although perhaps not realizing
2010 British Journal of Surgery Society Ltd
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the full potential of the laparoscopic approach, they were

viewed positively and were instrumental in bringing about
its wider implementation. In the UK, the National Institute for Health and Clinical Excellence modied its initial
guidance, issued in 20004 , which recommended that for
colorectal cancer, open rather than laparoscopic resection
should be the preferred surgical procedure, to an updated
recommendation in 20065 , which stated laparoscopic
resection is recommended as an alternative to open resection in individuals with colorectal cancer in whom both
laparoscopic and open surgery are considered suitable.
Although laparoscopic surgery for colonic cancer is
now practised widely, with proven short-term benets
for patient recovery, the case for laparoscopic rectal cancer
surgery remains more controversial. A body of opinion,
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Five-year follow-up of MRC CLASICC trial

albeit probably in a diminishing minority, still expresses

concern regarding its oncological efcacy. Critical analysis
is hindered by a relative lack of good quality data, and even
today the CLASICC trial remains the only multicentre randomized study. The early results from CLASICC did little
to allay concerns, with higher but non-signicant rates of
circumferential resection margin (CRM) involvement6 and
a trend to worse male sexual function7 following laparoscopic anterior resection. However, at 3-year follow-up the
difference in CRM positivity had not translated into a difference in local recurrence rates between open and laparoscopic techniques8 , although further follow-up was deemed
necessary before a denite conclusion could be reached.
This article presents the 5-year follow-up data from
the CLASICC trial, including analyses of the secondary
endpoints of overall and disease-free survival, and local,
distant and wound/port-site recurrence for both colonic
and rectal cancers.
Methods

The design of the MRC CLASICC trial, together with its

short-term outcomes and 3-year follow-up data, has been
reported previously8,9 . In total, 794 patients were recruited
from 27 UK centres and 32 surgeons between July 1996
and July 2002; 413 patients had colonic cancer and 381 had
rectal cancer. Patients were randomized on a 2 : 1 basis in
favour of laparoscopic surgery, such that 526 were assigned
to the laparoscopic arm and 268 to the open surgery arm.
The present study investigated the 5-year outcomes, and
included the secondary endpoints of 5-year overall survival (OS), disease-free survival (DFS), and locoregional,
wound/port-site and distant recurrences.
OS was calculated from the date of randomization to the
date of death from any cause. Patients alive or lost to followup were censored at the date last known to be alive. DFS
was calculated from the date of randomization to the date of
recurrence or death (from any cause) for patients who had
curative surgery. Patients alive without recurrent disease
or lost to follow-up were censored at the date last known
to be alive and recurrence free. Time to local, distant or
wound/port-site recurrence was calculated from the date of
randomization to the date of recurrence for those who had
curative surgery. Patients without evidence of recurrence
at death were censored at the date of death. Follow-up
after 5 years of randomization was censored in all analyses.
Differences in survival and recurrences between groups
were compared using KaplanMeier curves and tested with
log rank and Wilcoxon rank sum tests. Cox proportional
hazards regression models were used to adjust for the
stratication factors used in the randomization (tumour
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1639

site, presence of liver metastases, preoperative radiotherapy and surgeon) and other prognostic factors (age, sex
and Dukes stage). Sensitivity analyses were performed to
assess the impact of exclusions for DFS on OS. Sensitivity
analyses were also performed to assess the effect of conversions (from laparoscopic to open surgery) on the results.
As sensitivity analyses or adjustment for sex, age, Dukes
stage and stratication factors made little difference to
conclusions, differences between treatment estimates are
presented from unadjusted analyses.
Two additional exploratory analyses were performed.
The rst investigated the effect of surgery on OS for
patients who were aged 70 years or less at the time of randomization and for those who were over 70 years old. The
second analysed only those patients recruited by surgeons
who randomized more than 20 patients. In this analysis,
patients were categorized into two groups, the rst and
last half of randomized cases per surgeon, and the effect of
surgery on OS was examined in these separate groups to
investigate whether the experience gained during the trial
had an impact on the results.
All hypothesis tests were at the 1 per cent signicance
level (two-sided) for the 5-year endpoints and were performed using the intention-to-treat and actual treatment
populations (analysed according to treatment actually
received: open, laparoscopic or laparoscopic converted
to open surgery). All statistical analyses were performed
using SAS version 9.1 (SAS Institute, Cary, North Carolina, USA).
Results

A CONSORT diagram depicting the allocation of patients

within the 5-year follow-up analysis is presented in Fig. 1.
At the time of analysis, median follow-up of all patients
was 563 (interquartile range (i.q.r.) 223773) months.
Median follow-up for those patients still alive was 698
(i.q.r. 575922) months.
Data were unavailable for analysis of OS survival in 59
patients (17 laparoscopic, 42 open), and for analysis of DFS
in 50 patients (15 laparoscopic, 35 open).

Overall survival
The 5-year OS rate for all patients was 579 (95 per cent
condence interval (c.i.) 544 to 615) per cent, with 109
deaths in the open arm and 213 in the laparoscopic arm.
Overall cause of death was similar in the two arms. There
was no difference in the 5-year OS rate between the
two groups (581 per cent for open versus 579 per cent for
laparoscopic surgery; difference 02 (95 per cent c.i. 76
to 73) per cent; log rank statistic = 0037, P = 0848).
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D. G. Jayne, H. C. Thorpe, J. Copeland, P. Quirke, J. M. Brown and P. J. Guillou

Allocated to laparoscopically assisted surgery n = 526

Received laparoscopically assisted surgery n = 483
Received open surgery n = 24
Received transanal endoscopic microsurgery n = 1
Missing data on received surgery n = 14
Did not receive surgery n = 4
Died before surgery n = 1
Not well enough to have general anaesthetic n = 1
Received polypectomy only n = 1
Missing data on reason for no surgery n = 1
Converted from laparoscopically assisted to open
surgery during operation n = 144

Follow-up

Patients with less than 5 years of follow-up n = 41

Less than 1 year of follow-up n = 1
12 years of follow-up n = 2
23 years of follow-up n = 4
34 years of follow-up n = 10
45 years of follow-up n = 24

Patients with less than 5 years of follow-up n = 76

Less than 1 year of follow-up n = 4
12 years of follow-up n = 3
23 years of follow-up n = 3
34 years of follow-up n = 32
45 years of follow-up n = 34

Analysed (OS) n = 268

Analysed (DFS) n = 212
Excluded from DFS analysis n = 56
No surgery n = 2
Unresectable tumour n = 8
Metastatic disease at surgery n = 38
Non-malignant tumour n = 14

Analysed (OS) n = 526

Analysed (DFS) n = 429
Excluded from DFS analysis n = 97
No surgery n = 4
Unresectable tumour n = 7
Metastatic disease at surgery n = 66
Non-malignant tumour n = 28

Allocation

Allocated to open surgery n = 268

Received open surgery n = 256
Received laparoscopically assisted surgery n = 4
Missing data on received surgery n = 6
Did not receive surgery n = 2
Stented owing to liver metastases n = 1
Missing data on reason for no surgery n = 1

Analysis

Enrolment

Patients randomized n = 794

CONSORT diagram depicting allocation of patients in 5-year follow-up analysis. OS, overall survival; DFS, disease-free survival.
*Patients not known to have died and whose last follow-up information was less than 5 years from randomization. Also time to local,
distant and wound/port-site recurrence. More than one reason may be given per patient

Fig. 1

The 5-year OS rate for patients with colonic and rectal

cancer was 581 (95 per cent c.i. 532 to 630) per cent
and 578 (527 to 629) per cent respectively. There was
no difference in OS for patients with colonic or rectal
cancer with respect to the randomized procedure. For
colonic cancer, the 5-year OS rate was 627 per cent
for open versus 557 per cent for laparoscopic surgery
(difference 70 (95 per cent c.i. 172 to 32) per cent;
log rank statistic = 1306, P = 0253). For rectal cancer,
the 5-year OS rate was 529 per cent for open versus
603 per cent for laparoscopic surgery (difference 74
(95 per cent c.i. 34 to 183) per cent; log rank statistic =
2265, P = 0132).
No difference in OS was seen between the two techniques for patients with rectal cancer undergoing either
anterior resection or abdominoperineal resection. For
anterior resection, the 5-year OS rate was 567 per cent
for open versus 628 per cent for laparoscopic surgery (difference 60 (95 per cent c.i. 64 to 185) per cent; log

rank statistic = 1339, P = 0247). For abdominoperineal

resection, the 5-year OS rate was 418 per cent for open
versus 532 per cent for laparoscopic surgery (difference
114 (95 per cent c.i. 103 to 331) per cent; log rank
statistic = 1033, P = 0310).
Overall, there was no difference between the two techniques for any stage of disease. The non-signicant trend
for improved OS following laparoscopic surgery in patients
with Dukes A rectal cancer, previously reported for the 3year follow-up, did not persist at 5 years (log rank statistic
= 0474, P = 0491).
OS for patients who had conversion to open surgery
was signicantly worse (open 585 per cent, laparoscopic
624 per cent, conversion 496 per cent; log rank statistic
= 10615, P = 0005), and this difference was maintained
between actual treatment groups even after adjustment
for the stratication factors of sex, age and Dukes stage
(P = 0003). Sensitivity analysis of the survival data only
for surgeons with a lower than average conversion rate

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Proportion surviving

Five-year follow-up of MRC CLASICC trial

10
09
08
07
06
05
04
03
02
01
0

1641

Open
Laparoscopic
Conversion
6

12

18

24

30

36

42

48

54

60

145 137 126 119 111 106 98 91 78

227 216 205 196 187 167 140 132 119
46 43 38 34 33 31 30 26 25

65
98
22

Time from randomization (months)

No. at risk
Open
158
Laparoscopic 243
Conversion
57

Five-year overall survival by actual procedure for all

patients randomized by surgeons with a lower than average
conversion rate. P = 0033 (log rank test); P = 0013
(Wilcoxon test)

Fig. 2

showed that the survival of converted patients remained

considerably lower, indicating that a surgeon-related factor was unlikely to be involved (log rank statistic = 6828,
P = 0033) (Fig. 2).

Disease-free survival
A total of 641 patients (212 randomized to open and 429
to laparoscopic surgery, 315 with colonic and 326 with
rectal cancer) were eligible to be included in the DFS
analyses, and time to local, wound/port-site and distant
recurrence analyses.
The 5-year DFS rate for all patients was 564 (95 per cent
c.i. 524 to 603) per cent, with no difference between
the two surgical techniques: 586 per cent for open versus 553 per cent for laparoscopic surgery (difference 34
(95 per cent c.i. 118 to 50) per cent; log rank statistic =
0492, P = 0483). DFS for patients with colonic and rectal
cancer was 600 (95 per cent c.i. 544 to 656) per cent and
529 (473 to 585) per cent respectively.
There was no difference in DFS for patients with either
colonic or rectal cancer with respect to the randomized
procedure. For colonic cancer, the 5-year DFS rate was
640 per cent for open versus 576 per cent for laparoscopic
surgery (difference 64 (95 per cent c.i. 179 to 52)
per cent; log rank statistic = 0712, P = 0399). For rectal
cancer, the 5-year DFS rate was 521 per cent for open versus 532 per cent for laparoscopic surgery (difference 11
(95 per cent c.i. 112 to 134) per cent; log rank statistic
= 0004, P = 0953).
Overall, there was no difference between the two techniques for any stage of colonic or rectal cancer. The
non-signicant trend for improved DFS after laparoscopic
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surgery in patients with Dukes A rectal cancers, previously

reported at the 3-year follow-up, did not persist at 5 years
(log rank statistic = 0264, P = 0607).
There was no difference in the 5-year DFS rate between
the two techniques for patients with rectal cancer undergoing either anterior resection (576 per cent for open
versus 577 per cent for laparoscopic surgery; difference
005 (95 per cent c.i. 142 to 143) per cent; log rank statistic = 0045, P = 0832) or abdominoperineal resection
(362 per cent for open versus 414 per cent for laparoscopic surgery; difference 52 (95 per cent c.i. 177 to
281) per cent; log rank statistic = 0249, P = 0618).
Unlike OS, 5-year DFS for converted patients was not
signicantly worse (using a 1 per cent signicance level),
although a trend for worse outcome was noted even when
adjusting for the stratication factors of sex, age and Dukes
stage (P = 0030).

Local recurrences
The overall local recurrence rate at 5 years was 101
(95 per cent c.i. 75 to 127) per cent, with no difference between the two procedures (87 per cent for open
versus 108 per cent for laparoscopic surgery; difference
21 (95 per cent c.i. 73 to 32) per cent; log rank
statistic = 0285, P = 0594). In patients with rectal cancer, local recurrence rates following anterior resection and
abdominoperineal resection were 89 (95 per cent c.i. 49
to 128) per cent and 177 (84 to 269) per cent respectively, giving a difference in the 5-year local recurrence rate
of 88 (95 per cent c.i. 13 to 188) per cent. In patients
undergoing anterior resection, the previously reported differences in CRM positivity rates did not translate into a
difference in the 5-year local recurrence rate: 76 per cent
for open versus 94 per cent for laparoscopic surgery (difference 18 (95 per cent c.i. 99 to 63) per cent; log
rank statistic = 0110, P = 0740). Similarly, there was no
difference in local recurrence rates between the two techniques in patients undergoing abdominoperineal resection
(data not shown).

Distant recurrences
Some 111 distant recurrences were recorded within 5 years
of randomization, giving an overall distant recurrence
rate of 209 (95 per cent c.i. 174 to 244) per cent. No
difference was observed between the two surgical techniques: distant recurrence rate of 206 per cent for open
versus 210 per cent for laparoscopic surgery (difference
04 (95 per cent c.i. 78 to 71) per cent; log rank
statistic = 0052, P = 0820). There was no difference
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D. G. Jayne, H. C. Thorpe, J. Copeland, P. Quirke, J. M. Brown and P. J. Guillou

in distant recurrence rates in patients with rectal cancer undergoing either anterior resection (219 per cent for
open versus 219 per cent for laparoscopic surgery; difference 002 (95 per cent c.i. 128 to 129) per cent; log
rank statistic = 0027, P = 0869) or abdominoperineal
resection (408 per cent for open versus 357 per cent for
laparoscopic surgery; difference 51 (210 to 313) per
cent; log rank statistic = 0092, P = 0762).
The 5-year distant recurrence rate for patients converted
from laparoscopic to open operation was not signicantly
worse even after adjustment for the stratication factors of
sex, age and Dukes stage (P = 0679).

Wound/port-site recurrences
No further port-site recurrences were reported between
3 and 5 years after randomization. Overall, there was
one wound/port-site recurrence in the open arm and
nine in the laparoscopic arm (laparoscopic wound/portsite recurrence rate 24 per cent), of which only one
was highlighted as being a true port-site rather than an
extraction-site recurrence.

Exploratory analyses
In the exploratory analysis for age, 410 patients were
aged 70 years or less at the time of randomization, with
134 assigned to open and 276 to laparoscopic surgery.
There was no difference in the 5-year OS rate for the two
techniques: 650 per cent for open versus 677 per cent for
laparoscopic surgery (difference 27 (95 per cent c.i. 73
to 126) per cent; log rank statistic = 0364, P = 0547).
Similarly, there was no difference in the 384 patients older
than 70 years: 510 per cent of 134 patients having open
versus 470 per cent of 250 patients undergoing laparoscopic surgery (difference 40 (149 to 69) per cent; log
rank statistic = 0171, P = 0679).
In the exploratory analysis that looked at experience
gained within the trial, and which included only those
patients recruited by surgeons who randomized more than
20 patients, 326 patients constituted the rst half and
331 the second half of patients recruited. There was no
difference in 5-year OS between the open and laparoscopic
arms for either group of patients.
Discussion

The short-term and 3-year follow-up data from the

MRC CLASICC trial have been reported previously8 and
together with other multicentre randomized trials1 3 and
meta-analyses10 12 have helped to establish laparoscopic
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surgery as a recognized option for colonic cancer and

probably also for rectal cancer. The 5-year analysis has not
demonstrated any difference in OS or DFS for patients
with colonic or rectal cancer treated by laparoscopic as
compared to open surgery.
Although there is a growing enthusiasm for laparoscopic
rectal cancer surgery, it is still not universally accepted
and concerns persist regarding the adequacy of oncological
resection. To some extent, these concerns were supported
by the short-term pathological outcomes of the CLASICC
trial, which reported a non-signicant increased rate in
CRM positivity in patients undergoing laparoscopic anterior resection: 63 per cent for open versus 124 per cent
for laparoscopic surgery (difference 61 (95 per cent c.i.
21 to 144) per cent)9 . This difference, however, did not
translate into a difference in local recurrence at the 3-year
follow-up8 .
The present analysis conrms that there is still no
difference in local recurrence rates following laparoscopic
compared with open rectal cancer surgery on the longer
5-year follow-up. This will be reassuring to those
surgeons performing the technique and should help to
promote laparoscopic rectal cancer surgery such that
the recognized short-term benets become available to
the majority of patients. There remains a disparity in
the local recurrence rate between patients treated by
anterior resection and those undergoing abdominoperineal
resection, with an 88 per cent increased risk for the latter.
This difference in local recurrence relating to anatomical
position of the cancer is well recognized, and it is
hoped that recent developments with the introduction
of cylindrical abdominoperineal resection will go at least
some way to rectifying the situation13 . The ability to
perform a cylindrical abdominoperineal resection is in
no way hindered by a laparoscopic approach, and any
improved oncological outcomes should be equally realized
irrespective of the abdominal approach to the resection.
Although many of the ndings reported here showed
no difference between the laparoscopic and open arms,
this was not unexpected and should be viewed positively
in terms of the advancement of laparoscopic surgery.
Overall, no signicant difference was observed in OS
or DFS with stage of disease. This is contrary to the
ndings previously reported by Lacy and colleagues14 in
their single-institution study, where a survival advantage
was apparent following laparoscopic versus open colectomy
for stage III (Dukes C) colonic cancer. The pitfalls of
subgroup analyses are well recognized, as demonstrated
by the suggestion of an improved OS and DFS following
laparoscopic resection of Dukes A rectal cancer reported
in the 3-year CLASICC data. This has not persisted on
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5-year follow-up and can therefore be reasonably dismissed

as a statistical phenomenon.
Recent data from Hohenberger and co-workers15 and
others16 18 have suggested that a more radical segmental
resection, with high vascular ligation and complete regional
lymphadenectomy, can result in improved cancer-specic
outcomes. There is no evidence within the CLASICC
trial to suggest that laparoscopic colectomy results in a
lesser oncological resection, as determined by pathological
resection margins and lymph node yields. However, it
remains important that, whilst attempts are made to
reduce the surgical morbidity by the adoption of minimally
invasive techniques, this should not be at the expense
of a compromised oncological resection. Whether a high
vascular ligation and complete regional lymphadenectomy,
as described by Hohenberger et al.15 and advocated by the
Japanese Society for Cancer of the Colon and Rectum19
can be achieved safely by laparoscopic means18 20 , and
indeed whether it is justied in all cases, remains to be
determined21 .
One of the criticisms levelled at the CLASICC trial was
that it was conducted on the learning curve, as evidenced
by the high conversion rates for laparoscopic colonic
(25 per cent) and, in particular, for laparoscopic rectal
(34 per cent) cancer surgery9 . Although the trial design
attempted to mitigate against this, with a prerequisite
that every surgeon complete at least prior 20 laparoscopic
procedures, it is accepted that some surgeons were
probably still learning the technique during recruitment.
Although this may have contributed to the high conversion
rates, it is unlikely to have had a signicant inuence
on the survival outcomes as demonstrated by the
exploratory analysis of surgeon experience within the
trial. It is now known that conversion rates in the
order of 510 per cent can be achieved by experienced
laparoscopic surgeons. This should not detract from the
impact of CLASICC, but rather it might be considered
a strength of the study. Unlike the single-institution
series reported by experienced laparoscopic surgeons,
CLASICC was a pragmatic, multicentre study and as
such is more likely to represent the real-life situation
at that time. Indeed, the high conversion rates are likely
to have had a positive effect, demonstrating to those
less experienced surgeons that appropriate conversion was
not a sign of surgical failure but rather an acceptable
strategy in unfavourable circumstances. In addition,
it is unlikely that the high conversion rate was all
attributable to a learning curve effect. Advances in surgical
technique and technological advances in instrumentation
evolved during the course of and after the trial, and

undoubtedly these contributed to the lower conversion

rates reported here.
The issue of conversion and its effect on morbidity
and mortality remains controversial. Some studies have
suggested that conversion does not inuence outcome22,23 ,
but others24,25 support the 5-year follow-up analysis
presented here, which demonstrates a clear survival
disadvantage associated with conversion. It is interesting
that the sensitivity analysis of the survival data for surgeons
with a lower than average conversion rate showed the same
decreased survival as for the group as a whole, suggesting
that the worse outcome in converted patients was not
attributable to a surgeon-related factor. Thus, it would
appear that conversion has a deleterious effect regardless
of the experience of the surgeon. Although advanced
cancer pathology was cited as the most common reason
for conversion in both colonic and rectal cancer26 , this is
unlikely to be the full explanation given that divergence in
the survival curves occurred within the rst 30 days after
surgery and thereafter remained relatively constant. In
addition, the adverse impact of conversion was signicant
only for OS and not for DFS. Thus, conversion for
other reasons (obesity, technical difculties, complications,
etc.) appears to have a bad outcome independent of
surgical experience.
The other exploratory analysis examined the effect of
age on outcomes following laparoscopic resection. Several
studies have reported improved short-term benets of a
laparoscopic approach in the elderly27 29 . The present
study showed no difference in OS between the two surgical
techniques in patients aged 70 years or less and those older
than 70 years. Thus, the benets of a laparoscopic approach
in the elderly appear to be in short-term gains rather than
long-term outcomes.
Although the CLASICC trial has succeeded in its aim to
evaluate the efcacy and safety of laparoscopic colorectal
cancer surgery, there are lessons to be learnt from it
about the conduct of large multicentre trials of surgical
technique. It is a tribute to the participating surgeons that
a total of 794 patients were recruited, but the accrual was
slower than anticipated, extending over a 6-year period.
Surgical technique and technology will continue to evolve
during the course of any trial and it is imperative that
evaluation proceeds in a timely fashion, ensuring that the
results remain contemporary.

2010 British Journal of Surgery Society Ltd

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Acknowledgements

The MRC CLASICC trial was funded by the UK

Medical Research Council. The authors declare no conict
of interest.
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D. G. Jayne, H. C. Thorpe, J. Copeland, P. Quirke, J. M. Brown and P. J. Guillou

Collaborators

The 5-year follow-up analysis is presented on behalf of the

CLASICC trial collaborators who include:
M. Stead, E. Graham, S. Bell, V. Hiley, Z. Bennett,
R. Heath, A. Smith, the Trial Steering Committee (A. G.
Johnson, N. Bosanquet, P. J. Franks, J. R. T. Monson), the
Data Monitoring and Ethics Committee (Z. H. Krukowski,
G. D. Oates, R. Stephens, M. Sculpher) and the following
institutions, surgeons and local pathologists.
Surgeons: R. Kapadia, R. Khan (Airedale General
Hospital, Keighley, UK); R. Foley (Bedford General
Hospital, Bedford, UK); M. Thomas (Bristol Royal
Inrmary, Bristol, UK); J. Monson, G. Duthie (Castle
Hill Hospital, Hull, UK); R. Motson (Colchester General
Hospital, Colchester, UK); M. Parker (Darent Valley
Hospital, Dartford, UK); D. Bartolo (Edinburgh Royal
Inrmary, Edinburgh, UK); A. Horgan (Freeman Hospital,
Newcastle, UK); P. Sagar (Leeds General Inrmary, Leeds,
UK); W. Barrie (Leicester General Hospital, Leicester,
UK); R. Swift (Mayday University Hospital, Thornton
Heath, UK); H. Wegstapel (Medway Maritime Hospital,
Gillingham, UK); K. Campbell (Ninewells Hospital,
Dundee, UK); P. Haray (Prince Charles Hospital, Merthyr
Tydl, UK); M. Van den Bossche (Princess Elizabeth
Hospital, Guernsey, UK); J. Scholeeld (Queens Medical
Centre, Nottingham, UK); K. Vellacott (Royal Gwent
Hospital, Newport, UK); M. Hershman (Royal Liverpool
Hospital, Liverpool, UK); J. Tate (Royal United Hospital,
Bath, UK); J. Varma, H. Gallagher (Royal Victoria
Inrmary, Newcastle upon Tyne, UK); P. Guillou, A.
Windsor (St Jamess University Hospital, Leeds, UK);
H. Scott (St Peters Hospital, Chertsey, UK); G. Deans
(Stepping Hill Hospital, Stockport, UK); B. Rees, D. Carey
(University Hospital of Wales, Cardiff, UK); J. Wellwood
(Whipps Cross Hospital, Leytonstone, UK); N. Tafnder
(William Harvey Hospital, Ashford, UK); R. Kennedy
(Yeovil District General Hospital, Yeovil, UK).
Local pathologists: P. Da Costa, J. ODowd (Airedale
General Hospital, Keighley, UK); D Rimmer (Bedford
General Hospital, Bedford, UK); P. Conn (Colchester
General Hospital, Colchester, UK); P. Thebe (Darent
Valley Hospital, Dartford, UK); H. Gilmour (Edinburgh
Royal Inrmary, Edinburgh, UK); A. MacDonald (Hull
Royal Inrmary, Hull, UK); B. Warren (John Radcliffe
Inrmary, Oxford, UK); P. Quirke (Leeds General
Inrmary, Leeds, UK); E. Mackay (Leicester General
Hospital, Leicester, UK); A. Arnaout (Mayday University
Hospital, Thornton Heath, UK); R. Lindley (Medway
Maritime Hospital, Gillingham, UK); F. Carey (Ninewells
Hospital, Dundee, UK); S. Kiberu (Prince Charles
Hospital, Merthyr Tydl, UK); C. Chinyama (Princess
2010 British Journal of Surgery Society Ltd
Published by John Wiley & Sons Ltd

Elizabeth Hospital, Guernsey, UK); D. Jenkins (Queens

Medical Centre, Nottingham, UK); J. Nash (Royal
Liverpool Hospital, Liverpool, UK); N. Rooney (Royal
United Hospital, Bath, UK); J. Shrimankar (Royal Victoria
Inrmary, Newcastle upon Tyne, UK); N. Scott, J. Wyatt
(St Jamess University Hospital, Leeds, UK); N. Ratcliffe
(St Peters Hospital, Chertsey, UK); R. Hale (Stepping
Hill Hospital, Stockport, UK); G. Williams (University
Hospital of Wales, Cardiff, UK); A. Abdulkadir (William
Harvey Hospital, Ashford, UK); J. Shefeld (Yeovil District
General Hospital, Yeovil, UK).
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Published by John Wiley & Sons Ltd

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British Journal of Surgery 2010; 97: 16381645