Case Study 3. Establishing the effectiveness of laparoscopic surgery for colorectal cancer leading to safer implementation into the NHS and world-wide for greater a patient benefit
Submitting InstitutionUniversity of Leeds
Unit of AssessmentClinical Medicine
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis
Summary of the impact
The MRC Conventional versus Laparoscopic-Assisted Surgery In Colorectal
Cancer trial (CLASICC) is the largest and most successful UK trial of a
technology applied to general surgery. It addressed an area of huge
clinical uncertainty, providing a rigorous evaluation of a new technology
and enabling its safe and widespread implementation. The impact of CLASICC
has been global, confirming the advantages for patients (quicker recovery)
and healthcare providers (cost-effectiveness) and so influencing national
and international policy in favour of the laparoscopic technique. It
informed NICE guidance and led to a major DH initiative that has seen the
UK become one of the largest providers in the world of laparoscopic
colorectal cancer surgery. CLASICC is regarded as a benchmark surgical
trial, combining high quality trial design with rigorous quality
assurance, which has informed the design of many subsequent colorectal
The introduction of new technologies into surgical practice is seldom
based on rigorous scientific evaluation. Such was the case for
laparoscopic surgery in the 1980's. Although the potential benefits in
terms of improved patient recovery were not in dispute, concerns were
expressed regarding its safety, particularly in the treatment of malignant
disease with early reports of unusual patterns of disease recurrence.
The MRC CLASICC trial was set up in 1996 to specifically address concerns
regarding the safety and efficacy of the laparoscopic approach in
colorectal cancer. Led by Professor P.J.Guillou (Prof. of Surgery
— retired 2006), facilitated by Professor D.G.Jayne (Leeds/former
MRC Clinical Research Fellow), and coordinated by Professor
J.M.B.Brown (Director, Clinical Trials Research Unit, Leeds), this
University of Leeds initiated, UK-wide, multicentre clinical trial
recruited one of the largest cohorts of surgical patients (794 patients)
to either laparoscopic or conventional open colorectal cancer surgery
between 1996 and 2002.
The initial results, reported in the Lancet in 2005 (1), stimulated an
Editorial and much exchange of international correspondence. Laparoscopic
surgery was shown to be as safe as open surgery, but with short-term
benefits for patients, and similar oncological outcomes. CLASICC was
unique in the rigour of its trial design and quality control, combining
for the first time centralised pathological review and evaluation of the
quality of surgery (1, 2); a feature that has been widely adopted in the
design of subsequent clinical trials and has become standard in routine
NHS practice. The publication of the 3-year CLASICC results in 2007 (2),
and subsequently the 5-year results in 2010 (3), confirmed long-term
oncological safety and further reinforced positive world opinion towards
laparoscopic surgery. It is now internationally acknowledged that
laparoscopic surgery has benefits for patients without compromise to
long-term outcomes. Any previous criticisms towards the laparoscopic
approach have been dispelled, enabling its safe dissemination into routine
CLASICC was designed as a pragmatic trial, which has been instrumental in
enabling the translation of its results to the wider surgical community.
It was also comprehensive in its evaluation, which has enabled valuable
information to be gained about the broader benefits of the laparoscopic
approach. It has provided information on cost-effectiveness (4),
predictors of conversion to open surgery (5), sexual and bladder function
following rectal resection (6), and benefits of the laparoscopic approach
in the prevention of adhesive bowel obstruction and incisional herniation.
The outputs from CLASICC, showing improved cost-effectiveness and better
functional outcomes, have subsequently been confirmed by other studies.
Until 2013, CLASICC was the only randomised, multicentre trial to
evaluate the laparoscopic approach for rectal cancer and thus provided the
only randomised data to inform healthcare policy. It showed that the
laparoscopic approach was feasible and potentially beneficial in rectal
cancer surgery, and that with certain caveats it could be recommended for
routine application. The findings were endorsed in 2013 with the
publication of a large, multicentre European study (COLOR II).
CLASICC set the standard for evaluating new surgical techniques by
randomised comparison. As the foremost clinical trial in laparoscopic
colorectal cancer surgery, it set the benchmark in trial design for other
colorectal cancer studies around the world (NMRC-Singapore trial, European
COLOR II [L],US NIH ACOSOG-Z6051) [K]. International collaboration led to
a large transatlantic meta-analysis that revealed the biases present in
other smaller, single institution studies. The expertise gained from
CLASICC has been instrumental in developing follow-on research
initiatives, which include the MRC/EME/NIHR ROLARR trial; a pan-World
randomised controlled trial evaluating robotic-assisted with laparoscopic
surgery for rectal cancer.
References to the research
1) Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AHM,
Heath RM, Brown JM. Short-term endpoints of conventional versus
laparoscopic-assisted surgery in patients with colorectal cancer (MRC
CLASICC Trial): multicentre randomised controlled trial. The Lancet 2005;
Publication showing that laparoscopic surgery is as
effective as open surgery for the treatment of colorectal cancer. Unique
pathological assessment demonstrating high quality laparoscopic
2) Jayne DG, Guillou PJ, Thorpe H, Quirke P, Copeland J, Smith AHM,
Heath RM, and Brown JM. Randomized Trial of Laparoscopic-Assisted
Resection of Colorectal Carcinoma: 3-Year Results of the UK MRC CLASICC
Trial Group. J Clin Oncology 2007; 25: 3061-68.
Publication showing that the mid-term
results of laparoscopic surgery are at least as good as open surgery for
colorectal cancer. Concerns about higher local recurrence following
laparoscopic rectal cancer resection disproven.
3) Jayne DG, Thorpe HC, Copeland J, Quirke P, Brown JM, Guillou PJ.
Five year follow-up of the Medical Research Council CLASICC trial of
laparoscopically assisted versus open surgery for colorectal cancer. Br J
Surg. 2010; 97: 1638-45. doi:10.1002/bjs.7160.
that the use of laparoscopic surgery to maximise short-term outcomes for
colorectal cancer does not compromise long-term oncological results.
Conversion from laparoscopic to open surgery associated with worse
overall but not disease-free survival.
4) Franks PJ. Bosanquet N. Thorpe H. Brown JM. Copeland J. Smith AM.
Quirke P. Guillou PJ. CLASICC trial participants. Short-term costs
of conventional vs laparoscopic assisted surgery in patients with
colorectal cancer (MRC CLASICC trial). British Journal of Cancer.
95(1):6-12, 200. doi:10.1038/sj.bjc.6603203.
Publication documenting the short-term cost effectiveness of
laparoscopic surgery for colorectal cancer.
5) Thorpe H, Jayne DG, Guillou PJ, Quirke P, Copeland J, Brown JM.
Patient factors influencing conversion from laparoscopic assisted to open
surgery for colorectal cancer. Br J Surg. 2008; 95: 199-205. PMID:17696215
Publication identifying those patients most likely to benefit from
laparoscopic surgery for colorectal cancer. Establishes selection
criteria for the laparoscopic approach, helping to avoid unplanned
conversion to open surgery with documented worse overall survival
(established in , above).
6) Jayne DG, Brown JM, Thorpe H, Walker J, Quirke P,
Guillou PJ. Bladder and sexual function following resection for
rectal cancer in a randomized clinical trial of laparoscopic versus open
technique. Br J Surg. 2005; 92(9): 1124-32. PMID:15997446
Publication highlighting the need for high quality laparoscopic rectal
cancer surgery to minimise the risk of postoperative bladder and sexual
Further successful grant applications which built on the success
of CLASICC include:
— MRC: Adhesive complications after open and laparoscopic surgery. (CI: Prof.
— MRC/EME/NIHR: ROLARR trial: Robotic rectal cancer surgery (CI: Prof.
— MRC/EME/NIHR GLiSten trial: Fluorescence guide surgery (CI: Prof.
Details of the impact
CLASICC conclusively demonstrated: the technical and oncological safety
of laparoscopic colorectal cancer surgery; benefits for patients
(including improvements to quality of life outcomes) and healthcare
providers (including health economics needed to guide policy decisions and
effective criteria for patient selection for laparoscopic surgery).
Impact on guidance and service delivery
These outcomes had a direct bearing on the attitudes of surgeons and
healthcare providers. In 2000, at the time CLASICC was recruiting, NICE
guidance recommended "open rather than laparoscopic resection should be
the preferred surgical procedure" for patients with colorectal
cancer [A]. Six years later, CLASICC was one of only 7 RCTs, and the only
RCT to include rectal cancer, included in a NICE meta-analysis that
subsequently informed the updated NICE 2006 guidance [B]. The result was a
step change in recommendation to "laparoscopic surgery [should now be]
recommended as an alternative to open resection for individuals with
colorectal cancer". The implication was that, where appropriate,
laparoscopic surgery should be made available throughout the NHS for all
patients with colorectal cancer. Given that colorectal cancer is the third
most common cancer in the UK, affecting just under 40,000 people a year,
this has far reaching implications for the NHS. CLASICC documented the
potential benefits to health care providers through improved efficiency
and cost-savings [J], corroborating those outlined in the NICE 2006
meta-analysis: laparoscopic surgery results in a reduction in hospital
stay of 1.4 bed-days/patient, with the potential to increase to 4-10
bed-days/patient [B, F]. With ~ 30,000 patients undergoing colorectal
cancer surgery every year, at a bed-day saving of 1.4 days per patient,
this equates to ~17,000 bed-days saved per year, or around £7.5M saved per
annum. Society at large has also benefited with patients and families
returning to normal activity sooner, and a quicker return to work for
those in employment.
Impact on Policy
CLASICC played an instrumental role in changing healthcare policy
throughout the UK and internationally. Without the rigorous evaluation of
all aspects of laparoscopic colorectal cancer surgery (technical,
oncological, functional, health economics) it is unlikely that its
implementation would have quadrupled from 10% in 2009 to over 40% in 2012.
The change in NICE guidance in 2006 persuaded the Department of Health
(DH) to launch a £20 million initiative in 2008 to promote laparoscopic
colorectal cancer surgery throughout the NHS (LAPCO) [E]. A letter to NHS
Chief Executives from the National Cancer Director outlined the need for a
national training programme, and highlighted the potential cost-savings
and the obligation of PCTs to fund and to make laparoscopic colorectal
cancer surgery "normally available" [F]. LAPCO has successfully trained
over 300 colorectal surgeons in laparoscopic colorectal cancer surgery.
Impact on clinical practice and patient outcomes
CLASICC has allowed laparoscopic colorectal cancer surgery to be safely
disseminated throughout the NHS, in accordance with NICE guidance. More
patients now enjoy the benefits of the laparoscopic approach. Laparoscopic
resections undertaken in the NHS have increased from 10% in 2009 to 40% by
2012, which equates to ~9,000 additional patients per annum benefitting
from the laparoscopic approach; a trend that has been confirmed using
national NHS HES data [G]. This means that ~9,000 patients per annum are
recovering quicker from surgery, spending 1 - 2 days less in hospital, and
returning to normal activities several weeks earlier. Laparoscopic surgery
for colorectal cancer is fast becoming the standard of care throughout the
NHS, with the 40% UK adoption rate being one of the highest in the world.
The realisation that minimally invasive techniques, such as laparoscopic
surgery, reduces surgical trauma and facilitates patient recovery was
embraced as a central component of the National Enhanced Recovery
Programme, supported by the NHS Institute for Innovation and Improvement
and the NHS Cancer Action Team [H]. The combination of laparoscopic
surgery and improved perioperative management is considered the current
gold standard for major colorectal surgery, with the potential to further
reduce in-patient stays.
The successful implementation of laparoscopic surgery, supported by
CLASICC, has lead to the evaluation of other technologies to further
improve patient outcomes in colorectal cancer surgery. Robotic-assistance
may improve the capabilities of laparoscopic surgery and increase the
number of suitable patients. This is currently being tested in a follow-on
study to CLASICC undertaken by the University of Leeds: the MRC/EME/NIHR
ROLARR trial, a pan-World randomised controlled trial comparing
robotic-assisted with laparoscopic surgery for rectal cancer [I]. ROLARR
is at the forefront of surgical clinical trials research and is likely to
be as influential as CLASICC.
Impacts on International development
Internationally, the CLASICC has become a benchmark study for the design
of other colorectal cancer trials. These included an NCI multi-centre US
trial to gain further information about laparoscopic surgery in rectal
cancer [C] and the European COLOR II study. CLASICC has informed policy
decisions across the globe, for example being cited in the 2012 US
Position Statement on laparoscopic surgery for curable colon and rectal
cancer [D]. It has lead to laparoscopic surgery being accepted in many
different healthcare systems as the preferred treatment for colorectal
cancer. CLASICC is frequently cited as a point of reference in many
colorectal cancer publications and continues to be upheld as example of
rigorous evaluation of surgical technology that influenced surgical cancer
Sources to corroborate the impact
[A] NICE Technology Appraisal Guidance TA17. Guidance on the use of
laparoscopic surgery for colorectal cancer. December 2000. http://publications.nice.org.uk/laparoscopic-surgery-for-colorectal-cancer-ta17
National guidance against the use of laparoscopic surgery for
colorectal cancer, issued in 2000 prior to the publication of CLASICC.
[B] NICE Technology Appraisal Guidance TA105. Laparoscopic surgery for
colorectal cancer. August 2006. National guidance in support of the
use of laparoscopic colorectal cancer surgery, issued following CLASICC
- a step change from previous guidance issued in 2000. (Guidance
[C] Laparoscopic-assisted resection or open resection in treating
patients with stage IIA, stage IIIA, or stage IIIB rectal cancer. www.clinicaltrials.gov
NCT00726622. The US multi-centre trial, set-up in 2008, and
inspired by CLASICC to evaluate laparoscopic with open surgery for
[D] Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)
Evidence-Based Guidelines for the Laparoscopic Resection of Curable Colon
and Rectal Cancer.
2012 US guidance in support of laparoscopic surgery for colorectal
cancer, citing CLASICC outcomes.
[E] LAPCO: National training programme in laparoscopic colorectal surgery
national training programme in laparoscopic colorectal cancer instigated
by the National Cancer Director following the reporting of CLASICC and
evidence of the influence of CLASICC in changing national strategic
health policy. Over 300 UK colorectal surgeons trained in laparoscopic
[F] Letter from DH National Cancer Director to NHS Chief Executives - outlining
the need for a national training programme in laparoscopic colorectal
cancer surgery based on NICE evidence, the potential cost-savings, and
the obligation of PCTs to fund the programme to make laparoscopic
colorectal cancer surgery "normally available" (2008). DH gateway
[G] Morris,E.J; Jordan,C; Thomas,J.D; Cooper,M; Brown,J.M; Thorpe,H;
Cameron,D; Forman,D; Jayne,D; Quirke,P; CLASICC trialists Comparison of
treatment and outcome information between a clinical trial and the
National Cancer Data Repository. Br J Surg 2011; 98: 299-307. Evidence
of the trend to increased penetration of laparoscopic colorectal cancer
surgery performed within the NHS subsequent to CLASICC. PMID:
[H] Department of Health, Enhanced Recovery Programme
Department of Health policy, initiated in 2011, to integrate
laparoscopic surgery with enhanced recovery programmes for major
surgery. Highlights the beneficial role of laparoscopic surgery in a
package as standard of best care.
[I] Collinson FJ, Jayne DG, Pigazzi A et al. An international,
prospective, multicentre, randomised, controlled, unblended, parallel
group trial of robotic-assisted versus standard laparoscopic surgery for
the curative treatment of rectal cancer. Int J Colorectal Dis. 2012. 27(
2): 233-241. ROLARR trial protocol. ROLARR builds on the success of
CLASICC, has only been possible as a result of its success, and will
likely be as influential as CLASICC. PMID: 21912876
[J] Franks PJ. Bosanquet N. Thorpe H. Brown JM. Copeland J. Smith
AM. Quirke P. Guillou PJ. CLASICC trial participants. Short-term costs of
conventional vs laparoscopic assisted surgery in patients with colorectal
cancer (MRC CLASICC trial). British Journal of Cancer. 95(1):6-12, 2006. Manuscript
from CLASICC detailing health economic benefits arising from
laparoscopic surgery. PMID: 16755298