Case Study 5. Pathology research led to an international reduction in rectal cancer recurrence and death by improving multidisciplinary clinical practice
Submitting InstitutionUniversity of Leeds
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Oncology and Carcinogenesis
Summary of the impact
Postoperative local recurrence affects 20-30% of patients with rectal
cancer. Between 1993 and 2013, University of Leeds researchers identified
the importance of pathology studies to show a disease-free margin around
the excised tumour and how to predict this margin routinely and accurately
using simple histopathology and preoperative MRI.
We also used photography in the pathological assessment of the quality of
surgery and were instrumental in the adoption of modern techniques by
professional organisations around the world.
Following adoption of our techniques in England and Scotland, local
recurrence has halved with 10% better survival and cost savings of £60
million. Our methods have also become the gold standard in the treatment
of rectal cancer patients around the world.
Rectal cancer is common with 14,999 cases annually in the UK and 446,400
globally. Around 20-30% of patients develop pelvic local recurrence, which
can lead to a very painful and unpleasant death six to nine months later.
More than 90% of individuals with pelvic local recurrence die within three
years of initial surgery.
In 1994 Phillip Quirke (Professor of Pathology 1982 to present),
Michael Dixon (Professor of Gastrointestinal Pathology 1970 to
2001), David Johnston (Professor of Surgery, 1977-1998) and others
at the University of Leeds published research showing that local
recurrence of rectal cancers was due to inadequate resection at the
circumferential surgical margin.1 In this prospective study of
190 patients with rectal cancer we developed a simple routine dissection
method for identifying tumour at the circumferential margin and showed
that it was present in 25% of specimens where the surgeon thought the
resection was potentially curative and 36% of all cases. This work also
showed that inadequate resection at the circumferential surgical margin
predicted local recurrence and survival fell from 66% to 15% and that NHS
histopathologists could use this method to predict prognosis.
Subsequent work (also by Professors Quirke, Johnston and Dixon)
published in 2002 showed that frequency of circumferential surgical margin
involvement varied between surgeons and was dependent on how well total
mesorectal excision was performed.2 Our work showed surgical
skill was associated with rates of local recurrence and individual patient
survival both of which could be improved with better dissection technique.
Professor Quirke developed a simple photographic method for
grading the quality of total mesorectal excision. The MRC CR07 trial in
2009 showed quality of surgery assessed this way predicted outcomes at
three years3, and this was confirmed in the Dutch Total
Mesorectal excision +/- radiotherapy trial surgical specimens reviewed by
In collaboration with Professor Bill Heald and Mr Brendan Moran (Pelican
Centre, Basingstoke) and Dr Gina Brown (Royal Marsden Hospital, London) we
conducted the Mercury study showing circumferential surgical margin status
can be accurately assessed and outcome predicted preoperatively by MRI.4
One issue that became apparent during these studies in the early 2000s
was that outcomes in patients with low rectal cancer did not improve with
improved total mesorectal excision technique. Work by Professors Quirke,
Johnston and Dixon, showed this was due to on going high rates of
circumferential surgical margin involvement (20-30%) and high perforation
rates (20%) during abdominoperineal excision.5 This was
confirmed in the Mercury trial in tumours < 6cm from anal verge.
In 2008, Professor Quirke with Paul Finan (Professor of
Surgery, Leeds Teaching Hospitals NHS Trust [2010-present]) and Nicholas
West (PhD student/Lecturer 2009-present) then showed through work in Leeds
and a collaborative multinational study that a newer more radical approach
(extralevator abdominoperineal excision) developed by Swedish surgeon
Torbjorn Holm (Karolinska Hospital, Stockholm) reduced circumferential
surgical margin positivity and perforations by excising more tissue around
the tumour.6 The Mercury2 study has shown a relative reduction
in CRM involvement by 55% based on this approach.
References to the research
 Adam IJ, Mohamdee MO, Martin IG, Scott N, Finan PJ, Johnston D,
Dixon MF, Quirke P. Role of circumferential margin involvement in
the local recurrence of rectal cancer. Lancet. 1994; 10; 344(8924):
 Birbeck KF, Macklin CP, Tiffin NJ, Parsons W, Dixon MF,
Mapstone NP, Abbott CR, Scott N, Finan PJ, Johnston D, Quirke P.
Rates of circumferential resection margin involvement vary between
surgeons and predict outcomes in rectal cancer surgery. Ann Surg. 2002;
 Quirke P, Steele R, Monson J, Grieve R, Khanna S,
Couture J, O'Callaghan C, Myint AS, Bessell E, Thompson LC, Parmar M,
Stephens RJ, Sebag-Montefiore D; NCRI Colorectal Cancer
Study Group. Effect of the plane of surgery achieved on local recurrence
in patients with operable rectal cancer: a prospective study using data
from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet.
2009; 373(9666): 821-28.
 MERCURY Study Group. Diagnostic accuracy of preoperative magnetic
resonance imaging in predicting curative resection of rectal cancer:
prospective observational study. BMJ. 2006; 333: 779-78. Quirke P
 Marr R, Birbeck K, Garvican J, Macklin CP, Tiffin NJ, Parsons WJ, Dixon
MF, Mapstone NP, Sebag-Montefiore D, Scott N, Johnston D,
Sagar P, Finan P, Quirke P. The modern abdominoperineal excision:
the next challenge after total mesorectal excision. Ann Surg. 2005;
 West NP, Finan PJ, Anderin C, Lindholm J, Holm T, Quirke
P. Evidence of the oncologic superiority of cylindrical
abdominoperineal excision for low rectal cancer. J Clin Oncol. 2008;
Details of the impact
Researchers at the University of Leeds clearly identified that widely
used surgical techniques were associated with local recurrence and death
in patients with rectal cancer. We developed simple routine methods for
assessing tumour involvement in the circumferential surgical margin and
showed how these could be used to predict local recurrence and survival
and improve surgical performance. Our concepts of the importance of the
circumferential surgical margin, Leeds dissection methods, photography of
the quality of surgery, introduction of routine preoperative MRI, and best
practice total mesorectal excision and extra levator excision methods have
become the gold standard in the treatment of rectal cancer patients around
Health and welfare
In the 1990s, patients diagnosed with rectal cancer faced a 20-30% risk
of local recurrence, which in turn is associated with high rates of
mortality and can be a very painful and unpleasant way to die.a,b
We were the first to conclusively show that not properly excising the
tumour in the circumferential surgical margin strongly influenced local
recurrence and death, involvement was found in 25% of cases where the
surgeon believed the operation had been curative. We also highlighted the
importance of histological assessment in predicting recurrence and
Our work has improved the surgical skills and techniques used in total
mesorectal excision, abdominoperineal excision and the histology and
imaging required to support and guide treatment. Through our studies
showing MRI could be used before surgery to assess the circumferential
surgical margin and predict outcome, this has become the standard approach
in Europec and around the world. Patients can now be reassured
that they are receiving the best possible surgical techniques which can be
easily monitored and their chance of cure and survival have improved
dramatically from that seen two decades ago.
In 2013 our techniques have led to an impressive 40-50% reduction in
rates of local recurrence in curative surgery across England, Scotland,
Sweden, Denmark, British Columbia, Slovenia, Belgium Norwayd
and Spaine and survival in curative cases improved by 8% d.
This means >1800 fewer patients suffering the consequences of local
recurrence and >1,000 more surviving each year in the UK.
Society, culture and productivity
Between 2003-2006 we received £6 million in Department of Health funding
to roll out the use of the histological, MRI and surgical techniques we
had developed to 1,639 individuals from 183/186 English bowel cancer
teams.f Professor Quirke led the pathology training, Dr Gina
Brown MRI and Professor Heald at the Pelican Centre, Basingstoke led on
the surgery education programme. Between 2011 and 2013 funded by the NHS
(£1 million) to provide LOw RECtal cancer courses throughout England
training 1,045 staff of147/151 English Trusts.
We conservatively calculate that each local recurrence costs the NHS more
than £40,000 in direct medical expenses alone f saving
£60,000,000 per anuum
NICE has recommended use of our concepts g and the practice
of all members of the multidisciplinary team in the NHS from surgeons,
pathologists, radiologists and oncologists has radically changed.
By defining the planes of surgery seen after operations for rectal cancer
and showing in a major clinical trial that rapid simple photographic audit
(using low cost digital cameras or good quality mobile phones) of the
quality of rectal cancer surgery was possible, we have revolutionised how
these procedures are performed and assessed. This is now being
investigated as a tool in other cancers such as pancreas, oesophageal and
Our methods have now been introduced into many professional guidelines
around the world - both surgicalh and pathologicali
and Trial protocols in Englandj and Europe
In addition, we have actively disseminated these techniques and standards
on six continents in conjunction with the Pelican Cancer Charity.
Protocols, trial protocols and educational material have been made freely
available on the web and by DVD. Countries we have run education
programmes include many in Europe as well as Argentina, Chile, Russia,
Toronto, USA with demand continuing to rise.
Sources to corroborate the impact
[a] Medical Research Council Rectal Cancer Working Party. Randomised
trial of surgery alone versus surgery followed by radiotherapy for
mobile cancer of the rectum. Lancet. 1996 Dec
Describes the low survival and high local recurrence rate in this trial
before knowledge of the importance of CRM, MRI and improved surgery.
[b] Kodeda K, Derwinger K, Gustavsson B, Nordgren
S.Colorectal Dis. 2012 May;14(5):e230-7.
doi: 10.1111/j.1463-1318.2011.02895.x.Local recurrence of rectal
cancer: a population-based cohort study of diagnosis, treatment and
Describes the severity of local recurrence and the difficulty managing
it even today if it is not avoided
[c] Valentini V et al; Scientific Committee. Multidisciplinary Rectal
Cancer Management: 2nd European Rectal Cancer Consensus
Conference (EURECA - CC2). Radiother Oncol. 2009 Aug; 92 (2): 148-63.
European consensus conference mandating our pathology, MRI and TME
surgery to be updated in 2013
[d] Bernstein TE, Endreseth BH, Romundstad P, Wibe
A; Norwegian Colorectal Cancer Registry. Improved local
control of rectal cancer reduces distant metastases.
Colorectal Dis. 2012 Oct;14(10):e668-78. doi:
Description of local recurrence and survival in Norway over this period
PQ trained Norwegian pathologists in his techniques
[e] Impact Of A Multidisciplinary Team Training Programme On Rectal
Cancer Outcomes In Spain. Ortiz H, Wibe A, Ciga MA, Lujan J,
Codina A, Biondo S; The Spanish Rectal Cancer Project. Colorectal Dis.
2013 Jan 25. doi: 10.1111/codi.12141.
Description of a repeat of the Norwegian project in Spain reproducing
the improvements in Norway using our Pathogy techniques, MRI and TME
[f] Miller AR, Cantor SB, Peoples GE, Pearlstone
DB, Skibber JM.
Dis Colon Rectum. 2000 Dec;43(12):1695-1701; discussion 1701-3. Quality
of life and cost effectiveness analysis of therapy for locally recurrent
[g] The National Institute for Health and Clinical Excellence (NICE).
Colorectal cancer: the diagnosis and management of colorectal cancer.
Recommends the use of our pathology techniques, preoperative MRI and
[h] Practice parameters for the management of rectal cancer
Monson JR, Weiser MR, Buie WD, Chang GJ, Rafferty JF, Buie
WD, Rafferty J; Standards Practice Task Force of the American Society of
Colon and Rectal Surgeons.
Dis Colon Rectum. 2013 May;56(5):535-50. doi:
Recommends the use of our methods for standard care in USA
[i] Royal College of Pathologists. Guidelines for dissection and
reporting of colorectal cancer 2007.
(update due 2013) and College of American Pathologists Protocol for
the Examination of Specimens From Patients With Primary Carcinoma of the
Colon and Rectum
Trial protocols of past and current phase III rectal cancer trials MRC
Clasicc, MRC CR07, EME Rolar, NCRI Aristotle, NCRI Enrol, Trec, LOREC