Deaths from bowel cancer have halved for women and fallen by a third among men over the past 40 years, although the disease is still the third leading cause of death from cancer, according to new figures from the Office of National Statistics. “We can cure between two-thirds and three-quarters of people with bowel cancer depending on the location – in some regions people tend to go to the doctor only when it is too late,” said Professor Bill Heald OBE, director of surgery at the Pelican Cancer Foundation. “With good screening and greater willingness to discuss bowel cancer, there are much better opportunities now to achieve positive outcomes. It is unquestionably the most important of the cancers, where the most impact can be achieved.” Through early surgical intervention, the disease can often be cured. However, while surgery cures more patients than any other intervention for cancer, only 1.3% of cancer research money is spent on the advancement of superior surgical techniques. In fact, there is an increasing body of evidence to suggest that colorectal cancer is the most technique dependent of all malignancies. There is a greater difference in outcome in terms of cure, the number of permanent colostomies necessary and in various other disabilities, including impaired sexual function, than any other cancer. Striving to address this issue is the Pelican Cancer Foundation, which focuses on advancing the most effective techniques in precision surgery for bowel, liver and urological cancer. (The charity’s name is derived from the words “pelvic” and “liver cancer”.) The organisation has grown from the pioneering work in bowel cancer surgery of Prof. Heald; Brendan Moran, Pelican’s colorectal director; and other colleagues, who identified a need to address the variation seen in surgery outcomes across the UK – both in terms of survival and in the quality of life experienced by patients.
TME surgery
Prof. Heald developed the Total Mesorectal Excision (TME) technique for rectal cancer, which has now become the “gold standard” for rectal cancer surgery. Importantly, refinement of bowel cancer surgery, particularly TME has been proven to save more lives than conventional methods. “TME is concerned with the precise removal of the optimal block of tissue to safely encompass the cancer – including its local spread,” Prof. Heald explained. “When Pelican was first established, it was apparent that there was a need to ensure the best possible planning of an operation, precise performance of the operation, along with a programme of teaching on how to achieve excision of exactly the right area of tissue.” Prof. Phil Quirke, a pathologist from Leeds, observed that there were significant variations in outcomes from rectal cancer surgery. “The reason for these huge differences lay with the precision of the surgeon,” explained Prof. Heald. “Prof. Quirke introduced the idea of auditing the TME specimen to look at the margins to see if there are any microscopic ‘tentacles’ of cancer. This can indicate whether malignant cells have been left behind, which would explain why regrowth of the cancer may have occurred.” Unfortunately, if cancer is detected at the circumferential resection margin (CRM) of the removed specimen then local recurrence and poor survival are highly probable. Studies have shown that rates of cancer found at the CRM are greater than 20% and vary from surgeon to surgeon. While the importance of auditing the excised specimen became evident, Pelican was simultaneously working with pioneering radiologists – including Dr Gina Brown at the Royal Marsden Hospital, who saw the value in the application of MRI in planning the management of rectal cancer surgery. “The use of MRI has been major step forward,” commented Prof. Heald. “Advances in imaging techniques have made it possible to identify, preoperatively, those rectal cancers which could threaten the surgical margins, which enables the team to make appropriate pre-operative treatment decisions on an individual patient basis.” As development of the TME approach gained momentum, Prof. Heald and Brendon Moran were asked to organise a series of TME workshops in Stockholm, Sweden, and the results subsequently caused shockwaves across the international community of colorectal surgery.
During a study into rectal cancer treatment, carried out in the Stockholm area, the surgical failure rate of rectal cancer more than halved due to the TME technique being introduced. This was the first time that practical surgical workshops with video relay had been proven to impact on recurrence, survival and quality of life in a whole community. The rate of permanent colostomies for this operation also dropped; less than one patient in five needed a permanent colostomy after TME which is about a third of the national average. “The approach of planning with MRI, teaching precise techniques of surgical removal of the cancer, along with auditing of the specimen, produced significant results showing long-term improvements and cure – and brought about a revolutionary change in attitude in the approach to other major cancers,” Prof. Heald continued. “Dr Jane Maher, a medical oncologist and chief medical officer at the cancer charity Macmillan, commented that the best buy for the new century for improving cancer outcomes would be to improve the quality of surgery. She learned of the results in Sweden and persuaded Macmillan to support a pilot study to see if these could be repeated in the UK. We subsequently visited Nottingham and conducted some live surgery cases, relaying images to surgeons, in the Trent region. The pilot study was a great success.” Cancer Tsar, Prof. Mike Richards also learned that the approach resulted in vastly improved outcomes and secured Government funding for Pelican’s MDT (multidisciplinary team) TME development programme – the aim being to implement better surgery and auditing to improve outcomes, as well as to improve quality of life. “An important part of the teaching programme has been to promote understanding that the block of tissue that has to be removed from the pelvis, to treat rectal cancer, is surrounded by nerves on which sexual function depends. In the past, impotency used to be extremely common in men and female sexual function was also often interfered with in subtle ways – which few people have reported on,” he added, commenting: “We have spread the message that sexual function can be preserved and optimal cancer results achieved – by only taking out the tissue that needs to be removed and leaving behind that which must be preserved.” The National MDT TME Development Programme has been introducing the strategy to all National Health hospital MDTs (comprising surgeons, radiologists, oncologists, pathologists and specialist nurses) treating colorectal cancer, facilitated through a two-day course for the whole team. This is being supported by intensive workshop-based training for the radiologists performing the MRI. The surgical team at Pelican, with Prof. Heald, has now conducted hundreds of TV-based operation demonstrations and practical workshops and, as a result of the National Training Programme, the results achieved at Basingstoke are now repeated throughout the country. The TME technique has also been formally adopted in Norway, Sweden, Denmark, Holland, Germany, Austria and Switzerland. “We are starting to see the fruits of this work in terms of improved outcomes for cancer patients – I believe this has had a more significant impact than expensive drugs. Jane Maher was right when she said that the best buy is to improve quality of surgery,” commented Prof. Heald.
Further research in TME and MRI
The important role of MRI in the TME approach was recently highlighted by an audit of a single cancer network. This showed that the rate of cancer being present at the surgical margins was reduced from 27% to less than 5% in patients who underwent treatment following multidisciplinary team (MDT) discussion of pre-operative MRI scans. Patients with clear margins on MRI underwent surgery alone and patients with threatened margins received preoperative treatment e.g. chemo/ radiotherapy to downsize the cancer prior to surgery. “Dr Gina Brown has been responsible for training a radiologist from almost every bowel cancer unit – spending a whole day teaching them how to produce pictures at optimum angles to visualise the cancer in relation to the mesorectum and the tissue that is going to be excised, in order to predict which patients will benefit most from pre-operative radio and chemo therapy,” Prof. Heal explained. “Her work has had a major impact – no more than 20% of the hospitals in Europe are getting the quality of imaging that we are now getting across the UK. It makes a significant difference to patients as radio therapy and chemotherapy can be associated with considerable complications and, where possible, it is preferable to avoid administering these treatments.” With funding from the Wessex Cancer Trust and Siemens Medical UK, Pelican has taken its investigations into MRI further and has completed the first phase of a prospective, European, multidisciplinary project, called MERCURY. The aim of the study was to demonstrate the accuracy and feasibility of MRI (Magnetic Resonance Imaging) as a method of assessing rectal cancer.
The MERCURY study was successful in achieving its aim – to show that preoperative MRI was equivalent to the corresponding post-operative pathology result and can therefore be used by the multidisciplinary team for pre-operative treatment planning. It also provided a comprehensive database for the analysis of many other aspects of the management and treatment of patients with rectal cancer. In addition, Pelican now has the data from the five-year follow up, which offers an insight into the long-term quality of life for patients and the use of MRI for very low rectal cancer. “MERCURY showed that patients with low rectal cancers – i.e. within 6 cm of the anal verge, have a higher risk of incomplete surgical excisions,” explained Sarah Crane, chief executive at Pelican. “These patients have worse outcomes in terms of survival and quality of life than other patients with rectal cancer, so Pelican will be focusing closely on addressing this.” The study group has now planned a “MERCURY low rectal cancer study”, using MRI-based, multidisciplinary team management. The primary aim of this study is to reduce the rate of incomplete tumour excisions in these patients from 30% to less than 10%. This will reduce the rates of local tumour recurrence and improve overall survival for patients. (Pelican is now recruiting for the multinational, multi-centre trials on low rectal cancer). Also in progress is a multicentre, randomised clinical trial, EXPERT C, investigating the combined use of drugs, TME and MRI. Led by Prof. David Cunningham, from the gastrointestinal trials unit of the Royal Marsden Hospitals, the trial is comparing oxaliplatin (Eloxatin), capecitabine (Xeloda) and pre-operative radiotherapy with or without cetuximab, followed by TME, for the treatment of patients with high risk rectal cancer.
TME and future technologies
Examining the role of future technologies, Pelican is now evaluating the potential of robotics in the use of TME. Prof. Heald recently visited South Korea to view the technique in action, but believes that many questions still need to be addressed: “There is controversy over whether it is possible to perform a good TME procedure laparoscopically and I have been investigating whether robotic surgery has potential in this field. However, if I was a patient, I would want to know: ‘how many cases have been performed?’ and ‘what results have been achieved?’ “Furthermore, what are the complication rates and how many people experience poor bowel function or impotence? These issues need careful audit – after all, these are the issues that really matter to patients,” commented Prof. Heald. “In South Korea, robotic surgery is being aggressively marketed and patients assume they are getting treatment that is much better, but that remains to be proved. We need an objective judgement on what is being achieved by this approach and to fully understand the criteria for open vs laparoscopic surgery,” he asserted.
Prostate treatment
Although colorectal cancer is the foundation’s main focus area, research is also being undertaken into cancer of the liver, bladder, kidney and prostate. In 2005, a dedicated urological treatment unit in Basingstoke was initiated. The unit specialises in delivering current modes of surgical treatment for prostate cancer but, more importantly, pursues advances in technology and techniques to improve treatment for patients. Consultant urological surgeon, Richard Hindley, has pioneered the use of the high powered KTP (green-light laser) for benign prostate enlargement with considerable success. This vaporises prostate tissue and is set to replace traditional prostate surgery with its inherent side effects of incontinence and impotence. Pelican is also interested in furthering advances in minimally invasive technology such as High Intensity Focused Ultrasound (HIFU). This technique employs sound to destroy small prostate cancer tumours, obviating the need for surgical removal and, as with the greenlight laser, the technology reduces the possible side effects from surgery. The clinical trials, carried out at UCL/UCH, are being led by Hashim Uddin Ahmed, MRC clinical research fellow and specialist registrar in urology, and Mark Emberton, clinical director for cancer services at UCLH. The research is leading the world in the concept of focal therapy and the results, to date, are very promising. These advances will be discussed at a colloquium being held by Pelican, along with some of the leading oncologists in the US, which takes place in New York on 13 May 2010. “Prostate cancer is a difficult disease, particularly as the PSA test has poor specificity with many false positives. A very large number of people get investigated on the basis of PSA results and a large number are operated on. However, a cancer is only a serious issue if it causes harm and there are many prostate cancers that, if left alone, would not spread,” commented Prof. Heald. “Nevertheless, prostate cancer is an important cause of death and it would be a major step forward if we could identify exactly which cancers were going to grow, become invasive and spread to other places. Over treatment is something which must be avoided as there is a risk of incontinence and impotence. Therefore, we are focusing on the principle of precision – focal therapy, coupled with very accurate imaging, offers the potential to treat the prostate without having to perform radical prostatectomy and with the minimum of side effects.”
Prostate and MRI
Pelican believes that men suspected of having early prostate cancer (for example, after a PSA test) have an important new choice – highly specialised MRI scans can provide as much as 95% certainty that there is no pressing need for surgery or even for biopsy. Pelican backed research at University College London, suggests that MRI, including T2 and dynamic contrast enhanced sequences, before biopsy, may provide early risk-free reassurance that no potentially dangerous cancer is present. Should the MRI images show suspicious areas, a closer targeted biopsy can then be used to either confirm or clear that region with greater precision – a significant improvement on the current “blind” practice. The advantage of MRI before biopsy is that it:
• Can reach 25% more of the prostate gland than a standard biopsy.
• Where significant tumours exist the MRI provides a map for accurate biopsy.
• It will not identify “IDLEs” – i.e. harmless lesions.
This will reduce the number of men requiring biopsy and suffering the negative distress of a cancer diagnosis.
Curing cancer for present generations
“Alongside our research portfolio, providing state-of-the-art facilities to enable surgeons to hone their skills is a key part of our strategy to improving cancer outcomes – training should be a continuous process,” commented Sarah Crane. “We are also keen to engage with further MDT development – multidisciplinary team working is a core aspect of improving cancer care and there is much more that can be done to progress this. “MDT training has the ability to ensure a more consistent approach to patient care. There are also benefits to patients participating in trials, so this needs to be encouraged – while teams also feel valued if they are taken out of their hospitals and have the opportunity to discuss their current clinical and process delivery of care. You cannot underestimate the value of this type of team building,” she continued. “In the future, our research portfolio will continue to slowly and carefully grow – offering patient benefit through precision surgery.” Reflecting on the principles behind Pelican’s work, Prof. Heald concluded: “Ultimately, a great deal is invested into the science of cancer that may or may not benefit future generations, but we want to ensure those currently living with cancer also benefit. “With earlier diagnosis, I hope that we progress towards curing most people with bowel cancer. With a multi-faceted attack, and by targeting earlier stage tumours, we should be able to achieve this. Half of all cancer malignancies start in the pelvis – it is an important area – and through investment in research and training in effective surgical techniques, we can make a major difference to outcomes in the present.”