Ian G Finlay
Ian Finlay is a consultant colorectal surgeon at Glasgow Royal Infirmary. He was Lead Clinician and a founder member of the West of Scotland managed clinical network for colorectal cancer from 1999-2005. He is presently a “core member” of the Scottish Executive bowel cancer framework group. Ian Finlay was also a past honorary treasurer of the Royal College of Physicians and Surgeons of Glasgow.
SMJ 2006 51(1): 42-45
Introduction
Colorectal cancer is the third most common cancer in Scotland with approximately 3500 new cases per annum and the second most common cause of death from malignant disease. The incidence of the disease has risen over the past 50 years and is projected to continue to rise for at least another decade (1). Survival rates for patients with colorectal cancer are improving. Between the periods 1977-81 and 1997-2001 overall one year survival rates improved from 41% to 72% while the 5 year survival improved from 24% to 51% (2). Indeed in the last decade alone survival has improved by almost 10%. Despite these improvements survival rates in Scotland are less good than comparable Western European countries including Sweden, Holland and France. This may be partly due to the fact that Scotland is acknowledged to have one of the best cancer registries in the World with near complete data collection. In contrast, many countries base their survival on only a small proportion of cancer cases. It has however been shown that patients in Scotland present with more advanced disease than patients in countries with better survival rates suggesting that the discrepancy is not simply due to recording methods.
Improving outcomes for all cancers was made a priority by NHS Scotland in 2000 (3) with a particular focus on optimising treatment and improving waiting times. It is therefore an opportune time to review the recent developments that have taken place in the investigation and management of patients with colorectal cancer and to consider the likely impact of the initiatives currently being taken by the Scottish Bowel Cancer Framework Group (4). Readers will be aware that substantial textbooks have been devoted to both the clinical and scientific aspects of colorectal cancer; consequently in this brief article only a few of the clinically important advances can be reviewed. These include recent developments in surgical technique, preoperative staging, and the use of radiotherapy/ chemotherapy. There has also been a major initiative to improve the management of patients with colorectal cancer that could be broadly described as the “Colorectal Cancer Plan for Scotland”. The key components of this plan are described.
Surgery
Surgery is the most important single mode of treatment for patients with colorectal cancer because it is the only option that offers a realistic prospect of cure. It is self evident that to achieve this, the surgeon must remove the entire primary tumour with an appropriate margin of normal tissue that may include lymph node metastases. This is technically more easily achieved in the colon than the rectum explaining why historically local recurrence after resection was much more common in the pelvis than the abdomen.
Over 20 years ago it was shown that if the mesorectum was carefully removed with the rectum then local recurrence rates after apparently curative surgery for rectal cancer could be reduced from as high as 50% to <5% (5). This technique, known as TME (total mersorectal excision – see Figure 1), requires considerable skill and training and was the principal reason for the development of Coloproctology as a specialty. It is now known that TME is effective because it facilitates complete resection of the lateral border of the tumour near the pelvic side wall (circumferential resection margin) (6). Since “local recurrence” after rectal cancer surgery is invariably fatal, even in the absence of disseminated disease, this has been a major advance.
Further recent evidence of the importance of surgical technique and the use of TME has come from Sweden where the adoption of the technique after a national training programme led to a reduction in local recurrence rates (7). Happily, all major hospitals in Scotland now have at least one colorectal surgeon (many have several) who have been trained to use this technique. Indeed, in a recent study it has been suggested that the 10% improvement in survival observed during the past decade has been predominantly due to improved surgical technique (8), peri-operative care and by extrapolation, surgical subspecialisation (9,10).
The development of Coloproctology as a sub-specialty has brought benefits other than improved survival to the patient with rectal cancer. Most notable has been the reduction in the number of patients who require a permanent colostomy. Historically, abdominal-perineal resection of the rectum was necessary in more than 50% of patients with rectal cancer. In many specialist units fewer than 10% of patients with rectal cancer now require a permanent stoma due to developments in surgical technique and the availability of stapling instruments. This can result in problems with bowel function in a small proportion of patients. The loss of the “rectal reservoir” may produce frequency and urgency (anterior resection syndrome). Function is improved by fashioning a small colonic pouch immediately above the anastomosis (see Figure 2). It must however be only 5cm in length and within 8 cm of the anal margin. If the pouch is larger or anastomosed higher then the patient may develop difficulty in emptying the bowel of such severity that the pouch requires to be removed at a later date.
The majority of patients who succumb to colorectal cancer do so because of the presence of disseminated disease and in particular liver metastases. The increasing availability of safe partial hepatic resection (operative mortality <5%) over the past 10 years has been an important development for a small but important sub-group of patients. Initially the selection criteria for liver surgery were strict. Patients had to be fit, have few metastases and no evidence of extra-hepatic disease but for those who met the criteria the 5 year survival was up to 40% (11). My impression is that the liver units are adopting more “lenient criteria” as they incorporate various chemotherapy regimens and perform more extensive resections. Perhaps as few as 5% of all patients with colorectal cancer will be suitable and benefit from hepatic resection but for these patients it is literally the difference between “life and death”.
Pre-operative staging
Clinicians are aware that over the past 25 years there have been the most extra-ordinary advances in radiological techniques that have directly benefited patients. This is especially true of the colorectal cancer patient in whom preoperative staging now gives an accurate assessment of both the primary tumour and the extent of dissemination.
It is almost 25 years since the author and colleagues first made the observation at Glasgow Royal Infirmary that there were patients with colorectal cancer who had hepatic metastases that were detected by computed tomography (CT) but were not evident to the surgeon at laparotomy (12). We referred to these deposits as “occult hepatic metastases” and simply watched them grow on serial scanning because we had no treatment. That study remains one of the few to be published of the rate of growth of untreated hepatic metastases (13). It is all the more extraordinary that the CT scanner we used for these studies, although “state of the art” at the time, was a “crude machine” when compared to the fast spiral CT scanners that are routinely available in every hospital today. All patients with colorectal cancer should now be able to have a CT scan (or similar investigation) of the abdomen and chest prior to surgery. This has increased the detection of metastatic disease thereby improving therapy. Those patients with extensive metastatic disease often now avoid the discomfort and risk of radical surgery and are offered palliative chemotherapy as an alternative. Even if there is a risk of bowel obstruction major surgery can be avoided or delayed by the use of radiological stenting. Routine staging has also increased the number of patients found to have hepatic metastases that are suitable for resection. In carefully selected patients some surgeons might now consider a combined resection of the primary tumour and the hepatic metastases at the same operation.
The use of staging particularly benefits those patients with no evidence of metastasic disease because they can have a planned operation and a radical resection with a high probability of cure.
Positron emission tomography (PET) is a newer technique that has promise in detecting disseminated disease but the role has yet to be established, predominantly because there is a risk of false positive results in patients with inflammation or abscesses. Radiology has also greatly enhanced the staging of the primary rectal cancer. Since this is important in selecting therapy it has become a mandatory component of the patients work-up. Traditionally the size and fixity (extension of the tumour outwith the mesorectum to the pelvic wall) of rectal cancers was assessed on digital examination perhaps under anaesthesia. This has been superseded by the availability of pelvic CT, MRI and endorectal ultrasound. It is important to determine the extent of invasion of the primary tumour in two distinct situations. First, to identify tumours that are restricted to the bowel wall (T 1 & T2) since they may be suitable for local excision using the technique of trans-anal microsurgery. Early tumours in the rectum are more accurately staged by endo-rectal ultrasound rather than CT or MRI. It is even more important to identify those tumours that have breached the bowel wall and invaded the mesorectum and its surrounding fascia or adjacent structures (T3 &T4). There is a high risk that those tumours will be incompletely excised by surgery resulting in local recurrence. Advanced rectal tumours are best staged by CT or MRI(see Figure 3) (14). Patients with locally advanced primary rectal cancers should be considered for pre-operative radiotherapy in the first instance with surgery delayed until there has been tumour shrinkage.
It will be evident that the radiologist is an essential member of the team that treats colorectal cancer since important therapeutic decisions are now based on the radiologist’s opinion.
Radiotherapy
There is considerable variability in the use of radiotherapy in this disease. It can be given before or after surgery, in high or low dose and over a short or long period. It is a confusing subject but the criteria for offering patients radiotherapy are becoming clearer. First, radiotherapy is predominantly used in rectal cancer; not colonic cancer. Second, patients only gain a survival benefit if the radiotherapy is given pre-operatively. Radiotherapy given after surgery is therefore only palliative.
The aim of treatment is to reduce the risk of local recurrence after surgery by reducing tumour bulk and increasing the size of the resection margin. The benefits of pre-operative radiotherapy were unequivocally established in 1997 as a result of the Swedish rectal cancer trial (15). In that study, the local recurrence rate was reduced from 27% in the control group to 11% in the treated group. Of more importance the 5 year survival was improved from 58% to 48%. The study was severely criticised however because of the high local recurrence rate in the untreated group. Specialist centres at that time were reporting much lower local recurrence rates in untreated patients simply using the surgical technique of TME without radiotherapy. It was even suggested that they had been using radiotherapy to “treat bad surgery” rather than the disease. The problem of the non-standardised surgical technique was addressed by an important Dutch trial that reported in 2001(16). This study only included surgeons who had been trained in the use of TME; consequently all patients had appropriate surgery. Again preoperative radiotherapy lowered the local recurrence rate but by a much smaller margin from 8% to 2%. This study also demonstrated that there was little benefit for patients who had early disease (T1) or those who had disseminated disease. As one might have expected the maximal benefit occurred for those patients who had locally advanced primary tumours (T3 & T4) but it came at a price. Both trials have subsequently reported that patients who were given radiotherapy had significantly poorer function with regard to bowel frequency and incontinence. On the basis of their results, the Dutch group are now suggesting that a selective approach to the use of radiotherapy is probably best using pre-operative staging to determine those patients most likely to benefit. It is of note that this is the approach that has been used in Glasgow for the past decade (17).
Chemotherapy
It is out with the scope of this report to review the recent advances that have taken place in the provision of chemotherapy for patients with colorectal cancer given the numerous studies that are currently being undertaken. There are however some clear guidelines relating to treatment that can be briefly described.
Routine adjuvant treatment of colon cancer began in 1995 after a group from the Mayo Clinic reported that there was a 13% increase in survival for patients who were node positive and had been given adjuvant 5 FU and levamisole for one year. Subsequent studies showed that six months treatment was equally efficacious. In contrast, there is little evidence that adjuvant chemotherapy is beneficial in rectal cancer but it is often given especially in high risk cases. In rectal cancer chemotherapy is now more likely to be given pre-operatively in association with radiotherapy. Several studies are currently assessing the efficacy of this combined treatment.
In patients who require palliation, 5FU and leucovorin (5FU/LV) have been first line treatment for decades. Capecitabine is an orally administered fluoropyrimidine that offers an alternative to the injectable 5FU/LV. For those who fail first line treatment there is irinotecan and oxaliplatin. Current studies aim to determine the best “recipe” for using these drugs; sequentially or in combination. Although not a cure there has been a progressive prolongation in survival with these agents. The fact that this is now obvious to clinicians treating the disease is exemplified by the fact that an experienced colorectal surgeon recently said to the author that due to chemotherapy he could foresee the day when disseminated colorectal cancer becomes a “chronic disease”.
“Colorectal cancer plan for Scotland”
It is the aspiration of all National Health Services to provide high quality care, equitably to the entire population for all diseases. The “Scottish Cancer Plan” (2) in conjunction with the Bowel Cancer Framework for Scotland (3) is the first national initiative that aims to achieve this for colorectal cancer. It particularly recognises that in the absence of a “magic bullet” cure, advances in survival depend upon optimising best practice in the treatment of patients with the disease and seeking to detect pre-malignant disease in the asymptomatic population (screening).
Although the plan included all aspects of the management of colorectal cancer there were two particularly important components. First, the Clinical Standards Board for Scotland (CSBS) was created as a Special Health Board with the specific remit of defining the standards for the management of colorectal cancer that should be achieved by all service units across Scotland. It was important that these standards were not imposed but arose from interdisciplinary agreement. The standards include important clinical measurements such as the percentage of patients who undergo pre-operative staging, have prophylactic antibiotics or have complete resection of the primary tumour on histological examination. Other standards relate to process and organisation that have been described as the “patient journey”. The CSBS then undertook an analysis of the service in 2001 based on site visits and found that in many cases the Service was either deficient or the information required was unavailable (18).
Thereafter Regional Managed Clinical Networks (MCN) were created in the West, East and North of Scotland. Although the evolution and mode of working evolved differently between regions the remit of delivering the CSBS standards remained the same(19). The disease specific networks function as sub-groups of the regional MCN and comprise all individuals who are involved in the management and treatment of the patient. As an initial step the colorectal networks developed an audit base and have published their results. By May 2005 all three regional Networks had achieved the CSBS Standards for the important components of clinical care although there remained variability between service units within networks. Indeed such has been the progress in the past 5 years that it has been suggested that the standards should now be made more stringent. Audit Scotland in a recent review of colorectal cancer services made the comment that “Scotland’s managed clinical networks have made good progress in auditing clinical practice and promoting high quality care” (20).
Although the Network and Audit Scotland reports are pleasing with regard to the progress that is being made in clinical care they also highlight severe deficiencies in the service with regard to the waiting times for outpatient consultation and diagnostic tests. There are several reasons why this has occurred. First, there have been several cancer awareness programmes in the UK (including the recent successful West of Scotland campaign) that have increased demand, especially of the “worried well”. Second, there has been a rapid increase in the number of patients having colonoscopy as the primary investigation for large bowel symptoms. Colonoscopy is a difficult technique with a long learning curve for trainees. Third, pre-operative staging has placed high demands on radiological services. In order to achieve the national target of treatment for all patients with colorectal cancer within 62 days these challenges will require to be met. The Scottish Executive Bowel Cancer Framework Group and the Regional Networks are currently introducing a number of initiatives that should improve the situation. These include the development of electronic referral systems for general practitioners that can in due course be “electronically triaged”. Protocols have also been developed for the referral and investigation of patients based upon risk stratification of presenting symptoms. These should allow the Service to make the best use of existing resources while capacity is developed. In this respect nurse specialists are likely to comprise an increasing proportion of the colonoscopy work force with the development of dedicated training programs. Reduction in waiting times should also be gained by improving the organisation and management of the service such as co-ordinating and prebooking tests, redesigning patient pathways to eliminate unnecessary steps and controversially by abolishing individual clinician waiting lists.
A further exciting initiative has been the Executive decision to introduce population bowel screening for all of Scotland in 2007. This promises to be of great benefit and follows on from the results of the pilot study of faecal occult blood testing that began in Tayside, Grampian and Fife in 2000. It has been estimated that as many as 150 colorectal cancer deaths per annum could be prevented by introducing screening. This compares with the current breast and cervical programs that prevent only 40 and 26 deaths respectively. Although screening has been shown to increase the proportion of early cancers that are detected the “bigger prize” will be the detection and eradication of asymptomatic polyps. Data from the USA suggests that population programs designed to eradicate polyps will reduce the number of cancers that subsequently develop.
Conclusion
Although the survival rates for colorectal cancer have been poorer in Scotland than in comparable western countries there is evidence of substantial improvement over the last decade. This has been attributed predominantly to improvements in surgical management and sub specialisation. We have yet to see the survival benefits that may accrue from advances in chemo/radiotherapy. The Scottish Executive in the Cancer Plan has made the improvement in cancer survival a high priority. The “colorectal cancer action plan” addresses every aspect of the management of the disease from the referral from primary care to the completion of treatment. Uniquely, this is all measured against standards that were drawn up by the profession. In no other country in the world has there been such a comprehensive effort to ensure that patients are treated according to “best practice”. In addition, population bowel screening will be available throughout Scotland from 2007.
Having optimised the Service we would hope that survival rates in Scotland from 2008 onwards will not only match but exceed those of our European neighbours.
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