Over the past 20 years the number cases of colorectal cancer has increased significantly in Ireland; however once adjusted for changes in the age distribution of the population over time the rate has remained stable. Internationally colorectal cancer rates have stabilised in economically developed countries and Ireland is no exception in this regard [
18]. In comparison to other European countries, in 2008 Ireland had a higher incidence rate than the EU average and 23% higher than the rate in the United Kingdom [
19]. In the European region incidence has increased in males at a greater rate than female incidence during the period 1988 to 2008 [
20]. Survival was just below the EU average but similar to the United Kingdom [
21]. The improvements in survival reported in this paper were also seen in other European countries during the 1990s and early 2000s [
21]. European 5 year survival of colon cancer increased from 54.2% in the period 1999-2001 to 58.1% in 2005-2007, and from 52.1% to 57.6% for rectal cancer over the same period [
22]. Although Irish survival improved, it is still lower than the European average [
22]. Our data indicates that survival continued to improve for cases diagnosed during 2005-2009. While we did not have detailed information on the dose and intensity of chemotherapy and radiotherapy regimens, better uptake in and application of treatment options during 1995-2009 correlate with the improvement in survival.
Stage
One of the striking findings of this study was that almost half of cases had relatively late stage at diagnosis (stage III/IV) and, over the period under investigation, the proportion with stage III/IV disease increased from 42% to 50%. The increase in stage III/IV cancers is likely to be as a result of more comprehensive investigation in the peri-operative period, with improvements in imaging and diagnostic methods, resulting in a significant shift in stage allocation from stage I/II to stage III/IV over the years 1995-2009. Another possibility is that the number of nodes taken at resection increased over the period 1995-2009, thereby leading to a situation where the probability of finding a positive node(s) increased commensurately, which would have tipped the balance in favour of stage III/IV over stage I/II according to UICC-TNM, 5th edition. However, we do not have details on node count to support this hypothesis. This question will be addressed in a more comprehensive study of stage migration in colorectal cancer at this registry.
If effective, screening has the potential to change the stage distribution of colorectal cancer in the population. As regards FIT-based screening, which is being implemented in Ireland, Cole et al reported that colorectal cancers were detected at significantly earlier stages in those invited to participate in a screening programme using FIT [
23]. In a health technology assessment for Ireland, it was estimated that, by year 10 of a programme, the percentage of cases diagnosed at stages I/II would increase from 46% to 53% and stages III/IV decrease from 54% to 47% [
10]. These estimates were based on screening targeted at those aged 55-74 with a best case scenario uptake of 53% (based on the UK experience of FOBT screening) [
24]. Similar uptake has been achieved in pilot FIT screening in Ireland [
25]. The BowelScreen programme, which has recently commenced, is initially inviting individuals aged 60-69. While the stated intention is to eventually include 55-74 year olds, this is likely to take a number of years due to the development of colonoscopy capacity. Therefore the estimates of potential reductions in late stage disease are very unlikely to be achieved by year 10 of the programme.
Mortality
In 2008 Ireland ranked midway of 30 European countries in relation to mortality, similar to the EU average but marginally higher than the United Kingdom [
19]. Annual decreases in age standardised mortality rates for colorectal cancer in males and females were observed in this study. However this concealed significant increases in the mortality rate for rectal cancers of 2.4% in males and 2.8% in females. Scrutiny of European data reveals that most countries have experienced static mortality rates over the past 15-20 years. However a few, in addition to Ireland, have described increases. These include Spain, with an APC of 3.5% during 1994-2005, Malta with an APC of 5.2% during 1994-2008 and among selected registries in Germany with an APC of 17.1% during 1998-2007 [
26]. In terms of potential explanations for these trends, the first that must be considered is whether it might be an artefact of coding of rectal cancer deaths. We have shown that there was a significant decline in the annual death rate for pooled colorectal sites. Yet, there was a steeper decline in the rate of colon deaths, with a compensatory increase in the rate for ‘rectum’ deaths. This suggests that there may have been a subtle shift in death certificate coding allocation from ‘colon’ to ‘rectum’ over the period we have examined. It has long been recognised that physicians tend to report non-specific cancer sites on death certificates; thus, if physicians change how they record cause of death on the death certificate over time, this may induce an apparent change in mortality rates [
27]. In 1981, Percy et al reported that misclassification led to over reporting of colon cancer deaths and underreporting of rectal cancer deaths [
27]. More recently, in the US, Yin et al reported inaccurate coding of underlying cause of death, with the vast majority of misclassifications being colon cancers incorrectly classified as rectal cancers [
28]. Further investigation is warranted to explore the extent and nature of misclassification on death certificates in European countries in recent years, perhaps comparing countries with rising and static rectal cancer mortality rates.
Another possible explanation of the observed increase in rectal cancer mortality is patterns in treatment utilisation. Pre-operative radiotherapy has been recommended for resectable rectal cancer in recent years [
29,
30] and in line with this the proportion who received pre-operative radiotherapy has increased markedly since 2000, in Ireland and in other countries [
31]. However Carsin et al have reported low use of radiotherapy in Ireland (27%) [
31] compared to US and EU populations (46%-62%) [
32‐
34]. Moreover, although data from trials suggests that pre-operative use is more effective, a significant proportion treated with radiotherapy in Ireland receive it post-operatively rather than pre-operatively [
31]. These observations raise the possibility that underuse of radiotherapy, particularly preoperative radiotherapy, may be a contributor to rectal cancer mortality trends. Moreover, while the current study found that radiotherapy use was continuing to rise, any impact of this on mortality rates will not be seen for several years.
In terms of surgery, evidence-based guidelines have been published in Ireland aimed at standardising surgical management of rectal cancer [
30]. An audit of all rectal cancers diagnosed in 2007 found that, while guidelines were in place, best practice was frequently not adhered to [
35]. Surgery for rectal cancer can result in significant morbidity if undertaken without appropriate and accurate pre-operative staging. Accurate localisation of the tumour [
36‐
38], use of MRI (magnetic resonance imaging) [
39] and ERUS (Endo-rectal ultrasound) [
40‐
42] as diagnostic tools, and recording of accurate pre-operative histological data [
43,
44], are all essential for successful treatment. However the national audit revealed that there were often inadequate investigations and/or recording of such data [
35]. In addition while multi-disciplinary meetings (MDM) have been shown to improve outcomes for rectal cancer [
45,
46], treatment options were only discussed at MDMs for around half of patients. Moreover patients treated at low volume centres were less likely to be discussed at MDMs and to have neo-adjuvant therapy [
35]. Further evidence suggests that comorbidity, rather than age, in elderly rectal cancer patients increases risk of death after surgery [
47]. Therefore age alone should not dictate the use of restorative rectal resection [
47]. However, our analyses indicate lower use of surgery in elderly than younger patients (≥75; 81%; <75: 92-99%) as well as larger increases in age standardised mortality in those aged 70 and older [
13]. These observations, combined with likely under use of best practice, may provide a possible explanation for the observed trends in mortality.
Biennial FIT-based screening in the 55-74 age group in Ireland could reduce colorectal cancers deaths in the population from as early as the second year of the programme [
10]. However, as noted earlier, screening is being introduced in those aged 60-69, suggesting that it is likely to take some considerable time to have any impact on the trends in rectal cancer mortality reported here.