Colorectal Cancer: Open Access

Keywords

Colonoscopy; Colorectal cancer; Screening

Introduction

Inspired by pioneer studies on screening for colorectal cancer (CRC) [1-3], a large scale feasibility study was carried out from 2005 to 2006 in two Danish counties [4]. Based upon experiences from that study and European guidelines [5], a national screening programme for CRC was launched in Denmark in March 2014. Citizens between 50 and 74 years of age are invited to participate by submitting a faecal sample, which is examined by i-FOBT (immunochemical faecal occult blood test) at a regional centre. Citizens with a positive i-FOBT are subsequently referred for colonoscopy at one of four regional endoscopy units, one of which is the Endoscopy Unit of Herning Regional Hospital. In this study we report the findings of screening colonoscopies during the first year of the new national screening programme.

Materials and Methods

All citizens who had a screening colonoscopy performed at our Endoscopy Unit during the first 12 months of the national screening programme entered the study. Colonoscopy was performed as an outpatient procedure with or without Propofol or Midazolam sedation according to preference of the citizen and/or the endoscopist and after mutual agreement of the course of action. Details of the colonoscopies and findings at the procedures were recorded prospectively as well as the results of the related histopathological examinations. At the end of the study period relevant diagnostic codes were sought in the hospital’s electronic databases to identify any patient admitted to the hospital for complications related to the screening colonoscopy.

All detected adenocarcinomas were treated according to national guidelines for treatment of CRC [6], and the stage of cancers (UICC-classification) found by screening was compared (χ²- test) with the stage of adenocarcinomas found in symptomatic patients referred to our department during the same period of time.

Detected polyps were removed. Adenomatous polyps were histologically divided into low or high grade dysplasia polyps. However, not only the grade of dysplasia, but also the size and number of adenomas removed and the histological type of these indicate the risk of future malignancy and thereby determine scheduled follow up in the individual patient [5] (Table 1).

Table 1: Classification of adenomas and recommended surveillance following adenoma removal.

Before implementing the screening programme in the endocopy units, estimates were made [7] by the screening authorities as to predict various key point outcome measures (Table 2) in relation to screening colonoscopy. These estimates were based on results from the feasibility study [4], two recent Dutch studies using i-FOBT [8,9] and recommendations from the National Health Authorities [10]. At the end of the first year of screening colonoscopy the estimated / expected outcome was compared with what was in fact observed.

Table 2: Estimated and observed key point data during the first year of screening colonoscopy.

Results

Screening colonoscopy was performed in 905 citizens with a positive i-FOBT. In five cases (0.6%) a complete colonoscopy could not be performed and a CT-colonography was added in these cases, preferably on the same day. No perforations were seen, but 2 patients (0.2%) were admitted to the hospital with bleeding after polypectomy. Neither of these required surgery, in one patient the bleeding ceased spontaneously and in the other patient endoscopic haemostasis was achieved.

Table 2 shows the estimated and observed key point outcome measures. The rate of positive i-FOBT was 25% higher than estimated causing a larger number of colonoscopies performed than expected. Also, more citizens with positive i-FOBT turned up for colonoscopy than expected. Detected adenocarcinomas were fewer than expected, but the number of patients with polyps was greater than estimated, and more patients were scheduled for later endoscopic follow up than expected.

Cancer

Cancer was found in 71 citizens (7.8%). Of these 70 had adenocarcinoma, one of whom had two synchronous carcinomas. One citizen had a malignant neuroendocrine tumor. 36 citizens (51.4%) had adenocarcinoma Stage I (inclusive of adenocarcinoma in polyps), 12 (17.1%) had adenocarcinoma Stage II, 19 (27.1%) had adenocarcinoma Stage III and 3 (4.3%) had adenocarcinoma Stage IV (distant metastases). This distribution of stages is statistically highly significantly different (χ²=46.7, p<0.0001) from the distribution of stages in symptomatic patients diagnosed with CRC during the same period of time (Table 3).

Table 3: Total number of patients diagnosed with CRC in the Department of Surgery, Herning Regional Hospital, during the first year of screening colonoscopies. The distribution of stages is significantly different (p<0.0001) between cancers diagnosed by screening and in patients with symptoms.

Adenomas

In 482 (53.3%) of the citizens adenomatous polyps were detected and removed, in the individual ranging from 1 to 37 polyps. Of these 77 (16%) had one or more adenomas with high grade dysplasia. Risk classification and the scheduled follow up is shown in Table 4. Intermediate or high risk polyps were found in 63.1% of those with polyps, and they were consequently scheduled for a later follow up endoscopy. In 13 patients (2.7% of patients with adenoma) the adenoma was either too large or located in such an awkward position that endoscopic removal was considered impossible, and these patients had an operation (11 right hemicolectomy, 1 sigmoid resection, 1 TEM (transanal endoscopic microsurgery).

Table 4: Risk classification of 482 patients with adenomatous polyps.

Discussion

The incidence rate for CRC in Denmark is high and CRC is a significant public health burden. The officially declared purpose of the national screening programme for CRC is to lower the stage of cancers diagnosed and to reduce future incidence of CRC by removing detected adenomas [10]. A possible effect of the latter will show in 5 to 10 years, whereas the former purpose is clearly evident by now as seen in Table 3. At colonoscopy we found cancer in 7.8% of citizens with a positive i-FOBT, which is a little less than the expected 9% [4,7], and we observed a significantly larger number of patients with low stage cancer and significantly lower number of patients with high stage cancer than found in patients referred to our department with symptomatic cancer. This observed distribution of stages is compatible with those of previous randomised trials done in research settings [2,3,11,12] and in population-based first round screening programmes [13,14], whereas the observed detection rate of cancer and adenomas in the present study is higher than in these studies. This might be explained by the fact, that Guaiac based FOBT (g-FOBT) was used in the mentioned studies, while i-FOBT is used in the Danish national screening programme. It has been demonstrated that using i-FOBT in population-based screening for CRC has superior detection rates (higher sensitivity) compared to g-FOBT screening [8,9,15]. Our observations are compatible with the findings of other screening studies using the i-FOBT [8,9].

One of the concerns in relation to implementing the national screening programme has been the risk of complications to colonoscopy. In a recent survey of literature on screening colonoscopy the risk of perforation and bleeding was found low and without mortality [16]. Six relevant studies published from 2000 to 2006 were identified and reviewed, and the risk of perforation varied from 0% to 0.24% and the risk of bleeding from 0% to 0.3%. In our first year of screening colonoscopy we had no perforations and 0.2% of patients with bleeding after polypectomy, which is considered acceptable.

The introduction of the national screening programme has added a greater workload to our endoscopy unit than expected as more than 25% more citizens have been referred for colonoscopy than estimated (Table 2). The number of needed screening colonoscopies is determined by the number of i-FOBT positive faecal samples, which in turn is influenced by the chosen cut off value set to categorize the test as positive or negative. If the cut off value is too low, many unnecessary colonoscopies will be performed, and if it is too high a number of adenomas and even cancers will be missed and probably show up later as interval cancers between screening rounds. This dilemma will undoubtedly be addressed by the national screening authorities, as will evaluation of the rapidly evolving evidence regarding other CRC screening tests (flexible sigmoidoscopy, CT-colonography, faecal DNA test), but it is beyond the scope of the present study to discuss these issues.

Unforeseen screening colonoscopies have turned out to be more time consuming on average than other colonoscopies due to a great number of citizens with polyps (53.3%) that have to be removed. This in combination with the finding of intermediate or high risk polyps causing future scheduled endoscopic follow up in almost 50% more citizens than expected will further add to the workload of the endoscopy unit, and these observations have to be taken into account when planning the future capacity of our and other units for screening colonoscopy. On the other side, the high number of detected high and intermediate risk adenomas calls for action. A number of intervention studies have suggested that treatment with 75 mg aspirin can significantly reduce the occurrence of future high risk adenomas in such patients [17] and aspirin has also been shown to reduce the occurrence of later colorectal cancer in high-risk populations [18,19]. Based on these data with aspirin and the present data from the Danish colorectal screening program, we are now planning a medical intervention study with an aim to prevent occurrence of new adenomas or future CRC in high-risk adenoma patients.

References

1. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM,et al. (1993) Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 328:1365-1371.
2. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O (1996) Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 348:1467-1471.
3. Hardcastle JD, Chamberlain JO, Robeinson MHE, Moss SM, Amar SS, et al. (1996) Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.Lancet 348:1472-1477.
4. Screening for coloractel cancer in the Counties of Vejle and Copenhagen (2007) A transverse evaluation of a pilot project. Copenhagen: Research Centre for Prevention and Health.
5. European guidelines for quality assurance in colorectal cancer screening and diagnosis (2010) Bruxelles: European Commission.
6. https://dccg.dk/retningslinjer
7. Background note on the introduction of bowel cancer screening in Region Midtjylland (2012) Central Denmark Region, Department of Folk Studies.
8. van Rossum LG, van Rijn AF, Laheij RJ, van Oijen MG, Fockens P, et al. (2008) Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 135:82-90.
9. Hol L, van Leerdam ME, van Ballegooijen M, van Vuuren AJ, van Dekken H, et al. (2010) Screening for colorectal cancer; Randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. GUT59:62-68.
10. Recommendations relating screening for Colorectal Cancer (2012) Health.
11. Kewenter J, Brevinge H, Engaras B, Haglind E, Ahren C(1994) Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by faecal occult blood testing. Results for 68308 subjects. Scand J Gastroenterol 29:468-473.
12. Faivre J, Dancourt V, Lejeune C, Tazi MA, Lamour J, et al. (2004) Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study.Gastroenterology 126:1674-1680.
13. UK Colorectal Cancer Screening Pilot Group (2004) Results of the first round of a demonstration pilot of screening for colorectal cancer in the United Kingdom. BMJ.
14. Steele RJC, McClements PL, Libby G, Black R, Morton C, et al. (2009) Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer. GUT 58:530-535.
15. Van Rossum LG, van Rijn AF, van Munster IP, Jansen JB, Fockens P, et al. (2009) Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests.Neth J Med 67:182-186.
16. Holst LL, Andersen O, Fischer TK (2013) Low risk of complications of screening colonoscopy.pp:1852-1855.
17. Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, et al. (2009)Aspirin for the chemoprevention of colorectal adenomas: Meta-analysis of the randomiszed trials. J Natl Cancer Inst 101:256-266.
18. Friis S, Riis AH, Erichsen R, Baron JA, Sorensen HT (2015) Low-dose Aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk: A population-based, case-control study.Ann Intern Med 163:347-355.
19. Huang WK, Tu HT, See LC (2015) Aspirin use on incidence and mortality of gastrointestinal cancers: current state of epidemiological evidence. Curr Pharm Des, Sept 15.