CRC is both common and preventable. The challenge is the lack of symptoms preceding advanced disease.
In 2018, colorectal cancer (CRC) was the second most common cause of cancer death in Australia.
It was estimated to account for 11% of all cancer-related deaths in 2020. The risk of CRC diagnosis before age 85 remains one in 13 for Australian women and one in 10 for Australian men. (1)
CRC is a largely preventable with appropriate screening and surveillance. The theory being that the early identification and removal of pre-cancerous colonic polyps can prevent CRC by preventing the progression of adenoma to CRC. Alternatively, the identification of early CRC can reduce mortality, especially when combined with other factors such as advances in surgery and oncology.
However, to complicate the clinical challenge; while CRC is a common condition, there are a lack of symptoms or signs preceding advanced disease which speaks to the value of screening.
It is important to assess the risk of the individual being screened. The following discussion regarding screening options applies to average risk individuals in the Australian population. Special populations such as those people affected by familial cancer syndromes, familial polyposis and inflammatory bowel disease are not considered in this discussion.
The “best” method for screening depends on the perspective and framing of the question. A discussion of the various perspectives and rationales is included below. Detailed cost comparison is not discussed but can be found elsewhere. (2) The issue of maximising patient participation, while equally valid, is also not included in this article.
Broadly speaking the methods of detection can be divided into invasive and non-invasive screening tests.
NON-INVASIVE OPTIONS
Faecal occult blood testing (FOBT)
FOBT is the most common, well-established non-invasive method of screening. The current version of FOBT uses an immunohistochemical method to detect small amounts of intact human haemoglobin in the faeces. The cut off value is set by various diagnostic accuracy studies to maximise sensitivity. Previous iterations of FOBT utilised a chemical reaction (guaiac test) which detected the peroxidase activity of heme, this reaction has significant overlap with non-human blood sources. This problem is largely eliminated with current immunohistochemical testing.
It is important to consider some of the factors associated with the aetiology of CRC when evaluating the ability of each test to detect this cancer, in particularly the precursors to advanced disease (adenomas). CRC develops through different pathways.
In patients aged over 50, two thirds of cases of develop through a conventional pathway (colonic adenomata), however one third will start as a sessile serrated lesion (SSL). This serrated pathway is important, especially in right sided CRC.
FOBT is considered less sensitive to SSL detection than other types of adenomas. (3) The low sensitivity of FOBT for SSL detection may be related to be a number of factors, including the thicker and more diffuse vasculature of the SSL which is thought to make it less likely to bleed as a result of friction: the proximal colonic location of SSLs which may decrease the blood in the stool as it travels to the distal colon, and the non-polypoid morphology of SSLs, which excludes the possibility of torsion of the polyp stalk, a cause of polyp blood loss. (3)
There are other issues to consider with non-invasive methods of screening.
FOBT in any form has the risk of false negatives, i.e. no blood is detected but a significant lesion is present. FOBT is more effective in detecting advanced lesions (cancer and highly dysplastic adenomas) than early lesions. As mentioned, SSLs and lesions in the right-sided ascending colon are more likely to be missed by FOBT screening.
False positives must also be considered, i.e. blood is detected but no significant lesion exists. In this situation the current generation of immunohistochemical testing performs better with less susceptibility to environmental pollutants (meat and vegetables that mimic haeme) than the guaiac-based tests. However, a positive result due to benign processes such as colonic angioectasia, diverticular disease and anorectal disorders is still common.
It is also likely that a fair proportion of patients who are being directed to have FOBT will also be taking antiplatelet or anticoagulant therapy, which will increase the rate of FOBT positivity.
A positive FOBT is considered to increase the yield of colonoscopy for the detection of CRC and advanced adenomas, relative to a screening colonoscopy, in which cancer and advanced neoplasia are detected much less frequently. (4)
Before ordering an FOBT, consider:
1. Does the patient have gastrointestinal symptoms or PR bleeding? If so a diagnostic test such as colonoscopy is required. A screening tool is no longer appropriate.
2. Is there a known process, medication or condition that may limit the reliability of FOBT for screening? if so, a definitive test,such as colonoscopy is more appropriate.
INVASIVE OPTIONS
Colonoscopy
Some confusion exists regarding colonoscopy as a screening test. This is because colonoscopy has utility as both a screening AND diagnostic modality. Colonoscopy is currently considered the gold standard for the detection of colonic polyps. It should be noted that it is not a perfect test and there is a wide variation among individual endoscopists in rates of polyp detection, especially the detection of sessile serrated lesions.
Combined with detection, colonoscopy offers the opportunity for therapy with endoscopic means.
Colonoscopy, while having the greatest sensitivity for early pre-cancerous adenomas, also carries procedural and anaesthetic risks. These are generally considered to be less than one in 1000 for routine screening colonoscopy.
Colonoscopy also requires patient participation in the essential component of a successful procedure which is the bowel preparation.
Colonoscopy is also user-dependent. There is the potential to falsely reassure patients that lesions don’t exist when in fact they have been missed by the proceduralist (the low adenoma detectors paradox). While for some, there is an increased burden of surveillance for patients in whom low-risk lesions are discovered (high adenoma detectors paradox).
Flexible sigmoidoscopy
Sigmoidoscopy involves partial examination of the bowel yet incurs most of the risks of colonoscopy and fails to examine the right side of the colon. Its advantage is that it doesn’t require oral bowel preparation. This is not an ideal screening modality for the patient at average risk of colorectal cancer.
Imaging
While imaging has previously been touted as a method for screening, it lacks the ability to detect sessile lesions with accuracy. Combined with the preparation required to complete CT colonography, the ionising radiation exposure and the lack of therapeutic options this method is not considered a first-line screening option for the average risk patient.
SURVEILLANCE
How does surveillance differ between the non-invasive and invasive CRC screening options? In general, if polyps are detected at colonoscopy then patient risk should be determined by these, and regular surveillance endoscopic evaluation scheduled at the recommended intervals (guideline).
Importantly, there is no current recommendation for regular CRC screening that combines surveillance colonoscopy and concurrent FOBT testing. One method should be chosen and stuck with. The reasoning here is that if a schedule for regular colonoscopy is followed then the risk of interval CRC is low. Adding FOBT testing in between procedures is unnecessary and may shorten the interval between colonoscopies without evidence of patient benefit, increasing the risk of potential harms and increasing health care costs.
Some confusion remains over the use of FOBT in post-polypectomy surveillance. Once a diagnostic test has been undertaken and treatment completed (polyps removed) patients require regular endoscopic monitoring rather than FOBT screening in most circumstances.
The most recent Australian guidelines allow low risk patients (as defined by history and endoscopic findings) to exit an endoscopic surveillance approach at four years and revert to FOBT testing.
Once a patient is under endoscopic surveillance the FOBT no longer plays a role. Ideally, patients should be reminded of this as they will continue to receive the government FOBT packs automatically.
Dr Stuart Kostalas is a gastroenterologist practising in Port Macquarie in NSW. He has post graduate degrees in clinical epidemiology and medical statistics. He has a clinical interest in high quality endoscopy for both screening, surveillance and therapy. His primary research interest is sessile serrated lesions. He is a senior lecturer at UNSW rural clinical school.
References:
1. https://www.canceraustralia.gov.au/affected-cancer/cancer-types/bowel-cancer/bowel-cancer-colorectal-cancer-australia-statistics.
2. https://www.aihw.gov.au/getmedia/da6be503-6185-4b05-9724-953f81ad31de/aihw-can-133_31July2020.pdf.aspx?inline=true
3. Chang LC, Shun CT, Hsu WF, Tu CH, Tsai PY, et al. Fecal Immunochemical Test Detects Sessile Serrated Adenomas and Polyps With a Low Level of Sensitivity. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017;15(6):872-9 e1.
4. Robertson DJ, Lee JK, Boland CR, Dominitz JA, Giardiello FM, et al. Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2017 Apr;152(5):1217-1237.e3.
