Clinical
Volume 47, No. 12, December 2018

Colorectal cancer screening in Australia: An update

Cameron J Parkin    Stephen W Bell    Naseem Mirbagheri   
|   Cite this article    BIBTEX    REFER    RIS    |

Background
Colorectal cancer is the second most common cancer in Australia. The National Health and Medical Research Council (NHMRC) has introduced new recommendations for the prevention, early detection and management of colorectal cancer. General practitioners play a key part in the advocacy, risk stratification and implementation of colorectal cancer screening on the basis of a patient’s individual risk.
Objective
The aim of this paper is to summarise the NHMRC recommendations pertaining to screening so that they may be applied in general practice.
Discussion
The recommended strategy for population screening in Australia remains the immunochemical faecal occult blood test, commencing at age 50 years in asymptomatic individuals with no family history of colorectal cancer. This test is to be performed every two years to age 74 years. Individuals with a family history of colorectal cancer will need appropriate risk stratification. Aspirin should now be considered for all patients aged 50–70 years in the prevention of colorectal cancer.
 

Colorectal cancer (CRC) is the second most common cancer, after breast cancer, in Australia.1 After lung cancer, it is the second most common cause of cancer death.1 Statistics from the Australian Institute of Health and Welfare (AIHW) estimate that in 2018, 17,004 new cases of CRC will be diagnosed.1

It is well established that CRC has a precancerous stage in the form of a polyp, which acquires mutations through one of three molecular pathways to become an invasive lesion.2 These molecular pathways include the conventional adenoma–carcinoma sequence (APC gene mutation),2 the serrated pathway (KRAS and BRAF mutations) and the familial pathways (eg Lynch syndrome and familial adenomatous polyposis).3 The objective of screening in CRC is to identify individuals who have a higher risk of harbouring a polyp or early cancer (via detection of blood in stool) and thus to remove precancerous lesions (ie polyps) or early cancer in order to stage-shift cancer detection to less advanced stages, and thus reduce mortality. Given this pathophysiological process, the screening of CRC remains one of the most effective screening methods available for detecting cancer.4

Tools used to screen for colorectal cancer

The current guidelines suggest using a faecal occult blood test (FOBT), which aims to identify microscopic blood in the stool, as the first-line screening test to detect CRC. There are two forms of the test: the guiac-based form (gFOBT) and the immunochemical form (iFOBT). The gFOBT identifies haemoglobin in the stool through a peroxidase reaction of the haem component of haemoglobin.5 Importantly, this reaction is not limited just to human haem, and can be positive following the ingestion of red meats.5 The iFOBT uses an antibody reaction to specifically identify the human haemoglobin.5 Since the gFOBT is not as specific as the iFOBT, diet and medication modifications, such as avoiding red meat, vitamin C and anti-inflammatories, are required three to five days prior to testing.5 As such, iFOBT is the preferred test. In patients who have macroscopic blood loss, a referral for colonoscopy should be undertaken without using FOBT. Other screening tests, such as multi-targeted DNA stool testing, flexible sigmoidoscopy and colonoscopy, are also available but are not part of the current screening program because of cost, resource limitations and risks associated with invasive procedures.6

Evidence for the screening of colorectal cancer

One of the earliest sources of evidence highlighting the benefits of CRC screening was published in the New England Journal of Medicine in 1993, when a study cohort of 46,551 participants aged 50–80 years was assigned to annual gFOBT, biennial gFOBT or a control group.7 Through the use of gFOBT, it was found that the 13-year cumulative mortality from colorectal cancer was reduced by 33%.7 A recent systematic review and meta-analysis by Fitzpatrick-Lewis et al8 in 2016 comparing screening through gFOBT, iFOBT, flexible sigmoidoscopy and colonoscopy showed no difference in all-cause mortality between the screening methods. The pooled results from the four randomised studies using gFOBT compared with controls showed an 18% reduction in disease-specific mortality with a median follow-up of 18.25 years.8 The results from the only randomised controlled trial (RCT) available using iFOBT showed no difference in mortality, although the length of follow-up was only six years, much shorter than the 10-year interval expected for screening results to show benefit.8

Studies have also characterised the rates of detection of advanced colorectal adenoma and early and advanced CRC using the iFOBT in average-risk populations. A Japanese study in 2010 examined the detection rates of iFOBT in 700 patients who were undergoing concurrent screening with a colonoscopy.9 Patients were deemed to be at average risk of developing CRC. The sensitivity of the iFOBT in being able to detect pre‑cancerous adenomas was 33.9%, and specificity was 90.6%.9 In detecting early stage CRC, the sensitivity was 84.6% and specificity was 89.8%9. In advanced CRC, the sensitivity was 43.7% and specificity 91.9%9.

The National Bowel Cancer Screening Program

The National Bowel Cancer Screening Program (NBCSP) was introduced in 2006. By 2020, all Australians aged 50–74 years will be offered screening every two years. While the iFOBT is mailed out to patients as part of the program, general practitioners (GPs) can request these tests for patients who have missed out. The AIHW has recently released a report on the national screening (Box 1).10
 

Box 1. Summary of the Australian Institute of Health and Welfare’s national report on bowel cancer screening for 201710
  • A total of 2.6 million people were invited to participate between 2014 and 2015
  • There was a 39% participation rate
  • Re-participation rate for those who had previously taken part and were receiving a subsequent screening invitation was 76%
  • In 2015, 41,000 of the population screened had a positive faecal occult blood test (FOBT) – 8% positivity rate
  • Of those with a positive test, 70% had follow-up investigation with the median time interval of 53 days
  • Of the patients with positive FOBT, 58% will have normal colonoscopy, 39% will be diagnosed with a polyp and only 3% will be diagnosed with cancer or suspected cancer
  • Risk factors for positive FOBT screening included: male gender, first screening, older ages, remote communities, low socioeconomic status and Aboriginal or Torres Strait Islander  background
  • Similarly, individuals are less likely to participate if they are young; have an Aboriginal or Torres Strait Islander ancestry, non–English speaking background, male gender or low socioeconomic status; or live in remote regions

Data linkage studies have shown a reduction in both mortality and morbidity associated with CRC since the introduction of screening.11 This trend of improved outcomes is only partly attributed to screening, as the decline predated the introduction of national screening and the magnitude of change is much more than would be expected with screening alone. Welch et al12 suggested three possible explanations:

  • improved surgical techniques, standardisation of preoperative and postoperative care and, importantly, the addition of adjuvant chemotherapy has improved survival
  • population education and bowel cancer awareness
  • healthier lifestyles and dietary changes.

Thus, it is important that GPs stipulate to patients that the best way to reduce mortality and, in particular, incidence (as there is no evidence that screening reduces incidence) is to adopt healthier lifestyles. This would include advising patients to reduce or cease smoking, limit alcohol intake, exercise regularly and consume a balanced diet.13

Recommendations

Updates in CRC screening guidelines

The current recommended strategy for population screening in Australia is an iFOBT every two years in asymptomatic individuals, starting from age 50 years to age 74 years.4 Extending the screening beyond the age of 74 years is not recommended as it is not cost-effective.4 In people aged 45–49 years who request screening after being fully informed of the advantages and harms of testing, an iFOBT every two years should be offered during the lead-up to their first routine invitations by the NBCSP at age 50 years.4 GPs have a vital role in identifying and advising individuals to opt out of the screening program if they have major comorbidities and limited life expectancy or if they have had a recent major illness or surgery. Several factors have been identified as barriers to FOBT uptake, including inconvenience, perceptions of handling faeces, fear of cancer diagnosis and cultural practices.14 GPs are crucial in addressing these modifiable factors and improving uptake of the screening program, which currently sits at 39%.10 As shown by Lew et al,15 at this current participation rate, the NBCSP is predicted to prevent 92,200 cancer cases and 59,000 cancer-related deaths over the period between 2015 and 2040.15 An additional 24,300 cancer cases and 37,300 deaths would be prevented if this participation rate was increased to 60%.15

Individuals who are symptomatic should not participate in the screening program but be referred directly for appropriate investigation. This also pertains to high-risk individuals such as those with recent history of colorectal cancer, chronic inflammatory bowel disease or certain high-risk genetic disorders.4 For patients who have had a recent high-quality colonoscopy (within two years), the current recommendation is that screening should be deferred for another two years.16 One positive iFOBT is adequate to refer for colonoscopy; repeating a positive FOBT is not recommended.16 Given patients’ fear of cancer diagnosis in the setting of a positive FOBT, it is often important to reassure this cohort that over 50% will have a normal colonoscopy.10

Risk and screening based on family history

Changes in risk stratification on the basis of family history are outlined in Table 1. It is important for health practitioners to investigate family history thoroughly to properly ascertain a patient’s risk. A family history of CRC is a significant risk factor for developing the disease.
 

Table 1. Risk stratification based on family history24
Category 1
(relative risk x 1–2)
Category 2
(relative risk x 3–6)
Category 3
(relative risk x 7–10)
Asymptomatic people who have:
  • no personal history of bowel cancer, colorectal adenomas, inflammatory bowel disease or family history of colorectal cancer (CRC)
OR
  • one first-degree relative with CRC diagnosed at 55  years or older
OR
  • one first-degree and one second-degree relative with CRC diagnosed at 55 years or older.
Asymptomatic people who have:
  • one first-degree relative with CRC diagnosed before age 55 years
OR
  • two first-degree relatives with CRC diagnosed at any age
OR
  • one first-degree relative and at least two second-degree relatives diagnosed with CRC at any age.
Asymptomatic people who have:
  • at least three first-degree or second-degree relatives with CRC, with at least one diagnosed before age 55 years
OR
  • at least three first-degree relatives with CRC diagnosed at any age.
 

The screening strategies for those at an increased risk of developing colorectal cancer have also changed.

Important changes include the age of commencing screening in patients with a family history and the recommendations for the use of aspirin. For all people aged 50–70 years, regardless of their risk of developing CRC, GPs should now actively consider commencing patients on low-dose aspirin (100–300 mg).17 There is level 1 evidence to suggest that regular consumption of aspirin can reduce incidence and mortality in CRC.18 Pooled analysis from RCTs has shown that daily aspirin use can reduce the occurrence of CRC by 24% and reduce CRC-associated mortality by 35% after 10 years of taking the drug.19 The mechanism by which aspirin to prevent the development of CRC is unknown. Aside from antiplatelet effects, it has been hypothesised that aspirin may be involved in altering tumorigenesis through the modulation of cyclooxygenase-2, which has an important role in cellular proliferation and angiogenesis.20,21 Additionally, aspirin is known to provide benefits in cardiovascular and neurovascular disease, as well as being cheap and readily accessible.

The safety profile of aspirin, given its widespread use, is reasonably well understood. The most serious adverse effects associated with regular aspirin use are gastrointestinal and intracranial bleeding. A meta-analysis of 35 RCTs found that a daily aspirin dose between 75 and 325 mg was associated with a hazard ratio for a major gastrointestinal bleed of 1.55 (95% confidence interval [CI]: 1.27, 1.90) in comparison to the placebo group.22 The risk of intracranial bleeding associated with low-dose aspirin has been shown to be lower than the risk of gastrointestinal bleeding but deemed significant because of its complications.23 Some, but importantly not all, studies have noted that higher doses have been associated with higher incidences and complications of gastrointestinal and intracranial bleeding. Further studies are needed to clarify the dose and duration of use for aspirin to be most effective. The current recommendation is that patients taking aspirin for prevention of CRC should do so for at least 2.5 years.17 There has been no evidence to suggest that a higher dose of aspirin, such as 600 mg, is more effective in reducing CRC mortality.17

Of relevance for general practice is that the recommendations for screening do not apply to patients who are symptomatic or who have a personal history of CRC. In such cases, referral to a specialist is advised.
 

Clinical Parkin Colorectal Screening Fig 1

Figure 1: Screening flowchart based on family history17,24,25

CT, computerised tomography; FDR, first-degree relative; iFOBT, immunochemical faecal occult blood test; RR, relative risk; SDR, second-degree relative


 

Table 2. Current screening guidelines based on family history17,24
Category 1 (relative risk x 1–2) Category 2 (relative risk x 3–6) Category 3 (relative risk x 7–10)
  • Immunochemical faecal occult blood test (iFOBT) should be considered every two years from age 45 years, given the risk of colorectal cancer at this age is approximately equivalent to the population risk at age 50 years
  • For patients aged 50–70 years, low-dose aspirin (100 mg) daily should be considered
  • iFOBT should be performed every two years from age 40 to 50 years
  • Colonoscopy should be performed every five years from age 50 to 74 years. Computed tomography (CT) colonography can be offered if colonoscopy is contraindicated
  • Low-dose (100 mg) aspirin daily should be considered
  • As a result of the possibility of Lynch syndrome, a complete family history should be taken and updated regularly, and the accuracy of the cancer diagnoses and polyp pathology should be checked carefully
  • Genetic testing is not appropriate at present for people with category 2 risk
  • iFOBT should be performed every two years from age 35 to 45 years
  • Five-yearly colonoscopy from age 45 to 74 years. CT colonography can be offered if colonoscopy is contraindicated
  • Low-dose (100 mg) aspirin daily should be considered
  • Referral to a genetic centre for hereditary cancer syndromes should be considered
 

Conclusion

CRC remains a huge health burden in Australia, and screening is vital in reducing mortality.4 The major limitation in the screening program is the low participation rate.10 GPs have a crucial role in the success of screening by facilitating participation in the screening program. Screening of patients with symptoms is inappropriate. Instead, these patients should be referred for investigation of their symptoms. Determining the patient’s risk, providing education, encouraging screening and instituting prompt referrals are essential in reducing CRC morbidity and mortality. The updated guidelines provide clear guidance regarding the current screening recommendations and suggest biennial screening between the ages of 50 and 74 years. The use of low-dose aspirin should now be discussed with all patients aged 50–70 years as a form of chemoprophylaxis. Individuals with a family history of CRC will need to start screening at an earlier age on the basis of category of risk. Further details regarding screening and management of CRC can be found on the Cancer Council Australia website (https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer).

Competing interests: None.
Provenance and peer review: Not commissioned, externally peer reviewed.
Funding: None.

References
  1. Australian Institute of Health and Welfare. Australian Cancer Incidence and Mortality books: Colorectal cancer. Canberra: AIHW, 2017. Available at www.aihw.gov.au/acim-books [Accessed 1 April 2018]. Search PubMed
  2. Snover DC, Jass JR, Fenoglio-Preiser C, Batts KP. Serrated polyps of the large intestine: A morphologic and molecular review of an evolving concept. Am J Clin Pathol 2005;124(3):380–91. Search PubMed
  3. Patel SG, Ahnen DJ. Familial colon cancer syndromes: An update of a rapidly evolving field. Curr Gastroenterol Rep 2012;14(5):428–38. doi: 10.1007/s11894-012-0280-6. Search PubMed
  4. St John J, Ee H, Canfell K, et al. Population screening for colorectal cancer. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Population_screening_for_colorectal_cancer [Accessed 10 December 2017]. Search PubMed
  5. Rabeneck L, Rumble RB, Thompson F, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012;26(3):131–47. Search PubMed
  6. Schreuders EH, Ruco A, Rabeneck L, et al. Colorectal cancer screening: A global overview of existing programmes. Gut 2015;64(10):1637–49. doi: 10.1136/gutjnl-2014-309086. Search PubMed
  7. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328(19):1365–71. Search PubMed
  8. Fitzpatrick-Lewis D, Ali MU, Warren R, Kenny M, Sherifali D, Raina P. Screening for colorectal cancer: A systematic review and meta-analysis. Clin Colorectal Cancer 2016;15(4):298–313. doi: 10.1016/j.clcc.2016.03.003. Search PubMed
  9. Park DI, Ryu S, Kim YH, et al. Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening. Am J Gastroenterol 2010;105(9):2017–25. doi: 10.1038/ajg.2010.179. Search PubMed
  10. Australian Institute of Health and Welfare. National Bowel Cancer Screening Program: Monitoring report 2017. Cat. no. CAN 103. Canberra: AIHW, 2017. Search PubMed
  11. Australian Institute of Health and Welfare. Analysis of bowel cancer outcomes for the National Bowel Cancer Screening Program. Cat. no. CAN 87. Canberra: AIHW, 2014. Search PubMed
  12. Welch HG, Robertson DJ. Colorectal cancer on the decline. N Engl J Med 2016;375(8):804. doi: 10.1056/NEJMc1608037. Search PubMed
  13. Macrae F, Lockett T, Clarke J, et al. Introduction: Primary prevention. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Primary_prevention [Accessed 10 December 2017]. Search PubMed
  14. Cole SR, Young GP, Esterman A, Cadd B, Morcom J. A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer. J Med Screen 2003;10(3):117–22. Search PubMed
  15. Lew JB, St John DJB, Xu XM, et al. Long term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: A modelling study. Lancet Public Health 2017;2(7):e331–40. doi: 10.1016/S2468-2667(17)30105-6. Search PubMed
  16. St John J, Ee H, Canfell K, et al. Population screening: Evidence summary and recommendations. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Population_screening_recommendations [Accessed 10 December 2017]. Search PubMed
  17. Macrae F, Clarke J, Emery J, et al. Chemopreventive candidate agents. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Clinical_question:Aspirin_for_prevention_of_colorectal_cancer [Accessed 10 December 2017]. Search PubMed
  18. Cao Y, Nishihara R, Wu K, et al. Population wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol 2016;2(6):762–69. doi: 10.1001/jamaoncol.2015.6396. Search PubMed
  19. Rothwell PM, Wilson M, Elwin CE, et al. Long term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741–50. doi: 10.1016/S0140-6736(10)61543-7. Search PubMed
  20. Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol 2012;9(5):259–67. doi: 10.1038/nrclinonc.2011.199. Search PubMed
  21. Chan AT, Arber N, Burn J, et al. Aspirin in the chemoprevention of colorectal neoplasia: An overview. Cancer Prev Res (Phila) 2012;5(2):164–78. doi: 10.1158/1940-6207.CAPR-11-0391. Search PubMed
  22. Lanas A, Wu P, Medin J, Mills EJ. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol 2011;9(9):762–68. doi: 10.1016/j.cgh.2011.05.020. Search PubMed
  23. Garcia-Albeniz X, Chan AT. Aspirin for the prevention of colorectal cancer. Best Pract Res Clin Gastroenterol 2011;25(4–5):461–72. doi: 10.1016/j.bpg.2011.10.015. Search PubMed
  24. Jenkins M, Lee-Bates B, Quakrim DA, et al. Colorectal cancer risk according to family history. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Clinical_question:Family_history_and_CRC_risk [Accessed 10 December 2017]. Search PubMed
  25. Jenkins M, Quakrim DA, Boussioutas A, et al. Screening strategies for people with a family history of colorectal cancer. Sydney: Cancer Council Australia, 2017. Available at https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Screening_based_on_family_history [Accessed 10 December 2017]. Search PubMed

Colorectal cancerScreening program

Download article