Colorectal cancer

Introduction: population screening for colorectal cancer

From Cancer Guidelines Wiki

Background[edit source]

Colorectal cancer is an exemplar disease for population screening. It is one of only three cancers – the others being cancers of the female breast and the cervix – which satisfies all 10 of the World Health Organization’s principles of screening:[1]

  1. It is an important health problem.[2]
  2. There is a recognisable latent or early symptomatic stage.
  3. Its biology is generally well understood.
  4. There should be an accepted treatment for patients with recognised disease.
  5. Effective and accurate screening tests are available.
  6. The screening test is considered acceptable to the population.
  7. There is agreement on who should be screened.
  8. Facilities for diagnosis and treatment are available.
  9. There is an economically balanced case for screening in relation to expenditure on healthcare as a whole.[3]
  10. Screening is a continuous process.[1]

Colorectal cancer screening is primarily directed at middle-aged people in good general health, with no symptoms that might indicate colorectal cancer. Invitations to participate in screening, therefore, should encourage invitees with colorectal cancer symptoms to consult a GP rather than undergo a screening test.

Ideally, centrally organised population programs should take responsibility for identification of those eligible for screening, choice of screening test, the invitation process, provision of screening at no cost to participants, documentation of follow-up investigations, and evaluation of outcomes and cost-effectiveness, as well as assessment of the quality of each step in the screening pathway.[4][5][6][7] Screening for colorectal cancer now has widespread acceptance at an international level, although local circumstances affect program design and choice of screening test.[8] Many national programs, especially those in Europe, Canada and Australasia, utilise organised population screening rather than opportunistic approaches.[9]

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Colorectal cancer screening in Australia[edit source]

In 1997, the Australian Health Technology Advisory Committee (AHTAC) reviewed the evidence on screening and recommended that Australia should develop a program for the introduction of population screening for colorectal cancer by faecal occult blood testing for the average-risk population (well population aged over 50 years).[10] A pilot study conducted in three regions (2002–2004) indicated that a national program in Australia would meet the criteria of the Australian Cancer Screening Framework and was likely to be well accepted by health professionals and the recommended screening cohort.[11]

The Australian Government introduced the National Bowel Cancer Screening Program (NBCSP) in 2006, with a mail-out of immunochemical faecal occult blood test (iFOBT, also known as faecal immunochemical tests or FITs) kits to Australians turning 55 and 65 from August that year. This marked the commencement of an incremental roll-out, expanding the program as capacity increased and working towards coverage of the 50–74 years age group by 2020 (see Table 3.1).[12]

The key elements of the NBCSP are:[12]

  • the use of iFOBT as the screening test
  • provision of iFOBT screening at no cost to participants
  • distribution of invitations and screening tests by mail
  • analysis of screening in a central laboratory
  • follow-up of positive test results, mostly by colonoscopy, through the usual care pathway backed up by a central reminder service
  • central collation of data and reporting of NBCSP outcomes via regular reports.

See the NBCSP participant’s screening pathway.

Table 3.1 Australian National Bowel Cancer Screening Program target populations in 2006–2019[edit source]
Period Target ages
2006–2008 55 and 65
2008–2013 50, 55 and 65
2013–2014 50, 55, 60 and 65
2015 50, 55, 60, 65, 70 and 74
2016 50, 55, 60, 64, 65, 70, 72 and 74
2017 50, 54, 55, 58, 60, 64, 68, 70, 72, 74
2018 50, 54, 58, 60, 62, 64, 66, 68, 70, 72, 74
2019 onward 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74

Source: Australian Institute of Health and Welfare[12]

Extensive published research has shown that the NBCSP, even in its incomplete form, is having a significant impact on reducing colorectal cancer burden. Key findings include:

  • a favourable shift in pathological stage in screen-detected cancers [13][14][15]
  • modelling studies supporting both marked cost-effectiveness[16] and a considerable impact on colorectal cancer mortality[17]
  • data linkage studies demonstrating that NBCSP invitees, especially those who participated in the program, have a lower risk of dying from colorectal cancer.[15][18]

Screening infrastructure in the NBCSP is being progressively strengthened to improve its efficiency and effectiveness. Recent initiatives include the development of a new, interactive central register (the National Cancer Screening Register [NCSR]), public awareness campaigns and measures to boost training and quality of colonoscopy. On current evidence, the most significant barrier to improved program effectiveness is the relatively low participation rate (37% of all invitees at December 2014).[19]

There is, as a matter of course, a requirement to continually review screening policy (screening test, interval, pathway, cohort, etc.) for optimal population benefit as new evidence is published. In 2015 the Australian Commonwealth Department of Health commissioned a review of national guidelines for population screening for colorectal cancer, as part of the revision of the 2005 NHMRC-approved Clinical practice guidelines for the prevention, early detection and management of colorectal cancer.[20]

This revision of population screening guidelines provides a review of up-to-date evidence relating to the effectiveness, acceptability, feasibility and cost-effectiveness of a range of currently available screening methods. The review also examines starting and stopping ages for population screening and the frequency with which screening tests should be offered to the target population. In addition to systematic reviews of published clinical evidence, modelling studies were commissioned to evaluate the cost-effectiveness of alternate technology options for screening and the optimal target age range.

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Screening benefit[edit source]

The primary aims of colorectal cancer screening are to reduce the morbidity and mortality of the disease through (1) earlier detection of cancer and (2) prevention of cancer through detection and removal of pre-malignant adenomas.[20] Such screening can be provided on an individual basis (opportunistic screening) or for populations through centrally organised programs.

Opportunistic screening has been adopted as the preferred approach in some health settings, particularly in the USA.[21][22] However, centrally organised screening is designed to promote participation within the target population, irrespective of social determinants of health such as income, level of education, language spoken or geographic location.[4] This potentially increases the impact on colorectal cancer morbidity and mortality as well as providing more equitable health care for the population. Other advantages of organised screening include more efficient and cost-effective use of resources and the ability to systematically address quality assurance throughout the screening pathway.

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Screening test accuracy[edit source]

There are a number of tests designed to detect signs of colorectal cancer in asymptomatic patients, with differing performance, costs, acceptability and risks.[10] These include:

  • faecal tests – faecal occult blood tests (FOBTs) to detect bleeding arising from cancers or adenomas, or newer technologies involving detection of DNA mutations shed by cancer (faecal DNA test)
  • endoscopic tests to directly visualise mucosal abnormalities (flexible sigmoidoscopy, colonoscopy)
  • computed tomography (CT) colonography to detect anatomical abnormalities with x-ray
  • plasma tests to detect cancer biomarkers.

There are two types of FOBTs:[23][24]

  • immunochemical FOBTs (iFOBTs), which directly detect haemoglobin, using antibodies specific for the globin moiety of human haemoglobin (used by the NBCSP since its onset)
  • guaiac FOBTs (gFOBTs) detect peroxidase activity, an indirect method for identification of haemoglobin.

During the 1990s, randomised controlled trials (RCTs) performed in Minnesota (USA), Nottingham (UK) and Funen (Denmark) showed that FOBTs were an effective method of screening for colorectal cancer.[25][26][27][28][29] Subsequent meta-analyses provided Level I evidence for a 15–30% reduction in mortality.[30][31] High-level evidence for effectiveness has now become available for one-time flexible sigmoidoscopy,[32][33][34][35] with reductions in colorectal cancer-related mortality. However, the other modalities have yet to undergo comparable trials and thus the evidence base to support effectiveness relies primarily on observational data. Three RCTs to evaluate colonoscopy are currently in progress.[36][37][38]

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The balance of benefits, harms and cost-effectiveness[edit source]

To achieve its primary aim of reducing cancer-related mortality, a population-based cancer screening program must be acceptable to the target population, feasible within the overall system for delivery of health care, and have an acceptable level of cost-effectiveness.

A recent comparative modelling evaluation conducted on behalf of the US Preventive Services Task Force used life–years gained as a measurement of effectiveness and the estimated number of colonoscopies as a measurement of burden to compare colorectal cancer screening strategies using eight different screening test technologies.[21] Under the assumption of 100% screening adherence in each case, the evaluation found that, in the US context, the strategies providing the best balance of benefits to harms would be 10-yearly colonoscopy screening, 10-yearly flexible sigmoidoscopy screening combined with annual iFOBT, 5-yearly CTC screening, and yearly iFOBT alone for screening for ages 50–74 years. However, the study did not report on the impact of more realistic adherence assumptions (which could be expected to differ by screening modality and frequency) on either benefits or harms. Furthermore, the cost-effectiveness of the alternative strategies was not considered.

The comparative benefits, harms and cost-effectiveness of the NBCSP in Australia have recently been estimated compared to other potential future alternative or adjunctive options for screening in Australia.[39] A modelling study was therefore conducted to evaluate the health benefits, harms, and cost-effectiveness of colorectal cancer screening with iFOBT versus flexible sigmoidoscopy, colonoscopy, CTC, faecal DNA and plasma biomarkers.

The modelling is described in detail in the Technical report.

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Screening age[edit source]

The early RCTs on gFOBT-based screening showed benefit for people aged 45–50 years and older.[40][41][42][43][25][28][29][26][27] Cost-effectiveness studies also demonstrate that the age range for screening influences cost-effectiveness. [12] The risk of colorectal cancer increases with age, as shown in Table 3.2. The observation that 10-year risk increases 4-fold between ages of 40 and 50 years has led to the recommendation that screening of average risk people should commence at age 50 years, a recommendation that is consistent with the deliberations of several major international bodies.[12][13][14][15][16][17]

The recently published US Preventive Services Task Force guidelines endorsed 50 years as the starting age for screening and found convincing evidence showing that screening from 50 to 75 years of age reduces mortality from colorectal cancer.[22] They observed a diminishing benefit and a greater risk of adverse events after age 75.

When complete in 2020, the NBCSP will invite the general population aged 50 to 74 to screen. The starting age was based on the low age-specific incidence of colorectal cancer in those below 50 years of age and concern that the risk with follow-up colonoscopy (including the small risk of death from colonoscopy) is much closer to the low risk of colorectal cancer and its mortality in those less than 50.[44]

This review re-examines evidence on the appropriate age range for screening, prompted by suggestions of an increase in risk for colorectal cancer in younger people and the longer life expectancy for the elderly.

A detailed modelled analysis has also been undertaken to quantify the benefits, harms and cost-effectiveness of extending the age range for screening in the Australian context. This analysis concluded that continuing to screen at a population level was no longer cost-effective in people over the age of 74 years (due to the competing mortality risk). For younger people, the analysis found that starting screening at age 45 years could be cost-effective, but the ratio of benefits to harms, expressed as the number-needed-to-colonoscope (NNC) for each death prevented, was far less favourable than when screening people aged 50–74 years. For the existing NBCSP, the estimated NNC is 56 colonoscopies for each death prevented in the program (in a perfectly adherent cohort); thus this is the existing benchmark. For a program starting screening at age 45 years (but still finishing at 74 years), the NNC for each death prevented would be increased to 71 colonoscopies per death prevented (in a perfectly adherent cohort). This is a substantial increase in the NNC over the entire lifetime of those eligible for, and participating in, screening, given that the difference in the period of eligibility is only 5 years.

Table 3.2. Absolute risk of colorectal cancer[edit source]
If a person is aged Risk of colorectal cancer over the next 10 years
Men Women
30 0.074% 1 in 1350 0.072% 1 in 1390
40 0.32% 1 in 313 0.27% 1 in 370
50 1.15% 1 in 87 0.80% 1 in 125
60 2.79% 1 in 36 1.74% 1 in 57
70 4.57% 1 in 22 2.90% 1 in 34

Absolute risk is the observed or calculated probability of the occurrence of colorectal cancer in a population. These risks were calculated from the Australian Institute of Health and Welfare[44] national colorectal cancer incidence data for the year 2000, which included some of the highest incidence in recent years and was prior to roll-out of the National Bowel Cancer Screening Program (NBCSP).

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References[edit source]

  1. 1.0 1.1 Wilson J, Junger G. Principles and practices of screening for disease. Geneva, Switzerland; 1968. Report No.: 34.
  2. Gnauck R. World Health Organization for screening In: David Schottenfeld, Paul Sherlock, Sidney J. Winawer. Colorectal Cancer: Prevention, Epidemiology and Screening New York: Raven Press; 1980.
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Appendices[edit source]

View NHMRC Evidence statement form PSC1a NHMRC Evidence statement form PSC1a

View NHMRC Evidence statement form PSC1b NHMRC Evidence statement form PSC1b