Modelled evaluation of screening age range

From Cancer Guidelines Wiki

Is population screening starting at an earlier age more effective and as feasible, acceptable and cost-effective as screening starting at age 50 years? In population screening, do the harms outweigh the benefits if routine screening is continued beyond the age of 75 years? (PSC1d)

Background

Randomised clinical trials[1][2][3][4][5][6][7][8] have demonstrated that population-based colorectal cancer screening reduces colorectal cancer mortality for average-risk individuals aged between 50–75 years.

To date, no population-based colorectal cancer screening trials have specifically reported the effectiveness for population screening in average-risk individuals under 50 years, or older than 75 years.

When RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. evidence cannot be obtained, modelling studies based on sophisticated understanding of colorectal cancer natural history are an acceptable source of data to guide public health planning decisions.[9][10][11][12][13]

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Modelling study findings

A modelled evaluation was undertaken to assess the benefit, harms and cost-effectiveness of colorectal cancer screening in people aged 50–74 years with iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. every 2 years (the strategy adopted by the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. program), in comparison with potential alternatives for the target age for colorectal cancer screening in Australia:

  • inviting people from age 40 or 45 years (versus 50 years)
  • continuing screening to age 79 or 84 years (versus 74 years)
  • a combination of these age ranges.

All strategies were evaluated for three scenarios with different screening adherence assumptions:

  • Scenario 1 assumed perfect adherence to recommendations for screening, follow-up and surveillance.
  • Scenario 2 assumed ‘high’ adherence (approximately 66–69% screening participation).
  • Scenario 3 assumed ‘low’ adherence (approximately 49% screening participation, derived from currently observed rate[14]).

Although Scenario 1 is not achievable in practice, this analysis allows direct comparison of the outcomes and costs of screening approaches independent of the differing (and uncertain) adherence assumptions for each new strategy. Scenarios 2 and 3 were selected in order to test the robustness of the study findings by evaluating strategies under realistic participation assumptions of imperfect adherence.

When the two realistic (imperfect) participation scenarios were considered, favourable assumptions were made with respect to screening participation in 40–49 year-olds and 75–84 year-olds (i.e. the screening participation rate among the 40–49 and 75–84 years age groups was assumed to be the same as the rate modelled for 50-year-olds and 74-year-olds, respectively, with no impact on screening behaviour at 50–74 years. As a result, strategies assuming an alternative screening age range were associated with a higher proportion of individuals being screened at least once in a lifetime compared to the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease., which may not be the case in practice (i.e. people screened in their forties may be, in practice, less likely to screen at older ages). These participation assumptions must therefore be considered in interpreting the result for realistic (imperfect) adherence), whereas the findings for perfectly adherent cohorts reflect the direct effects of screening age range per se.

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Health outcomes

With perfect adherence, the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. would reduce age-standardised risk (in 0-89 years) of colorectal cancer incidence by 52% and mortality by 74%, compared with no screening. Extending the target age group would result in additional, relatively modest benefits; extending screening to a younger age group (starting at 40 or 45 years) would result in additional reductions in incidence (4–6 percentage points) and mortality (4–8 percentage points). Similarly, extending screening to an older age-group (ending at 79 or 84 years) would result in an additional reductions in incidence (2 percentage points) and mortality (4–5 percentage points).

Compared with no screening, iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. screening every 2 years at age 50–74 years (the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease.) was predicted to:

  • reduce colorectal cancer incidence by 52% and reduce colorectal cancer mortality by 74% in Scenario 1 (perfect adherence)
  • reduce colorectal cancer incidence by 33% and reduce colorectal cancer mortality by 53% under Scenario 2 (‘high’ adherence)
  • reduce colorectal cancer incidence by 23% and reduce colorectal cancer mortality by 37% under Scenario 3 (‘low’ adherence).

Extending the target age group would result in additional reduction in colorectal cancer incidence and mortality:

  • lowering the screening start age to 40 or 45 years would result in additional reductions of 2-6 percentage points in colorectal cancer incidence and 2–9 percentage points in colorectal cancer mortality in all scenarios
  • extending the age of ceasing screening to 79 years or 84 years would result in an additional reduction of 1–2 percentage points in colorectal cancer incidence and 2–5 percentage points in colorectal cancer mortality in all scenarios
  • extending the screening age from the current 50–74 years to 40–84 years would result an additional overall reduction of 7–8 percentage points in cancer incidence and 12–14 percentage points in cancer mortality in all scenarios.

If the screening age range was widened from the current 50–74 years to 40–84 years, an overall reduction of 7–8 percentage points in cancer incidence and 12–14 percentage points in cancer mortality was estimated.

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Cost-effectiveness

With an indicative willingness-to-pay threshold of A$50,000 per life–year saved in Australia, only two strategies were found to be cost-effective in all scenarios after calculating the incremental cost-effective ratio (ICER):

  • the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. (ICER A$4,264–8,075 per life–year saved, depending on participation)
  • screening at 45–74 years (ICER A$19,451–40,813 per life–year saved, depending on participation).

Extending screening to older ages was not cost-effective in any participation scenario.

Starting screening at age 40 years was not found to be cost-effective in all participation scenarios, but starting at 45 years was found to be potentially cost-effective in all participation scenarios.

The cost-effectiveness modelling is described in detail in the Technical report.

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Resource utilisation

Predicted resource requirements in the lifetime of 100,000 persons alive at 40 years within the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. strategy (iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. screening every 2 years in people aged 50–74 years) were:

  • 1 million iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. tests and 127,300 colonoscopies in Scenario 1 (perfect screening adherence)
  • 720,200 iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. tests and 66,700 colonoscopies in Scenario 2 (high screening adherence)
  • 472,000 iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. tests and 44,700 colonoscopies in Scenario 3 (low screening adherence).

Extending the screening age-range resulted in predicted increases in resource utilisation, compared with the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. strategy:

  • ScreeningPerforming tests to identify disease in people before any symptoms appear. at 50–79 years would result in a 21–30% increase in colonoscopies in all scenarios.
  • ScreeningPerforming tests to identify disease in people before any symptoms appear. at 50–84 years would result in a 42–64% increase in colonoscopies in all scenarios.
  • ScreeningPerforming tests to identify disease in people before any symptoms appear. at 45–74 years would result in a 7–14% increase in colonoscopies in all scenarios.
  • ScreeningPerforming tests to identify disease in people before any symptoms appear. at 40–74 years would result in a 27-38% increase in colonoscopies in all scenarios.
  • ScreeningPerforming tests to identify disease in people before any symptoms appear. at 40–84 years would result in a 66–91% increase in iFOBTA test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin. tests and a 72–109% increase in colonoscopies in all scenarios.

This modelling is described in detail in the Technical report.

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Balance of benefits to harms

For the current NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease., the model predicted the following NNCs compared with no screening:

  • (Scenario 1) 28 colonoscopies per case prevented and 56 colonoscopies per death prevented
  • (Scenarios 2 and 3) 22 colonoscopies per case prevented and 39–41 colonoscopies per death prevented.

For details, see the Modelling report.

The ‘benefit–harms frontier’ (showing strategies with the favourable balance between benefit and harm, compared with strategies of similar effectiveness considered in the evaluation) and the incremental benefits to harms ratio (IBHR) of the ‘dominating’ strategies are shown in the modelling report. We thus estimated the number of additional colonoscopies required to prevent one additional colorectal cancer case/colorectal death for each strategy, compared with the next most effective strategy on the frontier. These NNCs for the additional deaths prevented for age-extensions of the NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease. are up to 2–14 times higher than that the baseline NNC for the existing NBCSPThe National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease..

For example, at current levels of participation, starting screening from age 45 years would be associated with an additional 67 colonoscopies for each additional death prevented, compared with an NNC of 39 colonoscopies per death prevented by the existing program.

For more information about the balance of benefits to harms, see the Modelling report.

See the Evidence summary and recommendations section for guidance resulting from this modelling.

Next section: evidence summary, recommendations and considerations

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References

  1. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993 May 13;328(19):1365-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8474513.
  2. Hardcastle JD, Chamberlain JO, Robinson MH, Moss SM, Amar SS, Balfour TW, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996 Nov 30;348(9040):1472-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8942775.
  3. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996 Nov 30;348(9040):1467-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8942774.
  4. Segnan N, Armaroli P, Bonelli L, Risio M, Sciallero S, Zappa M, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE. J Natl Cancer Inst 2011 Sep 7;103(17):1310-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21852264.
  5. Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012 Jun 21;366(25):2345-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22612596.
  6. Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010 May 8;375(9726):1624-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20430429.
  7. Zheng S, Chen K, Liu X, Ma X, Yu H, Chen K, et al. Cluster randomization trial of sequence mass screening for colorectal cancer. Dis ColonThe main part of the large bowel, which absorbs water and electrolytes from undigested food (solid waste). Its four parts are the ascending colon, transverse colon, descending colon and sigmoid colon. RectumThe final section of the large bowel, ending at the anus. 2003 Jan;46(1):51-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12544522.
  8. Hoff G, Grotmol T, Skovlund E, Bretthauer M, Norwegian ColorectalReferring to the large bowel, comprising the colon and rectum. Cancer Prevention Study Group. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ 2009 May 29;338:b1846 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19483252.
  9. Cenin DR, St John DJ, Ledger MJ, Slevin T, Lansdorp-Vogelaar I. Optimising the expansion of the National Bowel Cancer Screening Program. The Medical Journal of Australia 2014;201:456-61 Abstract available at https://www.mja.com.au/journal/2014/201/8/optimising-expansion-national-bowel-cancer-screening-program.
  10. Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016;315:2595-609.
  11. Meester RG, Doubeni CA, Lansdorp-Vogelaar I, Jensen CD, van der Meulen MP, Levin TR, et al. Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model. JAMA 2015 Jun 16;313(23):2349-58 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26080339.
  12. van Hees F, Zauber AG, van Veldhuizen H, Heijnen ML, Penning C, de Koning HJ, et al. The value of models in informing resource allocation in colorectal cancer screening: the case of The Netherlands. Gut 2015 Dec;64(12):1985-97 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26063755.
  13. Greuter MJ, Demirel E, Lew JB, Berkhof J, Xu XM, Canfell K, et al. Long-Term Impact of the Dutch Colorectal Cancer Screening Program on Cancer Incidence and Mortality-Model-Based Exploration of the Serrated Pathway. Cancer Epidemiol Biomarkers Prev 2016 Jan;25(1):135-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26598535.
  14. Australian Institute of Health and Welfare. National Bowel Cancer Screening Program: monitoring report 2016. Cancer series no. 98. Cat. no. CAN 97. Canberra: AIHW; 2016.
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Appendices


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