Modelled evaluation of alternative screening technologies
Background[edit source]
The literature review found high-level evidence supporting effectiveness (mortality reduction) of immunochemical faecal occult blood testing (iFOBT) and flexible sigmoidoscopy in population screening for colorectal cancer, compared with no screening. However, there was no high-level evidence evaluating colonoscopy, computed tomography (CT) colonography, or cancer-specific faecal or blood biomarkers.
Future large-scale trials to further evaluate screening strategies are unlikely, due to the cost and necessary duration. When RCT 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.[1][2][3][4][5]
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Modelling study findings[edit source]
In persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, what is the most cost-effective, feasible and acceptable screening modality (iFOBT, flexible sigmoidoscopy, colonoscopy, CT colonography, faecal or blood biomarkers test, or any combinations) compared with no screening? (PSC1c)
A comprehensive validated model of colorectal cancer development and bowel screening (‘Policy1-Bowel’) was used to simulate the National Bowel Cancer Screening Program (NBCSP) and alternative screening approaches (Table 3.3). Details of the methods and result can be found in the Technical Report.
The term ‘adherence’ applies to compliance with recommendations for screening, follow-up and surveillance.
The strategies were evaluated in context of three scenarios:
- Scenario 1 assumes perfect adherence to screening, follow-up and surveillance recommendations.
- Scenario 2 assumes high (but imperfect) participation (participation after first invitation was 57% for screening strategies using iFOBT and faecal/ blood biomarkers test, and was 35% for screening strategies using colonoscopy, sigmoidoscopy and CT colonography).
- Scenario 3 assumes lower participation (participation after first invitation was 27% for screening strategies using iFOBT and faecal/ blood biomarkers test, and was 15% for screening strategies using colonoscopy, sigmoidoscopy and CT colonography).
Specific participation assumptions differed according to screening modality and an individual's screening history and were derived based on currently observed screening participation in Australia and expert opinion for new modalities (see Appendix for details of participation assumptions for each modality).
Table 3.3 Screening strategies evaluated[edit source]
| Strategy name | Description |
|---|---|
| No screening (comparator) | No screening |
| iFOBT2y | iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) |
| iFOBT1y | iFOBT screening every year at age 50–74 years |
| plasmaDNA2y (exploratory modelling based on limited data from a small number of cross-sectional studies; no data on longitudinal outcomes for this technology available) | pDNA screening every 2 years at 50–74 years (pDNA assuming test for methylated SEPT9 DNA, as reported in Church et al 2014).[6] |
| fDNA2y (exploratory modelling based on limited data from a small number of cross-sectional studies; no data on longitudinal outcomes for this technology available) | fDNA screening every 2 years at age 50–74 years (multi-target faecal testing including iFOBT, assuming test characteristics reported in Imperiale et al (2014).[7] |
| fDNA5y (exploratory modelling based on limited data from a small number of cross-sectional studies; no data on longitudinal outcomes for this technology available) | fDNA screening every 5 years at age 50–74 years |
| COL10y | COL screening every 10 years at ages 55, 65 and 75 years |
| SIG10y | SIG screening every 10 years at ages 55, 65 and 75 years |
| CTC10y (exploratory modelling based on limited data from a small number of cross-sectional studies; no data on longitudinal outcomes for this technology available) | CTC screening every 10 years at ages 55, 65 and 75 years |
| SIG@60 | Once-off SIG screening at age 60 years |
| SIG@55_iFOBT2y @60To74 | Once-off SIG screening at age 55 years combined with iFOBT every 2 years at age 60–74 years |
| COL@50_iFOBT2y @52To74 | Once-off COL screening at age 50 years combined with iFOBT every 2 years at age 52–74 years^ |
| iFOBT2y+SIG@50 | iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) combined with SIG at age 50 years for negative iFOBT |
| iFOBT2y+SIG@54_64_74 | iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) combined with SIG at ages 54, 64 and 74 years for negative iFOBT |
| iFOBT2y+plasmaDNA | iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) combined with pDNA testing in under-screened individuals^^ |
COL: colonoscopy; CTC: computed tomographic colonography; iFOBT: immunochemical faecal occult blood test; fDNA: faecal DNA test; pDNA: plasma DNA test; SIG: flexible sigmoidoscopy
Notes:
^: Individuals aged 50 years who do not participate in colonoscopy screening will be invited to have an iFOBT.
^^: Under-screened individuals are those who are not under colonoscopy surveillance and have not had an iFOBT test in the past 4 years (including those who are eligible for screening but have never have a screening test).
No leakage (drop in participation) from main program is assumed after pDNA is offered (a favourable scenario).
Health outcomes (benefits)[edit source]
Perfect adherence[edit source]
When assuming perfect adherence to screening, follow-up and surveillance recommendations (Scenario 1), colorectal cancer screening was predicted to reduce age-standardised risk (in 0-89 years) of colorectal cancer incidence by 23–67% and colorectal cancer mortality by 30–82% (encompassing a range of results, depending on screening technology and screening interval and age range), compared to no screening.
For seven screening strategies, a reduction in age-standardised colorectal cancer mortality risk (in 0-89 years) of greater than 75% was predicted in perfectly adherent cohorts. These strategies were:
- faecal DNA test (fDNA) screening every 2 years at age 50–74 years (82% reduction)
- colonoscopy screening every 10 years at age 55, 65 and 75 years (77% reduction)
- once-only colonoscopy screening at age 50 years combined with iFOBT screening every 2 years at age 52–74 years (80% reduction)
- iFOBT screening every year at age 50–74 years (81% reduction)
- iFOBT screening every 2 years at age 50–74 years (75% reduction)
- iFOBT screening every 2 years at age 50–74 years , with adjunctive flexible sigmoidoscopy at age 50 years for individuals with negative iFOBT results (77% reduction)
- iFOBT screening every 2 years at age 50–74 years, with adjunctive flexible sigmoidoscopy screening at age 54, 64 and 74 years for individuals with negative iFOBT (79% reduction).
Imperfect adherence[edit source]
After accounting for realistic adherence to screening, follow-up and surveillance recommendations:
- When assuming high participation (Scenario 2), colorectal cancer screening was predicted to reduce age-standardised risk (in 0-89 years) of colorectal cancer incidence by 6–48% and colorectal cancer mortality by 7–69%, compared to no screening.
- When assuming low participation (Scenario 3), colorectal cancer screening was predicted to reduce age-standardised risk (in 0-89 years) of colorectal cancer incidence by 3–38% and colorectal cancer mortality by 3–56%, compared to no screening.
Seven strategies predicted a greater than 50% mortality reduction in Scenario 2 (high participation) and greater than 35% reduction in Scenario 3 (low participation):
- fDNA screening every 2 years (63% in Scenario 2; 44% in Scenario 3)
- once-off colonoscopy screening at age 50 years combined with 2-yearly iFOBT screening at 52–74 years (57% in Scenario 2; 40% in Scenario 3)
- iFOBT screening every year at age 50–74 years (69% in Scenario 2; 56% in Scenario 3)
- iFOBT screening every 2 years at age 50–74 years (53% in Scenario 2; 36% in Scenario 3)
- iFOBT screening every 2 years at age 50–74 years, with adjunctive flexible sigmoidoscopy screening at age 50 years for individuals with negative iFOBT (53% in Scenario 2; 37% in Scenario 3)
- iFOBT screening every 2 years at age 50–74 years, with adjunctive flexible sigmoidoscopy screening at age 54, 64 and 74 years for individuals with negative iFOBT (55% in Scenario 2; 37% in Scenario 3)
- iFOBT screening every 2 years, with plasma DNA testing (pDNA) for under-screened individuals, assuming that the offer of pDNA does not induce any ‘leakage’ (participation drop) in iFOBT screening – a favourable assumption (54% in Scenario 2; 39% in Scenario 3).
Cost-effectiveness[edit source]
Of the strategies examined, only computed tomography colonography (CTC) screening every 10 years and iFOBT screening every 2 years remained cost-effective in all screening participation scenarios considered, in context of an indicative willingness-to-pay threshold of A$50,000 per life–year saved in Australia. Of these two strategies, iFOBT was the most effective, with an incremental cost-effectiveness ratio of A$6,412–33,535 per life–year saved, compared with CTC screening every 10 years (depending on participation).
Therefore, the current NBCSP is the most effective strategy for colorectal cancer screening in Australia that is also cost-effective.
Resource utilisation[edit source]
Modelling was used to estimate the number of iFOBT test, pDNA tests, fDNA tests, colonoscopy, flexible sigmoidoscopy and CTC tests in the lifetime of 100,000 persons alive at 40 years for each strategy.
In all participation scenarios, colonoscopy screening every 10 years, once-off colonoscopy screening at age 50 years combined with iFOBT screening every 2 years, iFOBT screening every year and fDNA screening every 2 years were predicted to lead to the highest number of colonoscopy procedures. Screening with once-off flexible sigmoidoscopy at 60 years, with sigmoidoscopy every 10 years, or with CTC screening every 10 years, were estimated to lead to the lowest number of colonoscopies.
Balance of benefits to harms[edit source]
In all participation scenarios, strategies assuming pDNA screening every 2 years, colonoscopy screening every 10 years, and once-off colonoscopy screening at age 50 years combined with iFOBT every 2 years, were estimated to be associated with the highest number-needed-to-colonoscope (NNC) per colorectal cancer case or colorectal cancer death prevented, compared with the other strategies (i.e. these strategies had the least favourable ratio of benefits to harms).
When compared with iFOBT screening every 2 years, five strategies were found to be associated with greater reductions in colorectal cancer deaths but also resulted in higher numbers of colonoscopies in all scenarios (details in Table 9.3):
- fDNA screening every 2 years at age 50–74 years (fDNA2y)
- Once-off COL screening at age 50 years, combined with iFOBT every 2 years at age 52–74 years (COL@50_iFOBT2y)
- iFOBT screening every year at age 50–74 (iFOBT1y)
- iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) combined with flexible sigmoidoscopy at age 50 for negative iFOBT (iFOBT2y+SIG@50)
- iFOBT screening every 2 years at age 50–74 years (NBCSP from 2020) combined with SIG at 54, 64 and 74 years for negative iFOBT (iFOBT2y+SIG@54_64_74).
These five strategies were estimated to be associated with a higher NNC per colorectal cancer death prevented compared with iFOBT every 2 years (278–1150 in Scenario 1, 106–381 in Scenario 2, and 65–190 in Scenario 3).
No strategy was predicted to result in both fewer colorectal cancer deaths and fewer colonoscopies than iFOBT every 2 years. This finding implies that the strategy adopted in the current NBCSP has an optimal balance of benefits and harms, given the strategies considered in this evaluation.
See the Evidence summary and recommendations section for guidance resulting from this modelling.
References[edit source]
- ↑ 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 Available from: https://www.mja.com.au/journal/2014/201/8/optimising-expansion-national-bowel-cancer-screening-program.
- ↑ 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.
- ↑ 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26080339.
- ↑ 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26063755.
- ↑ 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26598535.
- ↑ Church TR, Wandell M, Lofton-Day C, Mongin SJ, Burger M, Payne SR, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014 Feb;63(2):317-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23408352.
- ↑ Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014 Apr 3;370(14):1287-97 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24645800.
Appendices[edit source]
