Australia Postgraduate Award PhD Scholarship, Translational Cancer Research Network Top-up scholarship (supported by Cancer Institute NSW) and Cancer Council NSW.

Objective To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk. Design Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon). Setting A parallel guideline committee ( BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures. Population Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%). Comparisons Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence. Main outcome measures Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach. Results Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates. Conclusions Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.

Background: There is growing evidence for personalising colorectal cancer (CRC) screening based on risk factors. We compared the cost-effectiveness of personalised CRC screening based on polygenic risk and family history to uniform screening.Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalised screening. Individuals were categorised based on polygenic risk and family history of CRC. We varied screening strategies by start age, interval and test and estimated costs and quality-adjusted life years (QALYs). In our analysis we: 1) assessed the costeffectiveness of uniform screening; 2) developed personalised screening scenarios based on optimal screening strategies by risk group; 3) compared the cost-effectiveness of both.Results: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual faecal immunochemical testing (FIT) from 50-74 years, whereas for personalised screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50. Although these scenarios gained the same number of QALYs (17,887), personalised screening was not cost effective, costing an additional $428,953 due to costs associated with determining risk

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Objective(s) To estimate the impact of various expansion scenarios of the National Bowel Cancer Screening program (NBSCP) on the number of bowel cancer deaths prevented. Impact of the expansion scenarios on colonoscopy demand was also investigated. Design MISCAN-Colon, a well-established, validated computer simulation model for bowel cancer screening, was adjusted to reflect the Australian situation. In July 2013, we simulated the effects of screening over a 50 year period, starting in 2006. The model parameters included participation rates for screening and follow up, cancerous and pre-cancerous lesion identification rates, bowel cancer incidence, mortality and the outcomes of the NBCSP. Five implementation scenarios, based on biennial screening using an immunochemical faecal occult blood test, were developed and modelled. A sensitivity analysis that increased screening participation to 60% was also conducted. Setting/ Participants Australian residents aged 50 to 74 years Main outcome measures Impact and comparison of five implementation scenarios on the number of bowel cancer deaths prevented and demand for colonoscopy. Results In its current state, MISCAN-Colon calculated that the NBCSP should prevent 35,169 bowel cancer deaths in the coming 40 years. Accelerating the expansion of the program to achieve biennial screening by 2020, more than 70,000 deaths would be prevented. If complete implementation of biennial screening resulted in a corresponding increase in participation to 60%, the number of deaths prevented increased across all scenarios. Conclusion(s) The findings strongly support the need for rapid implementation of the National Bowel Cancer Screening Program. Compared to the current situation, achieving biennial screening by 2020 could result in 100% more bowel cancer deaths being prevented (approximately 35,000) in the coming 40 years.

Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

The MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.

IntroductionTo reduce the burden of colorectal cancer (CRC) in Shanghai, China, a CRC screening programme was commenced in 2013 inviting those aged 50–74 years to triennial screening with a faecal immunochemical test (FIT) and risk assessment. However, it is unknown whether this is the optimal screening strategy for this population. We aimed to determine the optimal CRC screening programme for Shanghai in terms of benefits, burden, harms and cost-effectiveness.MethodsUsing Microsimulation Screening Analysis-Colon (MISCAN-Colon), we estimated the costs and effects of the current screening programme compared with a situation without screening. Subsequently, we estimated the benefits (life years gained (LYG)), burden (number of screening events, colonoscopies and false-positive tests), harms (number of colonoscopy complications) and costs (Renminb (¥)) of screening for 324 alternative screening strategies. We compared several different age ranges, screening modalities, intervals and FIT cut-off levels. An incremental cost-effectiveness analysis determined the optimal strategy assuming a willingness-to-pay of ¥193 931 per LYG.ResultsCompared with no screening, the current screening programme reduced CRC incidence by 40% (19 cases per 1000 screened individuals) and CRC mortality by 67% (7 deaths). This strategy gained 32 additional life years, increased colonoscopy demand to 1434 per 1000 individuals and cost an additional ¥199 652. The optimal screening strategy was annual testing using a validated one-sample FIT, with a cut-off of 10 µg haemoglobin per gram from ages 45 to 80 years (incremental cost-effectiveness ratio, ¥62 107). This strategy increased LY by 0.18% and costs by 27%. Several alternative cost-effective strategies using a validated FIT offered comparable benefits to the current programme but lower burden and costs.ConclusionsAlthough the current screening programme in Shanghai is effective at reducing CRC incidence and mortality, the programme could be optimised using a validated FIT. When implementing CRC screening, jurisdictions with limited health resources should use a validated test.