COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

Access to colorectal cancer screening in populations in China, 2020: A coverage-focused synthesis analysis.

In populations in China, colorectal cancer (CRC) screening can be mainly accessed through organized screening, opportunistic screening, and physical examination. This screening intervention is found to be effective but the exact coverage rate is difficult to measure. Based on data from published articles, official websites, and available program reports, the screening coverage rate and related indicators were quantified. A rapid review was then conducted to estimate the overall and the breakdown coverage rates of the sub-type screening services, by leveraging the numbers of articles and the by-type median sample sizes. Up to 2020, two central government-funded and four provincial/municipal-level organized CRC screening programs have been initiated and included in this analysis. For populations aged 40-74, the estimated coverage rate of organized programs in China was 2.7% in 2020, and the 2-year cumulative coverage rate in 2019-2020 was 5.3% and the 3-year cumulative coverage rate in 2018-2020 was 7.7%. The corresponding coverage rates of 50-74-year-olds were estimated to be 3.4%, 7.1%, and 10.3%, respectively. Based on the rapid review approach, the overall screening coverage rate for 40-74 years, considering organized screening programs, opportunistic screening, and physical examinations, was then estimated to be 3.0% in China in 2020. However, comparing the findings of this study with the number of health check-ups reported in the local national health statistics yearbooks suggests that the number of CRC physical examinations may be underestimated in this study. The findings suggest that further efforts are needed to improve population access to CRC screening in China. Furthermore, evidence for access to opportunistic CRC screening and physical examination is limited, and more quantitative investigation is needed.

Estimating the economic burden of colorectal cancer in China, 2019-2030: A population-level prevalence-based analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population-level is critical in informing policymaking, but such data are currently limited in China. METHODS: From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature-death-related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence-based approach. The per-person direct expenditure and work loss days were from a multicenter study; the premature-death-related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019. RESULTS: In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to

SMARTERscreen protocol: a three-arm cluster randomised controlled trial of patient SMS messaging in general practice to increase participation in the Australian National Bowel Cancer Screening Program.

BACKGROUND: Australia persistently has one of the highest rates of colorectal cancer (CRC) in the world. Australia's National Bowel Cancer Screening Program (NBCSP) sends a biennial Faecal Immunochemical Test (FIT)-the 'NBCSP kit'-to everyone eligible for the programme between 50 and 74 years old; however, participation in the programme is low, especially in the 50- to 60-year-old age group. Our previous efficacy trial ('SMARTscreen') demonstrated an absolute increase in uptake of 16.5% (95% confidence interval = 2.02-30.9%) for people sent an SMS with motivational and instructional videos, from their general practice prior to receiving their NBCSP kit, compared to those receiving usual care. Building on the strengths of the SMARTscreen trial and addressing limitations, the 'SMARTERscreen' trial will test the effect on participation in the NBCSP of sending either an SMS only or an SMS with online video material to general practice patients due to receive their NBCSP compared to 'usual care'. METHODS: SMARTERscreen is a three-arm stratified cluster randomised controlled trial involving 63 general practices in two states in Australia. Eligible patients are patients who are aged 49-60 years and due to receive their NBCSP kit within the next 2 weeks during the intervention period. General practices will be equally randomised to three trial arms (21:21:21, estimated average 260 patients/practice). The two interventions include (i) an SMS with an encouraging message from their general practice or (ii) the same SMS with weblinks to additional motivational and instructional videos. The control arm will receive 'usual care'. Using the intention-to-treat approach, primary analysis will estimate the three pair-wise between-arm differences in the proportion of eligible patients who participate in the NBCSP within 6 months of when their kit is sent, utilising screening data from the Australian National Cancer Screening Register (NCSR). Patient intervention adherence to the interventions will also be evaluated. Findings will be incorporated into the Policy1-Bowel microsimulation model to estimate the long-term health benefits and cost-effectiveness of the interventions. DISCUSSION: SMARTERscreen will provide high-level evidence determining whether an SMS or an SMS with web-based material sent to general practice patients prior to receiving their NBCSP kit increases participation in bowel cancer screening. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000036617. Registered on 13 January 2023. Trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385119&isClinicalTrial=False.

Potential global loss of life expected due to COVID-19 disruptions to organised colorectal cancer screening.

Background: Screening for colorectal cancer (CRC) decreases cancer burden through removal of precancerous lesions and early detection of cancer. The COVID-19 pandemic has disrupted organised CRC screening programs worldwide, with some programs completely suspending screening and others experiencing significant decreases in participation and diagnostic follow-up. This study estimated the global impact of screening disruptions on CRC outcomes, and potential effects of catch-up screening. Methods: Organised screening programs were identified in 29 countries, and data on participation rates and COVID-related changes to screening in 2020 were extracted where available. Four independent microsimulation models (ASCCA, MISCAN-Colon, OncoSim, and Policy1-Bowel) were used to estimate the long-term impact on CRC cases and deaths, based on decreases to screening participation in 2020. For countries where 2020 participation data were not available, changes to screening were approximated based on excess mortality rates. Catch-up strategies involving additional screening in 2021 were also simulated. Findings: In countries for which direct data were available, organised CRC screening volumes at a country level decreased by an estimated 1.3-40.5% in 2020. Globally, it is estimated that COVID-related screening decreases led to a deficit of 7.4 million fewer faecal screens performed in 2020. In the absence of any organised catch-up screening, this would lead to an estimated 13,000 additional CRC cases and 7,900 deaths globally from 2020 to 2050; 79% of the additional cases and 85% of additional deaths could have been prevented with catch-up screening, respectively. Interpretation: COVID-19-related disruptions to screening will cause excess CRC cases and deaths, but appropriately implemented catch-up screening could have reduced the burden by over 80%. Careful management of any disruption is key to improving the resilience of colorectal cancer screening programs. Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.

A modelled evaluation of the impact of COVID-19 on breast, bowel, and cervical cancer screening programmes in Australia.

Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services, the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel, and cervical cancer screening programmes on cancer outcomes and cancer services. We used the Policy1 modelling platforms to predict outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9, and 12 mo. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts. We found that a 12-mo screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020-2021) and colorectal cancer (up to 12.1% reduction over 2020-21), and increase cervical cancer diagnoses (up to 3.6% over 2020-2022), with upstaging expected for these cancer types (2, 1.4, and 6.8% for breast, cervical, and colorectal cancers, respectively). Findings for 6-12-mo disruption scenarios illustrate that maintaining screening participation is critical to preventing an increase in the burden of cancer at a population level. We provide programme-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programmes and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.

The 'hot zone policy' for colorectal cancer screening presents unique risks and opportunities for rural Australia.

OBJECTIVE: Colorectal cancer has geographic inequities in Australia, with higher mortality rates and lower participation in the National Bowel Cancer Screening Program (NBCSP) in remote and rural areas. The at-home kit is temperature-sensitive, necessitating a 'hot zone policy' (HZP); kits are not sent when an area's average monthly temperature is above 30°C. Australians in HZP areas are susceptible to potential screening disruptions but may benefit from well-timed interventions to improve participation. This study describes the demographics of HZP areas and estimates the impacts of potential screening changes. METHODS: The number of individuals in HZP areas was estimated, as well as correlations with remoteness, socio-economic and Indigenous status. The potential impacts of screening changes were estimated. RESULTS: Over a million eligible Australians live in HZP areas, which are more likely to be remote/rural, have lower socio-economic status and higher Indigenous populations. Predictive modelling estimates that any 3-month screening disruption would increase CRC mortality rates up to 4.1 times more in HZP areas vs unaffected areas, while targeted intervention could decrease mortality rates 3.4 times more in HZP areas. CONCLUSION: People living in affected areas would be negatively impacted by any NBCSP disruption, compounding existing inequities. However, well-timed health promotion could have a stronger impact.

Colon and rectal cancer treatment patterns and their associations with clinical, sociodemographic and lifestyle characteristics: analysis of the Australian 45 and Up Study cohort.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer globally and the second leading cause of cancer death. We examined colon and rectal cancer treatment patterns in Australia. METHODS: From cancer registry records, we identified 1,236 and 542 people with incident colon and rectal cancer, respectively, diagnosed during 2006-2013 in the 45 and Up Study cohort (267,357 participants). Cancer treatment and deaths were determined via linkage to routinely collected data, including hospital and medical services records. For colon cancer, we examined treatment categories of "surgery only", "surgery plus chemotherapy", "other treatment" (i.e. other combinations of surgery/chemotherapy/radiotherapy), "no record of cancer-related treatment, died"; and, for rectal cancer, "surgery only", "surgery plus chemotherapy and/or radiotherapy", "other treatment", and "no record of cancer-related treatment, died". We analysed survival, time to first treatment, and characteristics associated with treatment receipt using competing risks regression. RESULTS: 86.4% and 86.5% of people with colon and rectal cancer, respectively, had a record of receiving any treatment ≤2 years post-diagnosis. Of those treated, 93.2% and 90.8% started treatment ≤2 months post-diagnosis, respectively. Characteristics significantly associated with treatment receipt were similar for colon and rectal cancer, with strongest associations for spread of disease and age at diagnosis (p<0.003). For colon cancer, the rate of "no record of cancer-related treatment, died" was higher for people with distant spread of disease (versus localised, subdistribution hazard ratio (SHR)=13.6, 95% confidence interval (CI):5.5-33.9), age ≥75 years (versus age 45-74, SHR=3.6, 95%CI:1.8-7.1), and visiting an emergency department ≤1 month pre-diagnosis (SHR=2.9, 95%CI:1.6-5.2). For rectal cancer, the rate of "surgery plus chemotherapy and/or radiotherapy" was higher for people with regional spread of disease (versus localised, SHR=5.2, 95%CI:3.6-7.7) and lower for people with poorer physical functioning (SHR=0.5, 95%CI:0.3-0.8) or no private health insurance (SHR=0.7, 95%CI:0.5-0.9). CONCLUSION: Before the COVID-19 pandemic, most people with colon or rectal cancer received treatment ≤2 months post-diagnosis, however, treatment patterns varied by spread of disease and age. This work can be used to inform future healthcare requirements, to estimate the impact of cancer control interventions to improve prevention and early diagnosis, and serve as a benchmark to assess treatment delays/disruptions during the pandemic. Future work should examine associations with clinical factors (e.g. performance status at diagnosis) and interdependencies between characteristics such as age, comorbidities, and emergency department visits.

Colonoscopies in Australia - how much does the National Bowel Cancer Screening Program contribute to colonoscopy use?

Objectives and importance of study: Colorectal cancer (CRC) is Australia's fourth most commonly diagnosed cancer. CRC screening is an effective intervention to reduce this burden. The National Bowel Cancer Screening Program (NBCSP) provides 2-yearly immunochemical faecal occult blood tests (iFOBTs) to Australians aged 50-74 years; a diagnostic colonoscopy is conducted after a positive iFOBT. Clinical guidelines inform colonoscopy usage, and appropriate use of these guidelines is vital to investigate gastrointestinal symptoms, detect bowel abnormalities and CRC, and remove precancerous polyps. Colonoscopy services are under strain, with limited formal strategies to prioritise patients. There are concerns among practitioners and patient advocates that the NBCSP generates additional colonoscopy requests and increases wait times, worsening patient outcomes and prolonging distress. In this research study, we estimate and project colonoscopy use in Australia from 2001 to 2030 and determine the impact of the NBCSP by examining model-estimated NBCSP colonoscopy demand. METHODS: Colonoscopy use in Australia was compiled using Medicare Benefits Schedule (MBS) claims for colonoscopies from 2001 to 2019. From these data, projections were made from 2020 to 2030. Policy1-Bowel, a microsimulation model, was used to estimate NBCSP-related colonoscopy demand from screening follow-up and colonoscopic surveillance from 2006 to 2030. RESULTS: MBS-funded colonoscopy use increased from 284 676 in 2001 to 663 213 in 2019. Annual use is projected to be more than 780 000 by 2030. Of these, 10-14% are projected to be generated by the NBCSP. Per-capita MBS-funded colonoscopy utilisation increased 0.2% annually over 2015-2019, a slowing of growth compared to previous trends. CONCLUSION: The NBCSP accounts for a modest fraction of colonoscopy use in Australia, and a better understanding of colonoscopy use not associated with the NBCSP is needed. Promoting adherence to guideline-recommended iFOBT and colonoscopy use could ease pressure on services and improve outcomes.

The potential for tailored screening to reduce bowel cancer mortality for Aboriginal and Torres Strait Islander peoples in Australia: Modelling study.

BACKGROUND: Australian Aboriginal and Torres Strait Islander peoples experience health and socioeconomic disparities, including lower life-expectancy, have a younger mean age of colorectal cancer (CRC) diagnosis, and lower CRC survival than non-Indigenous Australians. The National Bowel Cancer Screening Program (NBCSP) provides biennial CRC screening for Australians aged 50-74 years to reduce the burden of CRC. The 2019 participation rate was 42% nationwide and 23% in Aboriginal and Torres Strait Islander peoples. For Aboriginal and Torres Strait Islander peoples, this study aims to estimate the health outcomes and cost-effectiveness of the current NBCSP and extensions to include people < 50 years. METHODS: An existing microsimulation model, Policy1-Bowel, was adapted to the Aboriginal and Torres Strait Islander population and was used to evaluate three strategies assuming biennial iFOBT screening from 50-74, 45-74, or 40-74 years under two participation scenarios: 23% and 42% per screening round (psr.). RESULTS: At 23-42% participation psr., the current NBCSP was predicted to reduce lifetime CRC incidence and mortality by 14-24% and 23-39%, respectively, be cost-effective (incremental cost-effectiveness ratio <$13,000/life-year saved), and be associated with a benefits-and-burden balance of 51-53 number-needed-to-colonoscope (NNC) per CRC death prevented of . Lowering the screening start age to 40(45) would further reduce CRC incidence and CRC mortality by 7-11(4-5) percentage points, be cost-effective, and be associated with an incremental NNC- of > 95 (> 60). CONCLUSION: For Aboriginal and Torres Strait Islander peoples, the current NBCSP is cost-effective but participation is limited. Lowering the screening start age will further reduce CRC incidence and mortality. POLICY SUMMARY: These findings highlight a need to increase NBCSP participation whilst exploring the feasibility and acceptability of lowering the NBCSP start age for Aboriginal and Torres Strait Islander peoples. These findings could inform new co-designed, community-led strategies to improve CRC outcomes for Aboriginal and Torres Strait Islander peoples.

Trends in colon and rectal cancer mortality in Australia from 1972 to 2015 and associated projections to 2040.

Previously published sub-site Australian projections for colon and rectal cancers to 2035 using the World Health Organization's mortality database sourced from the Australian Bureau of Statistics (ABS) predicted mortality rate decreases for colon cancer and increases for rectal cancer. There are complexities related to the interpretation of ABS's Australian colon and rectal cancer mortality rates, which could lead to possible inaccuracies in mortality rates for these sub-sites. The largest Australian population-wide registry, New South Wales Cancer Registry (NSWCR), compares routinely-reported causes of death with the recorded medical history from multiple data sources. Therefore, this study used the NSWCR data to project mortality rates for colon and rectal cancers separately to 2040 in Australia. The mortality rates for colon cancer are projected to continuously decline over the period 2015-2040, from 7.0 to 4.7 per 100,000 males, and from 5.3 to 3.2 per 100,000 females. Similar decreasing trends in mortality rates for rectal cancer were projected over the period 2015-2040, from 4.9 to 3.7 per 100,000 males, and from 2.6 to 2.3 per 100,000 females. These projections provide benchmark estimates for the colorectal cancer burden in Australia against which the effectiveness of cancer control interventions can be measured.

Prioritisation of colonoscopy services in colorectal cancer screening programmes to minimise impact of COVID-19 pandemic on predicted cancer burden: A comparative modelling study.

OBJECTIVES: Colorectal cancer (CRC) screening with a faecal immunochemical test (FIT) has been disrupted in many countries during the COVID-19 pandemic. Performing catch-up of missed screens while maintaining regular screening services requires additional colonoscopy capacity that may not be available. This study aimed to compare strategies that clear the screening backlog using limited colonoscopy resources. METHODS: A range of strategies were simulated using four country-specific CRC natural-history models: Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) and MIcrosimulation SCreening ANalysis for CRC (MISCAN-Colon) (both in the Netherlands), Policy1-Bowel (Australia) and OncoSim (Canada). Strategies assumed a 3-month screening disruption with varying recovery period lengths (6, 12, and 24 months) and varying FIT thresholds for diagnostic colonoscopy. Increasing the FIT threshold reduces the number of referrals to diagnostic colonoscopy. Outcomes for each strategy were colonoscopy demand and excess CRC-related deaths due to the disruption. RESULTS: Performing catch-up using the regular FIT threshold in 6, 12 and 24 months could prevent most excess CRC-related deaths, but required 50%, 25% and 12.5% additional colonoscopy demand, respectively. Without exceeding usual colonoscopy demand, up to 60% of excess CRC-related deaths can be prevented by increasing the FIT threshold for 12 or 24 months. Large increases in FIT threshold could lead to additional deaths rather than preventing them. CONCLUSIONS: Clearing the screening backlog in 24 months could avert most excess CRC-related deaths due to a 3-month disruption but would require a small increase in colonoscopy demand. Increasing the FIT threshold slightly over 24 months could ease the pressure on colonoscopy resources.

Health system costs and days in hospital for colorectal cancer patients in New South Wales, Australia.

INTRODUCTION: Colorectal cancer (CRC) care costs the Australian healthcare system more than any other cancer. We estimated costs and days in hospital for CRC cases, stratified by site (colon/rectal cancer) and disease stage, to inform detailed analyses of CRC-related healthcare. METHODS: Incident CRC patients were identified using the Australian 45 and Up Study cohort linked with cancer registry records. We analysed linked hospital admission records, emergency department records, and reimbursement records for government-subsidised medical services and prescription medicines. Cases' health system costs (2020 Australian dollars) and hospital days were compared with those for cancer-free controls (matched by age, sex, geography, smoking) to estimate excess resources by phase of care, analysed by sociodemographic, health, and disease characteristics. RESULTS: 1200 colon and 546 rectal cancer cases were diagnosed 2006-2013, and followed up to June 2016. Eighty-nine percent of cases had surgery, chemotherapy or radiotherapy, and excess costs were predominantly for hospitalisations. Initial phase (12 months post-diagnosis) mean excess health system costs were $50,434 for colon and $60,877 for rectal cancer cases, with means of 16 and 18.5 excess hospital days, respectively. The annual continuing mean excess costs were $6,779 (colon) and $8,336 (rectal), with a mean of 2 excess hospital days each. Resources utilised (costs and days) in these phases increased with more advanced disease, comorbidities, and younger age. Mean excess costs in the year before death were $74,952 (colon) and $67,733 (rectal), with means of 34 and 30 excess hospital days, respectively-resources utilised were similar across all characteristics, apart from lower costs for cases aged ≥75 at diagnosis. CONCLUSIONS: Health system costs and hospital utilisation for CRC care are greater for people with more advanced disease. These findings provide a benchmark, and will help inform future cost-effectiveness analyses of potential approaches to CRC screening and treatment.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Impact of the COVID-19 pandemic on faecal immunochemical test-based colorectal cancer screening programmes in Australia, Canada, and the Netherlands: a comparative modelling study.

BACKGROUND: Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling. METHODS: In this modelling study, we used four country-specific colorectal cancer microsimulation models-Policy1-Bowel (Australia), OncoSim (Canada), and ASCCA and MISCAN-Colon (the Netherlands)-to estimate the potential impact of COVID-19-related disruptions to screening on colorectal cancer incidence and mortality in Australia, Canada, and the Netherlands annually for the period 2020-24 and cumulatively for the period 2020-50. Modelled scenarios varied by duration of disruption (3, 6, and 12 months), decreases in screening participation after the period of disruption (0%, 25%, or 50% reduction), and catch-up screening strategies (within 6 months after the disruption period or all screening delayed by 6 months). FINDINGS: Without catch-up screening, our analysis predicted that colorectal cancer deaths among individuals aged 50 years and older, a 3-month disruption would result in 414-902 additional new colorectal cancer diagnoses (relative increase 0·1-0·2%) and 324-440 additional deaths (relative increase 0·2-0·3%) in the Netherlands, 1672 additional diagnoses (relative increase 0·3%) and 979 additional deaths (relative increase 0·5%) in Australia, and 1671 additional diagnoses (relative increase 0·2%) and 799 additional deaths (relative increase 0·3%) in Canada between 2020 and 2050, compared with undisrupted screening. A 6-month disruption would result in 803-1803 additional diagnoses (relative increase 0·2-0·4%) and 678-881 additional deaths (relative increase 0·4-0·6%) in the Netherlands, 3552 additional diagnoses (relative increase 0·6%) and 1961 additional deaths (relative increase 1·0%) in Australia, and 2844 additional diagnoses (relative increase 0·3%) and 1319 additional deaths (relative increase 0·4%) in Canada between 2020 and 2050, compared with undisrupted screening. A 12-month disruption would result in 1619-3615 additional diagnoses (relative increase 0·4-0·9%) and 1360-1762 additional deaths (relative increase 0·8-1·2%) in the Netherlands, 7140 additional diagnoses (relative increase 1·2%) and 3968 additional deaths (relative increase 2·0%) in Australia, and 5212 additional diagnoses (relative increase 0·6%) and 2366 additional deaths (relative increase 0·8%) in Canada between 2020 and 2050, compared with undisrupted screening. Providing immediate catch-up screening could minimise the impact of the disruption, restricting the relative increase in colorectal cancer incidence and deaths between 2020 and 2050 to less than 0·1% in all countries. A post-disruption decrease in participation could increase colorectal cancer incidence by 0·2-0·9% and deaths by 0·6-1·6% between 2020 and 2050, compared with undisrupted screening. INTERPRETATION: Although the projected effect of short-term disruption to colorectal cancer screening is modest, such disruption will have a marked impact on colorectal cancer incidence and deaths between 2020 and 2050 attributable to missed screening. Thus, it is crucial that, if disrupted, screening programmes ensure participation rates return to previously observed rates and provide catch-up screening wherever possible, since this could mitigate the impact on colorectal cancer deaths. FUNDING: Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.

Health economic evaluation of primary human papillomavirus screening in urban populations in China.

BACKGROUND: On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example. METHODS: We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total. RESULTS: Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold<1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis. CONCLUSION: Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary.

Could HPV Testing on Self-collected Samples Be Routinely Used in an Organized Cervical Screening Program? A Modeled Analysis.

BACKGROUND: Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples. METHODS: Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination ("routinely vaccinated cohorts;" uptake as in Australia) or in the absence of HPV vaccination ("unvaccinated cohorts"). RESULTS: In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it ("additional uptake"). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%-1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%-65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue. CONCLUSIONS: Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake. IMPACT: Consideration could be given to offering self-collection more widely, potentially as an equal choice for women.See related commentary by Lim, p. 245.

Validation of Microsimulation Models against Alternative Model Predictions and Long-Term Colorectal Cancer Incidence and Mortality Outcomes of Randomized Controlled Trials.

Background. This study aimed to assess the validity of 2 microsimulation models of colorectal cancer (CRC), Policy1-Bowel and ASCCA.Methods. The model-estimated CRC risk in population subgroups with different health statuses, "dwell time" (time from incident precancerous polyp to symptomatically detected CRC), and reduction in symptomatically detected CRC incidence after a one-time complete removal of polyps and/or undetected CRC were compared with published findings from 3 well-established models (MISCAN, CRC-SPIN, and SimCRC). Furthermore, 6 randomized controlled trials (RCTs) that provided screening using a guaiac fecal occult blood test (Funen trial, Burgundy trial, and Minnesota Colon Cancer Control Study [MCCCS]) or flexible sigmoidoscopy (NORCCAP, SCORE, and UKFSST) with long-term follow-up were simulated. Model-estimated long-term relative reductions of CRC incidence (RRinc) and mortality (RRmort) were compared with the RCTs' findings. Results. The Policy1-Bowel and ASCCA estimates showed more similarities to CRC-SPIN and SimCRC. For example, overall dwell times estimated by Policy1-Bowel (24.0 years) and ASCCA (25.3) were comparable to CRC-SPIN (25.8) and SimCRC (25.2) but higher than MISCAN (10.6). In addition, ∼86% of Policy1-Bowel's and ∼74% of ASCCA's estimated RRinc and RRmort were consistent with the RCTs' long-term follow-up findings. For example, at 17 to 18 years of follow-up, the MCCCS reported RRmort of 0.67 (95% confidence interval [CI], 0.51-0.83) and 0.79 (95% CI, 0.62-0.97) for the annual and biennial screening arm, respectively, and the UKFSST reported RRmort of 0.70 (95% CI, 0.62-0.79) for CRC at all sites and 0.54 (95% CI, 0.46-0.65) for distal CRC. The corresponding model estimates were 0.65, 0.74, 0.81, and 0.61, respectively, for Policy1-Bowel and 0.65, 0.70, 0.75, and 0.58, respectively, for ASCCA. Conclusion. Policy1-Bowel and ASCCA's estimates are largely consistent with the data included for comparisons, which indicates good model validity.

Pathways to a cancer-free future: a protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia.

INTRODUCTION: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. METHODS AND ANALYSIS: Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged <50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments. ETHICS AND DISSEMINATION: Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.

Improving Australian National Bowel Cancer Screening Program outcomes through increased participation and cost-effective investment.

BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) provides biennial immunochemical faecal occult blood test (iFOBT) screening for people aged 50-74 years. Previous work has quantified the number of colorectal cancer (CRC) deaths prevented by the NBCSP and has shown that it is cost-effective. With a 40% screening participation rate, the NBCSP is currently underutilised and could be improved by increasing program participation, but the maximum appropriate level of spending on effective interventions to increase adherence has not yet been quantified. OBJECTIVES: To estimate (i) reductions in CRC cases and deaths for 2020-2040 attributable to, and (ii) the threshold for cost-effective investment (TCEI) in, effective future interventions to improve participation in the NBCSP. METHODS: A comprehensive microsimulation model, Policy1-Bowel, was used to simulate CRC natural history and screening in Australia, considering currently reported NBCSP adherence rates, i.e. iFOBT participation (∼40%) and diagnostic colonoscopy assessment rates (∼70%). Australian residents aged 40-74 were modelled. We evaluated three scenarios: (1) diagnostic colonoscopy assessment increasing to 90%; (2) iFOBT screening participation increasing to 60% by 2020, 70% by 2030 with diagnostic assessment rates of 90%; and (3) iFOBT screening increasing to 90% by 2020 with diagnostic assessment rates of 90%. In each scenario, we estimated CRC incidence and mortality, colonoscopies, costs, and TCEI given indicative willingness-to-pay thresholds of AUD$10,000-$30,000/LYS. RESULTS: By 2040, age-standardised CRC incidence and mortality rates could be reduced from 46.2 and 13.5 per 100,000 persons, respectively, if current participation rates continued, to (1) 44.0 and 12.7, (2) 36.8 and 8.8, and (3) 31.9 and 6.5. In Scenario 2, 23,000 lives would be saved from 2020-2040 vs current participation rates. The estimated scenario-specific TCEI (Australian dollars or AUD$/year) to invest in interventions to increase participation, given a conservative willingness-to-pay threshold of AUD$10,000/LYS, was (1) AUD$14.9M, (2) AUD$72.0M, and (3) AUD$76.5M. CONCLUSION: Significant investment in evidence-based interventions could be used to improve NBCSP adherence and help realise the program's potential. Such interventions might include mass media campaigns to increase program participation, educational or awareness interventions for practitioners, and/or interventions resulting in improvements in referral pathways. Any set of interventions which achieves at least 70% iFOBT screening participation and a 90% diagnostic assessment rate while costing under AUD$72 million annually would be highly cost-effective (