Screening and early detection is one of the most effective approaches to reduce the population-level impact of cancer. Novel approaches to screening such as multi-cancer early detection tests (MCEDs) may further reduce cancer incidence and mortality. Many MCEDs detect fragments of circulating DNA containing mutations that originated from tumour cells, thereby informing both the presence of cancer and the cell-type of origin. In this review, we examine the current evidence of MCEDs as a potential tool to improve population-based cancer outcomes. We review the role of MCEDs to address low participation rates, disparities among underserved populations, changing epidemiology of common cancers, and the absence of screening tests for many cancer types. MCEDs have the potential to increase participation in cancer screening programs, as they may be less invasive than other procedures, and can screen for multiple cancer types in one appointment. Additionally, due to the lack of specialized collection equipment needed for these tests, underscreened populations and targeted populations could gain greater access to screening. Finally, because MCEDs can detect cancer types without screening tests that are moderately common and increasing in western populations, efficacious tests for these sites could alleviate the cancer burden and improve patient outcomes. While these tests offer great promise, considerable limitations and evidence gaps must be addressed. Notable limitations include scenarios where early detection does not improve survival outcomes, the costs and impact on health care resources for false positives, and false reassurance with subsequent lack of adherence to existing screening protocols.

The association between red meat consumption and colorectal cancer has been rigorously examined. However, a more comprehensive understanding of how the intake of unprocessed red meat contributes to the development of early precancerous colorectal lesions, such as advanced colorectal adenomas (ACRAs), requires further investigation. We examined the associations between different types of red meat intake and ACRAs in a sample population of 1083 individuals aged ≥ 50 years undergoing an initial screening colonoscopy in Calgary, Alberta, Canada. Associations between grams per day of total, processed, and unprocessed red meat from diet history questionnaires and ACRAs were evaluated with multivariable logistic regression models. We also applied cubic spline models fitted with three knots (10th, 50th, and 90th percentiles) to identify potential nonlinear associations. We did not observe a meaningful association between unprocessed red meat intake and the presence of ACRAs. In contrast, for every 10 g/d increase in total and processed meat intake, we observed an increase in the odds of ACRAs at the screening colonoscopy (adjusted odds ratio (OR) = 1.05, 95% [CI = 1.01–1.09], p = 0.04) and (adjusted OR = 1.11, 95% [CI = 1.02–1.20], p = 0.02), respectively. This study highlights the importance of differentiating between types of red meat consumption in the context of dietary risks associated with ACRAs.

Background: The increasing rates of early-onset colorectal cancer in Canada suggest that earlier screening may be warranted. Canadian guidelines recommend biennial screening at 50 years of age with a fecal immunochemical test (FIT). Methods: OncoSim was used to project the outcomes of revised colorectal cancer screening guidelines in Canada for four cohorts born between 1973 and 1992. Cohort risk ratios were calibrated to Canadian incidence data to reflect early-onset trends. We evaluated the incremental colonoscopy burden of earlier FIT screening and primary colonoscopy screening compared with a reference scenario screening with FIT biennially at 50 years of age (FIT 50). Sensitivity analyses were performed by adjusting screening participation and discount rates. Results: FIT at 45 and 40 years of age (FIT 45 and FIT 40, respectively) increased the colonoscopy demand by 3.9% and 6.6%, respectively, over the lifetime of screening. Colonoscopy screening resulted in 89.0% to 116.7% more colonoscopies than FIT 50. Screening and total costs increased in all scenarios, but treatment costs decreased. FIT 45 and FIT 40 reduced the incidence by 103 and 161 and colorectal cancer deaths by 43 and 71 per 100,000, respectively. Colonoscopy screening led to 858 to 954 fewer cases and 260 to 303 fewer deaths per 100,000, resp. FIT 45and FIT 40 had incremental cost-effectiveness ratios of $5,850 per quality-adjusted life year (QALY) and $7,038 per QALY, respectively, compared with FIT 50. Colonoscopy scenarios had incremental cost-effectiveness ratios of $2,743 to $7,509 per QALY. Conclusions: Updated screening can reduce the colorectal cancer burden in younger populations. Increasing FIT screening with earlier initiation is more feasible logistically than increasing colonoscopy first approaches. Impact: These findings may inform future guideline revisions in Canada addressing early-onset colorectal cancer.

Objective: To quantify the resource use of revising breast cancer screening guidelines to include average-risk women aged 40–49 years across Canada from 2024 to 2043 using a validated microsimulation model. Setting: OncoSim-Breast microsimulation platform was used to simulate the entire Canadian population in 2015–2051. Methods: We compared resource use between current screening guidelines (biennial screening ages 50–74) and alternate screening scenarios, which included annual and biennial screening for ages 40–49 and ages 45–49, followed by biennial screening ages 50–74. We estimated absolute and relative differences in number of screens, abnormal screening recalls without cancer, total and negative biopsies, screen-detected cancers, stage of diagnosis, and breast cancer deaths averted. Results: Compared with current guidelines in Canada, the most intensive screening scenario (annual screening ages 40–49) would result in 13.3% increases in the number of screens and abnormal screening recalls without cancer whereas the least intensive scenario (biennial screening ages 45–49) would result in a 3.4% increase in number of screens and 3.8% increase in number of abnormal screening recalls without cancer. More intensive screening would be associated with fewer stage II, III, and IV diagnoses, and more breast cancer deaths averted. Conclusions: Revising breast cancer screening in Canada to include average-risk women aged 40–49 would detect cancers earlier leading to fewer breast cancer deaths. To realize this potential clinical benefit, a considerable increase in screening resources would be required in terms of number of screens and screen follow-ups. Further economic analyses are required to fully understand cost and budget implications.

Introduction: The United States of America reignited their Cancer Moonshot Initiative in 2022 with an ambitious goal to reduce cancer mortality by 50% over the next 25 years. In this study, we estimated how and whether a similar cancer control initiative could be achieved in Canada. Methods: We used the OncoSim microsimulation suite to address three questions: (1) what is the expected mortality from cancer in Canada by 2050 given the current trends?; (2) what would be the maximal impact on reducing cancer mortality with prevention and increased screening activities? and, (3) if a 50% reduction in projected cancer mortality could not be achieved through the primary and secondary intervention efforts, what additional advancements and discoveries would be needed to fill the “lunar gap”? We modeled the joint impact of risk-factor reduction and screening, as well as the independent effects of prevention and screening alone, on projected cancer mortality. Results: Our models suggest that there will be an expected 133,395 cancer deaths in 2050 in Canada. Approximately 33% of these cancer deaths could be prevented by risk-factor reduction and increased screening programs by the year 2050. This would leave a “lunar gap” of about 16%–17% that would need to be bridged with novel discoveries in cancer risk prevention, early detection, and treatment. Conclusion: While current knowledge and implementation of prevention and screening would have a considerable impact on a Canadian cancer moonshot, additional efforts are needed to implement cancer control initiatives and fuel additional discoveries to fill the gap.

Supplementary Table S6 shows the results of the sensitivity analysis assessing parameter uncertainty of the modelled screening participation rate in the base-case.