Projected Reductions in Absolute Cancer–Related Deaths from Diagnosing Cancers Before Metastasis, 2006–2015

Abstract

Background: New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancerrelated deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages. Methods: We obtained stage-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for 17 cancer types for all persons diagnosed ages 50 to 79 years in 18 geographic regions between 2006 and 2015. For a hypothetical cohort of 100,000 persons, we estimated cancer-related deaths under assumptions that cancers diagnosed at stage IV were diagnosed at earlier stages. Results: Stage IV cancers represented 18% of all estimated diagnoses but 48% of all estimated cancer-related deaths within 5 years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15% of all cancer-related deaths. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in allcause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease. Conclusions: Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality. Impact: Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit.

Modeled Reductions in Late-stage Cancer with a Multi-Cancer Early Detection Test

“…10 These potential reductions in mortality represent the cumulative effects of stage shift among multiple cancer types simultaneously with no particular cancer type dominating the effect, and also underscore the problem of contemporary diagnosis of many cancers predominantly at stage IV. 9 Further, the very low false positive rate suggests a PPV of 30% to 40% is achievable under these scenarios, comparing favorably to both the cumulative false positive rate and PPVs for existing single cancer screening tests. 2,[30][31][32] We refined existing single-cancer screening models in several ways, including a focus on incidence rounds.…”

“…Reducing this hazard to that of earlier stages (e.g., by early detection) could reduce 15% of total cancer mortality among persons aged 50-79. 9 These simple calculations underscored the burden of stage IV disease, but do not capture more sophisticated aspects of a potential multi-cancer screening strategy, including the published performance of blood tests across cancer types and stages, 5 as well as the preclinical sojourn time during which otherwise asymptomatic cancers might be detectable by such testing. Applying insights obtained from prior models of singlecancer screening paradigms (Supplementary Methods and Materials), we constructed a simple, efficient model for predicting diagnostic yield and stage of diagnosis due to screening with a MCED test, and the resulting potential effect on mortality across all cancer incidence.…”

Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set

“…Cancer will soon be the leading cause of mortality globally, and while development of more effective therapies is needed, 1 many may only prolong survival by a few months, if at all. 2 In addition to potentially reducing mortality, improving population-scale early detection also reduces disease-and treatment-related morbidity, [3][4][5][6][7][8][9][10] increases the likelihood of treatment success, 6,9 improves quality of life, 11 and reduces treatment cost and complexity. 6,11 Currently, only five cancer screening tests are available in the USA (breast, colorectal, cervical, lung, and prostate), collectively accounting for only 42% of annual cancer incidence in people aged 50-79 years.…”

“…29 It has been estimated that cancer detection before stage IV could reduce cancer-related deaths by !15% within 5 years. 7 A new approach called multi-cancer early detection (MCED) has the potential to achieve this goal by detecting signals for multiple cancers from cell-free DNA (cfDNA) or other circulating analytes in the blood shed by tumors. These assays use genomic sequencing or other approaches, sometimes in combination with machine learning to detect signals from cfDNA methylation, [30][31][32][33] mutations, 34,35 and/or fragmentation, 36 or other circulating analytes such as proteins.…”

Estimating the population health impact of a multi-cancer early detection genomic blood test to complement existing screening in the US and UK

“…1700 breast and 2400 bowel cancers) [24]. About 18% of all cancers are diagnosed at stage IV but they represent 45% of all cancer deaths [32]. Shifting stage at diagnosis from IV to I-III is estimated to reduce the cancer death rate by 15-24% [32].…”