Mulitcancer Early Detection Tests Cut Stage IV Diagnoses by Nearly Half Over 10 Years

A microsimulation model evaluating the potential impact of supplemental multicancer early detection (MCED) testing found that annual screening could substantially reduce late-stage cancer diagnoses over 10 years, with stage IV cases declining by 45% compared with standard care alone.¹

The modeling study, which simulated 5 million US adults aged 50 to 84 years across 14 cancer types, showed a 10% increase in stage I diagnoses, 20% increase in stage II, and 34% increase in stage III, with the greatest absolute reductions in stage IV cases occurring in lung, colorectal, and pancreatic cancers, reported Jagpreet Chhatwal, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues in Cancer.¹

"Our study shows that MCED testing has the potential to substantially reduce stage IV cancer incidence, particularly for cancer types that lack routine screening programs," the team wrote. "Although further research is needed to validate these findings in real-world settings, our results suggest that MCED testing could transform cancer diagnosis and improve patient outcomes across a broad range of cancer types."¹

Half of cancer cases in the United States are detected at advanced stages,² yet routine screening is currently recommended for only 4 types (breast, cervical, colorectal, and lung)³ meaning roughly 70% of new cancer cases occur in types without available screening tests.⁴

Development of the Simulation Model for MCED

The researchers developed the Simulation Model for MCED (SiMCED), a continuous-time, discrete-event microsimulation incorporating 14 solid tumor types that collectively account for nearly 80% of cancer incidence and mortality: breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, kidney, liver, lung, ovarian, pancreatic, prostate, and urinary bladder cancers.¹

The model was developed to reproduce annual cancer incidence rates as reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2015 to 2021. The simulated cohort included 5 million adults aged 50 to 84 without a diagnosis of cancer with collective demographic characteristics conssitent with the 2015 US population.¹

A diagnosis of cancer could be the result of standar-of-care procedures (eg, routine screening, incidental detection, and symptomatic presentation) or of annual MCED testing. The model's base case assumed annual testing with 100% uptake and adherence.¹

A Closer Look at Stage IV Reductions

Breaking down the stage IV reductions by cancer type revealed important patterns, the authors pointed out. The largest absolute reductions occurred in lung cancer (400 versus 765 cases per 100,000), colorectal cancer (96 versus 236), and pancreatic cancer (89 versus 211). The largest relative reductions appeared in cervical cancer (83%), liver cancer (74%), and colorectal cancer (59%). When breast and prostate cancers, for which MCED sensitivities are relatively low, were excluded from the analysis, stage IV reduction increased from 45% to 50%.

Stage IV reduction proved higher for cancers with recommended screening programs (51%) compared with those lacking screening options (39%), suggesting MCED testing could both supplement existing screening and serve as the primary detection method for cancers currently without screening tests.

The cumulative increase in total diagnoses was modest at 2.8% (241 additional diagnoses per 100,000). Chhatwal and colleagues emphasized the the relatively small increase "mitigates concerns that MCED testing could lead to a surge in unnecessary cancer diagnoses and treatment," adding that "overdiagnosis may not be an issue with this [MCED] technology."

Among the study's limitations the authors acknowledged the uncertainty around epidemiological parameters such as disease dwell times and unobserved incidence, potential differences between controlled study conditions and real-world test performance, and the assumption that MCED availability would not affect standard screening uptake. The model also restricted individuals to developing only one cancer type per lifetime, potentially underestimating MCED's true benefit.

"Our study demonstrates that incorporating an annual MCED test into the SoC could lead to substantial downstaging of cancer stage at diagnosis over a 10‐year period, with a notable reduction in stage IV diagnoses," they concluded. "These findings have strong clinical implications because earlier stage diagnosis is associated with improved survival."

References

1. Chhatwal J, Xiao J, ElHabr AK, et al. The impact of multicancer early detection tests on cancer stage shift: A 10‐year microsimulation model. Cancer. 2025;e70075. doi:10.1002/cncr.70075
2. Crosby D, Bhatia S, Brindle KM, et al. Early detection of cancer.
   Science. 2022;375(6586):eaay9040. doi:10.1126/science.aay9040
3. Cancer Screening Tests. Centers for Disease Control and Prevention. October 17, 2023. Accessed November 13, 2025. https://
   www.cdc.gov/cancer/prevention/screening.html
4. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12‐49. doi:10.3322/caac.2182