Assessing Potential Harms From Screening Overdiagnosis and False Positives With Multicancer Early Detection Tests

Multicancer early detection tests could be used for cancer screening, but may lead to harms, including false positive results and overdiagnosis of indolent tumors that would not have become clinically evident during that person's lifetime. We assessed the potential for these screening harms in the context of future population-based screening with a multicancer early detection test.

We used a microsimulation model to assess potential population-level impacts of screening at ages 50-75 years with a multicancer early detection test in Canada. We assumed high test specificity (97%-99.1%) and test sensitivity increasing with cancer stage. The model includes latent indolent cancers that would not be diagnosed within that person's lifetime but can be overdiagnosed through screen-detection. We calculated the yearly and cumulative lifetime probabilities of screening overdiagnosis and false positive test results, assuming a range of preclinical screen-detectable periods (2-5 years).

An estimated 2.1%-6.0% of all yearly screen-detected cancers with a multicancer screening test were predicted to be overdiagnoses across scenarios. The proportion of overdiagnosis varied by site and strongly increased with age, going from 1% at age 50 to over 10% of screen-detected cancers by age 75. The test positive predictive value ranged from 15.9% to 77.6%, meaning that there could be 0.3-5.3 false positives with no underlying cancer for every true cancer case detected by the test.

Population-level multicancer screening with a multicancer early detection test would lead to screen-related overdiagnosis; healthcare systems should consider how overdiagnoses and screening false positives may increase their follow-up capacity and caseload.