Multi-cancer early detection screening tools: A dream come true or a nightmare in the offing.

Abstract

e18926 Background: US cancer deaths were at 610,000 in 2022 with 1.9 million new diagnoses of cancer, 86% of which were patients over age fifty. Roughly 150,000 advanced cancers were diagnosed with five current screening techniques. That leaves 1.75 million cancers to be diagnosed symptomatically, largely in advanced stages. The dream is to screen in a minimally invasive fashion for multiple types of cancer at earlier, treatable, life-saving stages. The Galleri test claims to fulfill that dream by identifying more than fifty different cancers, and their location, using a blood test that captures ctDNA linked to aberrant methylation. As their dream approaches reality, with a dozen US hospital systems already offering Galleri, a fiscal and ethical nightmare is likely to ensue. We will demonstrate to providers that Galleri’s analytical validity and clinical utility is marginal at best – largely due to uncertainty surrounding the nature of those fifty malignancies. Methods: Systematic review of literature was performed across multiple databases using the key terms "Cancer Early Detection" AND OR "MCED" AND OR "GALLERI." Grail’s optimistic portrayal of the test’s current efficacy is largely derived from Hubbell and colleagues’ recent work modelling a Galleri-like test that claimed an achievable 24% reduction in cancer mortality (~150,000 lives). Critics contend that their assumptions are too optimistic. The natural histories of most of those fifty cancers are poorly understood, such as tumor latency periods, which means the cancer shift detection to an earlier stage is unknowable. Moreover, we cannot know whether these cancers would have been caught earlier, symptomatically, and successfully treated - which is true of 68% of diagnosed cancers. Etzioni and colleagues concluded that 6% of cancer deaths might be reduced by Galleri, despite that number is still uncertain and optimistic. Galleri cannot take credit for those saved lives. Results: GRAIL proposes population-based screening for 110 million Americans over age fifty annually at a cost of $950 per test. That would add over $100 billion per year to the health costs to discover no cancer in 99% of the persons tested. Roughly $50 billion would be added to Medicare program costs, now at $1 trillion. To save 18,000 Medicare lives would cost $2.8 million per life saved, a significant misallocation of Medicare resources, given many less costly opportunities to save more lives. Finally, individuals with marginal or no health insurance would be informed by Galleri they had an early-stage cancer unaffordable to treat. They represent statistically salvageable lives not actually salvaged, which is a presumptive injustice. This argument holds, despite the company’s pledge to reduce cost by over 40% over four years. Conclusions: In sum, Galleri, as a population-based cancer screening test, is not economically affordable, not ethically equitable, and only marginally medically beneficial.