Why is Galleri's Stage I sensitivity only 16.8%?

Galleri's 16.8% Stage I sensitivity is a consequence of the fundamental limitations of cfDNA methylation detection at early disease stages. At Stage I, small localized tumors shed very small amounts of tumor-derived cfDNA into circulation — often below 0.1% of total circulating cfDNA. PCR-based amplification introduces enough variability that detecting this minuscule cancer fraction reliably is extremely difficult. The methylation pattern signatures of early-stage cancer are subtle and overlap significantly with normal tissue methylation variation. In contrast, miRNA overexpression in cancer cells is a strong, early biological signal that produces a large, clear difference in the HL ratio (1.83× vs 1.04×) even at Stage I — which is why the nanopore platform achieves 81–97% Stage I sensitivity while Galleri achieves 16.8%.