Abstract
Circulating tumour DNA (ctDNA) liquid biopsy is increasingly proposed for solid tumour surveillance after curative-intent
treatment, on the premise that molecular recurrence can be detected before it is radiologically or clinically apparent. We review
the analytical validity evidence for tumour-informed and tumour-agnostic ctDNA assays separately, since the two approaches
differ materially in sensitivity and applicability, and then examine the narrower and more recent evidence for clinical utility --
whether acting on a molecular recurrence signal actually improves outcome rather than simply advancing the date of diagnosis.
Tumour-informed assays achieve materially higher sensitivity at low variant allele fractions than tumour-agnostic panels, and
lead time to radiological recurrence across reviewed studies ranged from two to eleven months, but randomised evidence that
intervening on a molecular-recurrence-only signal changes overall survival remains limited to a small number of tumour types.
We set out where the evidence currently supports clinical adoption of ctDNA surveillance and where analytical validity has
outpaced demonstrated clinical utility.
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