Signatera for detecting molecular residual disease from solid tumour cancers

The technology described in this briefing is Signatera. It is used for measuring circulating tumour DNA (ctDNA) in the body to detect the presence of molecular residual disease (MRD) from solid tumours.

The innovative aspects are that Signatera is designed to detect and track tumour-specific clonal mutations with a low limit of detection. This may optimise sensitivity for more accurate MRD assessment.

The intended place in therapy would be in addition to standard care in people with solid tumour cancers. It can be used in the adjuvant setting to inform the need for additional treatment after surgery, and the surveillance setting to monitor for recurrence or assess therapy response.

The main points from the evidence summarised in this briefing are from 6 studies (4 prospective cohort studies, 1 phase 2 trial, and 1 secondary analysis from a randomised phase 3 trial) including 1,102 people with solid tumours. They show that Signatera improves prognostic assessment and may detect recurrence earlier than standard care alone. ctDNA testing with Signatera may also predict response to adjuvant treatment.

Key uncertainties around the evidence or technology are that there is no prospective evidence on using Signatera in clinical practice or its effect on treatment decisions or clinical outcomes.

Experts advised that there is not enough evidence to support routine use of the technology in the NHS. This is in line with recommendations from the European Society for Medical Oncology on the use of ctDNA. But there are several ongoing trials that may address gaps in the evidence.

The cost of Signatera is between £2,900 and £3,500 per test (excluding VAT). Costs may be offset if it reduces the use of adjuvant therapy or imaging. But some experts cautioned that they would not offer treatment without radiographic results, which could lead to increased imaging.