Medicare has approved coverage for Natera’s genome-based Signatera molecular residual disease (MRD) assay under LCD L38779, extending access to beneficiaries across six cancer indications. The coverage applies to colorectal, breast, bladder, ovarian, and lung cancers, as well as pan-cancer immunotherapy monitoring, aligning with the scope of Natera’s original Signatera test. This regulatory milestone positions the genome-enhanced version as a Medicare-reimbursed standard of care option for post-treatment cancer surveillance.
The coverage determination was anchored by robust evidence, leveraging over 100 published clinical studies validating Signatera, demonstrating Medicare’s confidence in the assay’s analytical validity. At the 2025 ASCO Annual Meeting, Natera presented pan-cancer data from 392 patients across more than 2,600 samples using Signatera Genome, reinforcing the clinical utility that underpinned the coverage decision. The genome-based assay utilizes Natera’s patented multiplex PCR-NGS technology for deep sequencing of targeted high-quality variants, offering enhanced sensitivity over traditional approaches.
“We are pleased to have Medicare coverage now in place for our genome-based Signatera assay, underscoring the clinical utility of our test, as well as its analytical and clinical validity,” said Matthew Mega, Natera’s senior vice president of market access. The approval addresses a critical gap in precision oncology, where MRD detection can identify microscopic disease recurrence months before conventional imaging, enabling earlier therapeutic intervention.
The coverage expansion represents significant market potential within Medicare’s oncology beneficiary population, estimated at over 3 million annual cancer diagnoses among eligible patients. Signatera’s personalized, tumor-informed approach creates individualized assays using circulating tumor DNA to monitor treatment response and detect recurrence earlier than standard surveillance methods. This regulatory win strengthens Natera’s competitive position in the growing $2.8 billion liquid biopsy market, particularly as healthcare systems increasingly adopt MRD testing for treatment optimization.
The Medicare decision validates the clinical and economic value proposition of genome-based MRD monitoring, potentially accelerating adoption among commercial payers and expanding access to precision cancer surveillance across broader patient populations.
