I had 4 years of post-op Signatera ctDNA blood draws (every 3 months). Ok... not yet FDA approved, so buy-in by oncologists and insurance companies is a bit iffy across America. I'll simply attach what AI says, in comparing basic NGS testing vs personalized Signatera (and Tempus) type ctDNA testing. Read on...

Signatera-type blood tests and general next-generation sequencing (NGS) liquid biopsies are not equivalent in how they approach, nor in their accuracy for, detecting real-time cancer recurrence.
While both are NGS-based technologies that look for circulating tumor DNA (ctDNA) in the blood, they serve different purposes:
Signatera-type tests (Tumor-Informed): These are personalized, "bespoke" assays that analyze a patient's own resected tumor tissue to create a custom test targeting the specific, unique mutations of their cancer.
General NGS Tests (Tumor-Naive/Plasma-Only): These use a standardized, pre-designed panel of genes to look for common mutations across a cancer type without needing the patient's original tumor tissue.
Here is a breakdown of why they are not equivalent:
Key Differences
Sensitivity (Precision): Because Signatera uses a personalized "fingerprint" of the tumor, it is designed to be far more sensitive for detecting Molecular Residual Disease (MRD)—the tiny amounts of cancer left after treatment.
Tumor-Informed vs. Naive: Signatera selects the top 16 most clonal (dominant) mutations from the patient's own tumor, whereas standard NGS panels are not personalized.
Speed of Detection: Studies show Signatera can detect molecular recurrence months before it becomes visible on conventional imaging scans (CT/MRI).
Comparison Table: Signatera vs. Generic NGS Liquid Biopsy
Feature Signatera-type (Tumor-Informed) Generic NGS (Tumor-Naive/Panel)
Method Personalized: Analyzes tissue + blood Standardized: Only blood
Sensitivity Very High (designed for MRD) Lower (less effective for tiny amounts)
Focus Tracking unique tumor mutations Scanning for common mutations
Main Use Long-term surveillance/recurrence Initial treatment selection/diagnosis
False Positive Rate Extremely Low (< 1-2%) Higher
Summary for Real-Time Recurrence
For monitoring for recurrence, Signatera-type tests are considered superior to generic NGS panels because they are specifically tailored to the patient’s unique genetic signature, which increases the likelihood of detecting recurrence, or "molecular residual disease" (MRD), much earlier.
A positive result on a Signatera test suggests a very high likelihood (98% or more) that cancer has returned or is still present, often long before traditional imaging can see it.