Signatera: ctDNA Use in Cancer Monitoring Is Now Officially Recognized

Among tests developed to predict recurrence risk and monitor patients precisely, liquid biopsy includes the prominent Signatera test, which has reached an important milestone. Updated United States National Comprehensive Cancer Network (NCCN) clinical guidelines for colon cancer, rectal cancer and Merkel cell carcinoma (MCC) recognize circulating tumor DNA (ctDNA) as a prognostic biomarker for assessing recurrence risk.

ctDNA Testing for Prognosis and Postoperative Treatment Decisions

Circulating tumor DNA (ctDNA) testing is increasingly used to predict disease course and personalize postoperative treatment decisions. It offers greater sensitivity than conventional imaging for detecting residual disease and estimating recurrence risk. By providing critical information about whether additional treatment such as adjuvant chemotherapy is needed, it may prevent unnecessary treatment and enable more personalized care.

Related topic: What Is Minimal Residual Disease in Cancer, and How Can Liquid Biopsy Detect It?

Changes in NCCN Guidelines

• Colon and Rectal Cancer: NCCN identifies ctDNA as a high-risk factor for recurrence during adjuvant treatment after surgery. This marks the first official scientific recognition of ctDNA testing for predicting recurrence.
• Merkel Cell Carcinoma: Updated NCCN guidance for MCC refers to Signatera and recognizes its ability to assess disease burden and signal recurrence before it becomes clinically evident.
• Clinical Data: In 2024, Journal of Clinical Oncologypublished a prospective multicenter study finding 95% detection sensitivity in MCC and a 20-fold higher recurrence risk among patients with persistently positive Signatera results.

The BESPOKE CRC Study and Signatera in Colorectal Cancer

BESPOKE CRC evaluates Signatera-based ctDNA testing for minimal residual disease (MRD) in stage II/III colorectal cancer. It enrolled 1792 patients during 2020-2022, with data from 350 analyzed.

• Main Findings:
  • MRD Positivity:
    • All patients: 15.6% (46/295)
    • Stage II: 6.9% (9/130)
    • Stage III: 22.4% (37/165)
  • Effect on Disease-free Survival (DFS):
    • MRD+ patients had a 20-fold higher recurrence risk (HR=20.8, p<0.0001).
    • MRD+ patients receiving adjuvant chemotherapy had longer DFS than those not receiving it (18.7 vs. 6.7 months, HR=3.9, p=0.01).
  • ctDNA Clearance and Follow-up:
    • ctDNA cleared in 39.1% of MRD+ patients.
    • Those with clearance had longer DFS than those without it (24.2 vs. 13.8 months, HR=0.4, p=0.045).
    • However, 44.4% of MRD+ patients with clearance (8/18) became ctDNA+ again, detected before radiological recurrence.

Signatera's Role in Cancer Monitoring

Signatera is a personalized, tumor-specific liquid biopsy test that helps identify recurrence risk early, detect residual disease, and optimize treatment decisions.

It is currently available clinically and covered by Medicare for

1. colorectal cancer,
2. breast cancer,
3. ovarian cancer and
4. muscle-invasive bladder cancer patients.

What Does the New NCCN Decision Mean?

1. More Sensitive Monitoring: It has been recognized as much more sensitive than conventional imaging for identifying recurrence risk.
2. Official Guideline Inclusion: Inclusion of ctDNA testing in clinical guidelines will allow doctors to use it more widely in patient care.
3. Personalized Treatment: ctDNA-guided monitoring will make treatment more individualized and help avoid unnecessary chemotherapy.

Conclusions and Future Prospects

This NCCN-approved development opens the way for ctDNA testing to become standard in future cancer monitoring. New trials are already being designed to assess Signatera in broader populations beyond MCC.

ctDNA testing will play a growing role in monitoring and treatment decisions, offering patients better, more personalized options.