Adjuvant setting
Determines if the patient may have residual or recurrent disease. Use of Signatera after surgery to evaluate the need for adjuvant chemotherapy. Overview on the therapeutic scheme of the patient.
Signatera™ in clinical practice
Metastatic setting
Determines progression or response during treatment. Assess for MRD more accurately than current risk-assessment methods. Use Signatera to detect recurrence earlier while it may still be resectable, or to reduce false positive CEA results
Clinical applications of ctDNA testing across the patient journey.
Clinical applications of ctDNA testing for MRD assessment
Why Tumor-informed MRD?
Signatera Clinical Applications
Neoadjuvant response monitoring
Tailor neoadjuvant treatment or surgical strategies to a patient’s specific needs.
Postsurgical MRD assessment
Identify patients who may or may not benefit from adjuvant therapy.
Recurrence monitoring
Triage indeterminate nodules; rule in / rule out disease recurrence.
Assess treatment effectiveness
Monitor ctDNA kinetics (increase or decrease in ctDNA levels) to quickly identify if there is any response to treatment.
Signatera™ is the first ctDNA molecular monitoring tool that detects molecular residual disease (MRD)
Cell-free circulating tumor DNA (ctDNA) has emerged as a promising non-invasive cancer biomarker for monitoring disease status of cancer patients. It consists of short nucleic acid fragments released into the systemic circulation as a result of tumor cell apoptosis and/or necrosis, providing important information on the unique genomic profile of every neoplasia.
ctDNA is the physiological tool that enables the early detection of tumor cells following cancer treatment or surgical intervention, namely molecular residual disease. Its assessment is important when planning a course of treatment, evaluating its effectiveness, determining whether the cancer has returned, or making a prognosis.
Why is circulating tumor DNA (ctDNA) interesting for MRD assessment?
Every patient’s tumor has a unique molecular profile and a dynamic evolution.
Cancer cells release circulating tumor DNA (ctDNA) into the bloodstream that reflects each tumor’s unique genetic fingerprint.
ctDNA is a powerful tool that can be used to measure and assess the absence or presence of MRD based on the tumor’s unique molecular profile.
Dynamic real-time biomarker: the normal half-life is less than an hour.
Custom-built assay
Signatera™ is truly personalized
Based on the unique mutation signature of each patient’s tumor.
Identifies and tracks tumor mutations at the source.
Once a personalized assay is designed, a patient’s blood can be used to accurately monitor for the presence or absence of disease over time.
Tumor informed
Tracks 16 clonal variants based on whole-exome sequencing (WES) of tumor tissue and matched normal blood for each patient in order to identify specific DNA biomarkers of the tumor.
Sensitivity & Specificity
Signatera™ is optimized to detect extremely low quantities of ctDNA and determine the presence or absence of molecular residual disease.
Ultra-sensitive MRD detection at VAFs as low as 0.01% by tracking 16 ctDNA-specific markers (>99% of cases).
Clinical management and follow-up after Signatera™ testing
The first two scenarios are identified as high relapse risk.
Positive → Negative or decreasing positive
Intervention: Radiation / Chemotherapy. Interpretation: Likely response to treatment.
Positive → Increasing positive
Intervention: Targeted therapy / Immunotherapy. Interpretation: Less likely response to treatment.
Negative → Negative
Intervention: Observation. Interpretation: No residual disease detected. Continue to monitor.
Negative → Positive
Intervention: Observation. Interpretation: Molecular relapse detected.
Response monitoring
May be considered for select “watch and wait” patients to support a nonsurgical approach.
Postsurgical MRD assessment. Use Signatera™ after surgery to evaluate the need for adjuvant chemotherapy and potentially avoid unnecessary treatment
Recurrence monitoring- Use Signatera™ along with CEA testing to detect recurrence earlier while the tumor may still be resectable.
Assess treatment response. Signatera™ enables real-time monitoring of ctDNA kinetics for early and sensitive evaluation of treatment response.
Signatera™ accurately identifies patients at high risk of recurrence¹
Clinical evidence in colorectal cancer
Only 3% of patients who test negative will relapse.
MRD positive patients benefit significantly from adjuvant chemotherapy²
97%
High-risk pStage II
pStage III
pStage IV
W/ ACT / W/O ACT
HR / CI / p-values
Additional genomic profiling
Add the Altera™ tumor genomic profiling test when you order Signatera™ to get clinically relevant biomarkers (e.g., EGFR, KRAS, NRAS, BRAF, MET, MSI, TMB) and MRD monitoring with no additional sample.
Altera utilizes whole-exome and whole-transcriptome sequencing.
Add Empower hereditary cancer test to inform treatment options following a cancer diagnosis.
Additional clinical evidence in colon cancer
Relapse-free survival according to ctDNA status in colon cancer.
Colorectal Cancer References
Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5(8):1124–1131. doi:10.1001/jamaoncol.2019.0528.
Kotaka et al. Association of circulating tumor DNA dynamics with clinical outcomes in the adjuvant setting for patients with colorectal cancer from an observational GALAXY study in CIRCULATE-Japan. ASCO GI 2022.
Bladder Cancer
Response monitoring. Lack of ctDNA clearance during neoadjuvant treatment is a better predictor of recurrence than pathologic response.¹
Postsurgical MRD assessment. MIBC: Postcystectomy MRD assessment can help risk-stratify patients and identify those with evidence of residual disease who may benefit from adjuvant treatment,² including the recently approved nivolumab immunotherapy.³
Recurrence monitoring. MIBC: ctDNA can predict disease recurrence up to 245 days (median 96 days) before clinical / symptomatic progression to improve patient outcomes.¹
Assess treatment response. Monitor ctDNA kinetics serially to evaluate response to single agent immunotherapy (i.e., pembrolizumab, atezolizumab, nivolumab) and thus inform treatment duration. ctDNA clearance is associated with improved prognosis.⁴
Clinical evidence in muscle-invasive bladder cancer
Predictive evidence — IMvigor010
Inform treatment decisions postcystectomy.
IMvigor010 study background: Phase III, randomized clinical trial of atezolizumab vs observation in high-risk adjuvant MIBC.²
Prognostic evidence — Aarhus University
Monitor patients after definitive therapy.
Aarhus University bladder cancer study: 68 locally advanced MIBC patients with 656 plasma samples collected longitudinally with a median follow-up of 21 months.¹
Predictive and prognostic evidence
Overall survival by ctDNA status and relapse-free survival after cystectomy.
Predictive
ctDNA(+) after cystectomy may be predictive of treatment benefit with atezolizumab (OS HR = 0.59).
ctDNA(−) patients had similar OS on atezolizumab vs observation.
Prognostic
IMvigor010 confirmed the prognostic value of ctDNA status (Overall Survival HR = 8.00; 95% CI: 4.92–12.99; p < 0.0001).
Longitudinal testing in MIBC was highly prognostic with a hazard ratio of 129.6.
ctDNA demonstrated lead time to clinical recurrence of up to 245 days (median 96 days).
ctDNA at any time point after cystectomy was a stronger predictive factor of recurrence than lymph node status before cystectomy and pathologic response.
Signatera™ ctDNA analysis in MIBC
Signatera™ ctDNA analysis can help identify MIBC patients whose disease is likely to recur after cystectomy if not given further treatment.
Additional genomic profiling
Add the Altera™ tumor genomic profiling test when you order Signatera to get clinically relevant biomarkers (e.g., FGFR, ERCC2) and MRD monitoring with no additional sample.
Altera utilizes whole-exome and whole-transcriptome sequencing.