Intended use population
What is the OncoguardTM Liver solution?
The OncoguardTM Liver solution is an innovative offering to aid in the detection of hepatocellular carcinoma. Combining a blood test demonstrating high performance for the detection of early- and later-stage hepatocellular carcinoma with a patient engagement program aimed at helping patients follow through with ongoing testing, the OncoguardTM Liver solution offers a streamlined approach to hepatocellular carcinoma testing and support to help patients at risk.
What is the OncoguardTM Liver test?
The OncoguardTM Liver test is a simple, single blood test for the detection of biomarkers associated with hepatocellular carcinoma. The test uses a sophisticated algorithm that combines the analysis of methylated DNA markers (MDMs) and alpha-fetoprotein (AFP) with a patient’s biological sex to generate an easy-to-interpret qualitative result that can aid in the detection of hepatocellular carcinoma.
Who is the intended patient for the OncoguardTM Liver test?
The OncoguardTM Liver test is a blood-based test for the qualitative detection of biomarkers associated with hepatocellular carcinoma in serum and plasma derived from whole blood.
The test is intended as an aid in the detection of hepatocellular carcinoma for adults with liver cirrhosis and/or chronic hepatitis B (HBV) who are at risk for hepatocellular carcinoma. Biannual testing is recommended in patients at risk for hepatocellular carcinoma.1,2
The OncoguardTM Liver test was validated in patients at risk for hepatocellular carcinoma, including those with cirrhosis and/or chronic HBV.
Who is not an appropriate patient for the OncoguardTM Liver test?
Patients who are not currently recommended for hepatocellular carcinoma testing, such as those who are at average risk for hepatocellular carcinoma, are not the appropriate patients for testing with the OncoguardTM Liver test.
The OncoguardTM Liver test has not been validated in patients at risk for hepatocellular carcinoma who:
- Have Non-cirrhotic HCV, Non-cirrhotic NASH, Non-cirrhotic NAFLD
- Had hepatocellular carcinoma resected in the past
- Have transitioned gender using exogeneous hormone therapy
Patients who are or may be pregnant should not be tested with the OncoguardTM Liver test.
What are some factors that qualify a patient for hepatocellular carcinoma surveillance?
According to the American Association for the Study of Liver Diseases, patients are considered eligible for hepatocellular carcinoma surveillance if they are believed to have:3
- Cirrhosis of any etiology
- Hepatitis B, C
- Genetic hemochromatosis
- Stage 4 primary biliary cholangitis
- Alpha-1-antitrypsin deficiency
- Other cirrhosis
- Select chronic Hepatitis B carriers without cirrhosis
Can a patient assigned as intersex at birth use the OncoguardTM Liver test?
Currently, no. The assignment of male or female sex at birth is used to determine the OncoguardTM Liver test result. We do not currently have data on the performance of the OncoguardTM Liver test for patients assigned intersex at birth.
Can a patient on hormone therapy for a gender transition use the OncoguardTM Liver test?
Yes. A patient on hormone therapy can still use the OncoguardTM Liver test. We do not have data on the performance of the test in patients transitioning genders using hormone therapy. We will need to know the patient’s sex assigned at birth to determine their OncoguardTM Liver test result.
Baseline knowledge on Clinical Statistics terminology: Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), False Positive (FP), False Negative (FN).4
- Sensitivity (true positive rate): The proportion of persons with disease who have a positive test (positive test results among persons with disease).
- False Negative Rate (1 minus sensitivity): The proportion of persons with disease who have a negative test (negative test results among persons with disease).
- Specificity (true negative rate): The proportion of persons without disease who have a negative test (negative test results among persons without disease).
- False Positive Rate (1 minus specificity): The proportion of persons without disease who have a positive test (positive test results among persons without disease).
- Positive Predictive Value: The proportion of persons with disease among those with a positive test (disease present among those with positive test results).
- Negative Predictive Value: The proportion of persons without disease among those with a negative test (disease absent among those with negative test results).
What is sensitivity of the OncoguardTM Liver test?5
- The OncoguardTM Liver test is 88% sensitive for identifying hepatocellular carcinoma.
- The OncoguardTM Liver test is 82% sensitive for identifying early-stage hepatocellular carcinoma.
- The OncoguardTM Liver test is 94% sensitive for identifying late-stage hepatocellular carcinoma.
What is the false negative rate of the OncoguardTM Liver test?5
In the lab clinical validation study, the OncoguardTM Liver testing identified 88% of patients with cancer, which means that 12% with cancer tested negative with the OncoguardTM Liver test.
What is the OncoguardTM Liver test’s specificity?
The OncoguardTM Liver test's specificity is 87%.
What is the false positive rate of the OncoguardTM Liver test?
In the clinical lab validation study, the false positive rate of the OncoguardTM Liver test was approximately 13%, which means a positive result was returned although no presence of hepatocellular carcinoma was noted on imaging or on an imaging report.
How might I incorporate the OncoguardTM Liver test into my clinical workflow?
The OncoguardTM Liver test is intended as an aid in the detection of hepatocellular carcinoma for adults with liver cirrhosis and/or chronic hepatitis B who are at risk for hepatocellular carcinoma. Biannual surveillance is recommended in patients at risk for hepatocellular carcinoma.1,2 The OncoguardTM Liver test was designed to be highly sensitive, particularly in the detection of early-stage (BCLC stage 0, A) hepatocellular carcinoma, making it an innovative tool for use in biannual surveillance. The OncoguardTM Liver test was not validated in a direct comparison to or in conjunction with ultrasound. As an independent diagnostic assay the OncoguardTM Liver test achieved a 82% sensitivity for the identification of early-stage hepatocellular carcinoma, 94% for late-stage hepatocellular carcinoma with an overall sensitivity of 88%.5
Is the OncoguardTM Liver test FDA approved?
This test was developed, and its performance characteristics determined, by Exact Sciences. It has not been cleared or approved by the US Food and Drug Administration (FDA). This test is used for clinical purposes. It should not be regarded as investigational or for research. The test is performed at Genomic Health, Inc. (an Exact Sciences company) which is certified under the Clinical Laboratory Improvement Amendments (CLIA) and qualified to perform high complexity clinical laboratory testing.
Warnings and Precautions
What are the warnings and precautions for the OncoguardTM Liver test?
- The performance of the OncoguardTM Liver test has been established in a cross-sectional case control study. Longitudinal performance of the OncoguardTM Liver test (i.e., benefits and risks with repeated testing over an established period) has not been studied. Performance has not been evaluated in adults who have been previously tested with the OncoguardTM Liver solution. Non-inferiority or superiority of the OncoguardTM Liver test for hepatocellular carcinoma detection as compared to ultrasound has not been established.
- Guidelines for hepatocellular carcinoma testing recommendations do not recommend testing in individuals at average risk for hepatocellular carcinoma or those with Child Pugh C liver status unless the patient is eligible for a liver transplant.2 The decision to utilize the OncoguardTM Liver test should be made on an individualized basis.
- A negative OncoguardTM Liver test result does not guarantee absence of cancer. Patients with a negative OncoguardTM Liver test result should be advised to continue participating in a hepatocellular carcinoma testing program with a method and interval suitable for the individual. For persons at risk for hepatocellular carcinoma, a 3- to 6-month testing interval is suggested by AASLD guidelines.1,2
- The OncoguardTM Liver test may produce false negative or false positive results. A false positive result occurs when the OncoguardTM Liver test produces a positive result, even though a contrast-enhanced CT or MRI will not find cancer. A false negative result occurs when the OncoguardTM Liver test does not detect a cancer even when a contrast enhanced CT or MRI identifies the positive result.
- Patients should not provide a sample for the OncoguardTM Liver test if they are pregnant or believe they are pregnant. The OncoguardTM Liver test includes a measurement of AFP, which may be elevated during pregnancy.4
- OncoguardTM Liver test results should be interpreted with caution in patients with congenital disorders of the reproductive system or patients undergoing gender reassignment exogeneous hormone therapy as the performance of the test has not been validated in this population.
- To ensure the integrity of the sample, our laboratory must receive the patient specimens within 5 days of collection. Providers should send specimens to our laboratory the same day specimens are collected, according to the instructions stated in the OncoguardTM Liver test Specimen Collection Guide (OncoguardLiver.com/resources).
Account Setup, Test Ordering, and Supplies
How do I get set up to start using the OncoguardTM Liver test?
How do I order a test?
Once you set up an account with Exact Sciences, we can get you supplies. Then, the OncoguardTM Liver test can be ordered by fax with a requisition form or electronically through the EpicCare® LinkTM portal. EpicCare® LinkTM is a secure, online tool for healthcare professionals and support staff registered with Exact Sciences Laboratories. Log into EpicCareLink.ExactSciencesLabs.com to order a test or request access if you do not already have an account.
Are there any special supplies needed to perform the OncoguardTM Liver test?
Yes. The OncoguardTM Liver test requires the Exact Sciences Blood Collection Kit to transport the collected specimens to the performing laboratory. The Blood Collection Kit contains the appropriate tubes and packing materials needed for specimen collection and shipment.
Are special specimen collection tubes required for the assay?
Yes. The Blood Collection Kit contains one BD Vacutainer® SSTTM tube and two LBgard Blood Tubes. The LBgard tubes contain a special preservative which stabilizes the specimen during transport. One 7.5 mL BD Vacutainer® SSTTM tube and two 8.5 mL LBgard Blood Tubes are required to generate a usable blood sample. We cannot accept other tubes to perform the test.
Should the Blood Collection Kits and tubes be stored in the refrigerator or freezer?
No. The Blood Collection Kits and tubes must be stored at room temperature (15-25 °C, or 59-77°F). Please do not store the Blood Collection Kit or tubes in the refrigerator or freezer. After collection, ship specimens in the Blood Collection Kit, which includes two temperature-controlled gel packs to maintain the appropriate temperature.
How do I get supplies?
What sample types are used for testing?
The OncoguardTM Liver test uses serum from the BD Vacutainer® SSTTM tube for the analysis of alpha-fetoprotein (AFP) and plasma from the LBgard Blood Tubes for the analysis of methylated DNA markers (MDMs).
How much blood is required to do the testing?
One 7.5 mL BD Vacutainer® SSTTM tube and two 8.5 mL LBgard Blood Tubes are required to generate a usable blood sample. It is very important to completely fill all blood tubes to ensure appropriate volume for testing. NOTE: The two LBgard tubes must be completely filled. The SST tube can be partially filled if there is a concern about being able to collect sufficient sample volumes.
Do I need to fill the tubes in a particular order?
Yes. The BD Vacutainer® SSTTM tube must be the first tube collected, followed by the two LBgard Blood Tubes.
Must the blood draw be performed on a particular day of the week?
Blood can be drawn any day of the week, but our laboratory does not receive shipments on weekends and Holidays. Thus, it is recommended that you collect specimens Monday-Thursday only. For specimens collected Monday-Thursday please ship on the same day as specimen collection for Priority Overnight delivery via the shipping vendor indicated on the pre-paid shipping label on the kit.
After collection, how much time does a sample have to get back to the lab?
To ensure the integrity of the sample, the laboratory must receive the patient specimens within 5 days of collection. Providers should send specimens to our laboratory the same day specimens are collected.
I collected the blood sample on Friday, Saturday, Sunday or Holiday. Is it OK to ship it on the day of collection?
May I label the tubes with a label from my in-house EMR system?
- Yes. As long as the label includes the patient’s first and last name, date of birth, and the date and time of specimen collection. If using the label from your EMR, please ensure that the label is placed lengthwise on the tube over the existing tube label. Ensure that the label is straight and that there is space on the tube for laboratory personnel to see the volume of blood in the tube.
- Please remember, the Blood Collection Kits and tubes must be stored at room temperature (15-25 °C, or 59-77°F). Do not store the Blood Collection Kit or tubes in the refrigerator or freezer. After collection, ship specimens in the Blood Collection Kit, which includes two temperature control gel packs to maintain the appropriate temperature.
Should the specimen collection tubes be shipped with an ice pack or in dry ice?
No. The specimens should be shipped in the Blood Collection Kit which includes two temperature control gel packs. DO NOT REMOVE these gel packs from the kit. Do not use any other ice packs or dry ice for shipping specimens to the laboratory. Only ship specimens in the Blood Collection Kit with the temperature-controlled gel packs included.
Will the specimen be OK to ship during extreme weather?
Yes. If the specimens are shipped in the Blood Collection Kit with the two temperature-controlled gel packs included.
What is the shelf life of the Blood Collection Kit, the LBgard Blood Tubes and BD Vacutainer SST tubes in the Blood Collection Kit?
Each blood collection tube has an expiration date printed on it. Please only submit specimens in non-expired Blood Collection Kits and blood collection tubes.
Are the specimen collection kit boxes reused for future orders?
Components of the Blood Collection Kit are eligible for reuse. No components will be reused if they have been contaminated by blood during shipment to the laboratory.
Are there medications, foods, or other substances that interfere with the assay?
There are no known interfering substances with the OncoguardTM Liver test.
Is the patient required to fast before blood collection?
No. The patient is not required to fast before collection.
Where can the patient get their blood drawn?
Blood can be drawn in your own practice by a healthcare professional with basic phlebotomy skills or at a laboratory affiliated with your practice (when contracted to do so).
Can my Quest or LabCorp phlebotomist draw blood for this test?
Exact Sciences does not have a negotiated contract with Quest or LabCorp for phlebotomy services to support the OncoguardTM Liver test.
How do I receive the results?
Results can be accessed in the EpicCare® LinkTM portal typically within a week from receipt of the specimens at Genomic Health, Inc, an Exact Sciences company. You will receive email notifications when results are available. To access results, log into EpicCare® linkTM at EpicCareLink.ExactSciencesLabs.com. It is the responsibility of the provider to notify patients of their results.
What is the turnaround time to receive results?
Results are typically reported within a week from the receipt of the specimens to our laboratory.
How are results reported?
What happens if the specimen cannot be processed or a valid result is not obtained?
If the sample cannot be processed, or if an invalid result is obtained, a new sample will be requested.
What does a positive OncoguardTM Liver test result mean? How do I counsel my patient?
A positive result does not necessarily mean that the patient has cancer. It means that the OncoguardTM Liver test detected elevated levels of methylated DNA markers and/or AFP in the blood, which are associated with hepatocellular carcinoma. False positives and false negatives occur with the OncoguardTM Liver test and appropriate clinical follow-up is important. Patients with positive results should follow up with diagnostic multiphase CT or MRI.
What does a negative OncoguardTM Liver test result mean? How do I counsel my patient?
- A negative result means that the OncoguardTM Liver test did not detect significant levels of methylated DNA markers and/or AFP in the blood which are associated with hepatocellular carcinoma. False positive and false negative results occur with the test.
- Patients with negative results should continue in surveillance programs appropriate for the patients. Guidelines recommend testing intervals of 3-6 months for patients at risk for hepatocellular carcinoma. Following a negative result, the patient may be retested with the OncoguardTM Liver test in 6 months.1,5
- A negative result indicates a low likelihood that hepatocellular carcinoma is present. The chance that a person with a negative OncoguardTM Liver test has hepatocellular carcinoma is less than 1 in 300 (negative predictive value 99.7%). These data are based on a case-control study of individuals at high risk for hepatocellular carcinoma and an estimated 2% prevalence rate within the at-risk population.
Can I receive the OncoguardTM Liver Test Composite Score?
The OncoguardTM Liver test was designed as a qualitative test to provide a positive or negative test result. A positive result occurs when the composite score is above or equal to the cutoff threshold. A negative result occurs when the composite score is below the threshold. The OncoguardTM Liver Composite Score has not been validated to linearly correlate with disease stage nor has the longitudinal performance of the OncoguardTM Liver test been established. However, should a provider want additional information regarding their patient’s result, a call with a Clinical Consultant can be scheduled by calling our Customer Care Center at 1-844-870-8870.
Can the healthcare provider receive individual biomarker results?
- No. The DNA biomarkers in the OncoguardTM Liver test do not have individually validated reference ranges, and each marker’s clinical significance is influenced by the other markers. Therefore, the DNA biomarker levels cannot be interpreted separately and are not reported separately.
- The AFP measurement is not reported independently.
Is it possible for alpha-fetoprotein (AFP) itself to drive a positive result from the algorithm, in the absence of any elevated DNA biomarkers?
- The OncoguardTM Liver test algorithm must incorporate all biomarker measurements to produce a result.
- The DNA biomarkers or AFP biomarker may trigger a positive result if sufficiently elevated relative to the reference marker.
- A positive result indicates that the biomarker combination has an increased association with hepatocellular carcinoma.
- Any positive result should be followed by a diagnostic multiphasic CT or MRI.
Is the alpha-fetoprotein (AFP) component of the OncoguardTM Liver test different from commercially available AFP test?
The AFP assay utilized in the OncoguardTM Liver test is an electrochemiluminescence immunoassay but is not designed or validated to be reported independently.
If a valid result is not available from any of the DNA or alpha-fetoprotein (AFP) components (due to not enough material/degraded sample/not returned/etc.), are the results of the other components reportable?
Valid results for all biomarkers must be available to generate the OncoguardTM Liver test result. Only the combined qualitative test result, as a positive, negative, or invalid, is reported.
Interpretation of results
Is additional follow-up necessary for a patient who has a positive OncoguardTM Liver test followed by a negative CT/MRI scan?
- Patients with a positive OncoguardTM Liver test and negative multiphase CT or MRI should remain on a testing interval that is appropriate for the patient
- National clinical guidelines recommend that a negative multiphase CT or MRI be followed by repeat testing at an interval and method that depends on the observation categorization.3
Patient Engagement Program
What is the Patient Engagement program included as part of the OncoguardTM Liver solution?
The OncoguardTM Liver Patient Engagement program includes patient support tools and provider reports that you can implement in your practice to help patients stay up to date with their recommended hepatocellular carcinoma testing.
What Patient support tools are available?
- Patient educational materials about liver disease, hepatocellular carcinoma (HCC), and the importance of routine hepatocellular carcinoma testing are available for you to provide to your patients during office visits.
- Care Navigators are available to contact patients after an OncoguardTM Liver test has been received in the laboratory to help them understand the testing process.
- Additional educational materials will be sent to patients after a negative test result to help them understand the importance of regular testing.
- Reminders will be sent to patients when they are due for their routine testing to encourage them to reach out to you to guide them on scheduling or following through with testing.
What Provider resources are available?
- Easily accessible reports with information on patients who have been tested and may be due for testing to help improve patient care.
- Dedicated account managers are available to answer questions about the OncoguardTM Liver solution and provide support with test ordering, results, or ordering supplies.
Coverage and Billing
Is the OncoguardTM Liver test covered by insurance?
- At this time, the OncoguardTM Liver test is not covered by most major insurers, including Medicare, Medicare Advantage, or Medicaid.
- We know that coverage for liver cancer testing is vital to ensuring you have access to the quality information you need about your patients’ health.
- We are working with insurance companies on an ongoing basis to gain coverage, and more information will be provided as coverage expands.
Is prior authorization required for this test?
Yes. Please obtain prior authorization for the test following the processes established by your patient’s lab benefit manager. We've provided an OncoguardTM Liver test Statement of Medical Necessity to assist your practice in obtaining a prior authorization for the test.
Is an Advance Beneficiary Notice (ABN) required for this test?
How much will my patients have to pay for this test?
- Out-of-pocket costs for the OncoguardTM Liver test will vary based on a patient’s specific health plan coverage policies, co-pays, and deductibles.
- Please call our Customer Care Center at 1-844-870-8870 with questions about coverage and billing for the OncoguardTM Liver test. Our specialists can help advise patients on the right questions to ask their carrier.
What options are available for patients who cannot afford to pay for the test?
Patients who receive a bill with out-of-pocket responsibilities for the OncoguardTM Liver test are encouraged to call 1-844-870-8870 and speak with a member of our Customer Care Center to learn about the support we offer, including coverage appeals support, payment plans, or potential eligibility for our Patient Assistance Program.