Watch the full episode on Youtube
In the world of health and wellness, the phrase “early detection” is incredibly powerful, especially when it comes to cancer. We know that diagnosing cancer at an earlier stage generally leads to better outcomes. While standard screenings like colonoscopies and mammograms are vital tools for specific cancers, many others are often only found when symptoms appear. This makes the concept of a simple blood test for early detection incredibly appealing.
Today, we’re drawing insights from a conversation between Freddie Kimmel and Dr. Joshua Routh from the YouTube video titled “How Liquid Biopsy and Epigenetics Help in Early Cancer Detection – Dr. Joshua Routh Interview”. They discussed EPISEEK™, a multi-cancer early detection liquid biopsy test.
What is EPISEEK™ and How Does It Work?
According to Dr. Routh, EPISEEK™ is a test that looks at a patient’s blood sample to find evidence of cancer. The core idea is that as cells in your body grow and die, they release their DNA into the bloodstream. Since cancer cells tend to multiply more than other cells, they also release DNA into the blood when they die. This circulating DNA is known as cell-free DNA (cfDNA).
The lab process involves taking a blood sample, removing the cells to get the plasma (the cell-free part), and then isolating the DNA from that plasma. However, detecting DNA alone isn’t enough because normal cells also release DNA. The critical step, as explained by Dr. Routh, is determining whether the DNA comes from healthy cells or cancer cells.
EPISEEK™ focuses on epigenetic markers, specifically methylation. Methylation is a natural chemical process where a methyl group attaches to DNA, often at specific sites (like 5-cytosine methylation in humans). In a healthy body, epigenetics, including methylation, helps turn genes on and off appropriately, allowing different cells (like neurons and skin cells) to have different functions despite sharing the same genetic blueprint. However, cancer is considered an epigenetic-based disease where abnormal methylation patterns can switch genes on or off in ways that promote out-of-control growth and alter cell behavior. Dr. Routh also mentioned that aging is likely a methylation-related process.
To detect these abnormal methylation patterns, the EPISEEK™ lab uses a chemical process called bisulfite conversion. This process changes the DNA based on its methylation status. Then, techniques similar to PCR (polymerase chain reaction), familiar to many from COVID testing, are used to amplify or make copies of DNA that has the methylation patterns characteristic of cancer. This amplified DNA is then analyzed using computer software and machine learning. Dr. Routh noted that PCR technology can work with small and damaged pieces of DNA, which is common for cfDNA in early-stage cancer, potentially giving it an advantage over sequencing technology that often needs more pristine DNA.
Understanding the Results and the Next Steps
The test results are simplified into two main outcomes: “cancer signal not detected” or indicating an “abnormal methylation signature”. Because this is a relatively new type of test, the lab actively supports ordering physicians and sometimes patients to discuss positive results and determine appropriate follow-up steps.
When discussing the likelihood of results, Dr. Routh used the example of testing a thousand people. He estimated that in such a group, perhaps half a percent to one percent might currently have cancer. Out of those thousand, about five people might receive a positive test result and be found to have cancer upon further investigation. However, about five others might also have a positive result, but no cancer is found during workup – what’s known as a false positive. While a roughly 50/50 positive predictive value for a positive result “doesn’t sound great,” Dr. Routh explained it’s seen as a necessary trade-off for the ability to detect cancers earlier than might otherwise be possible.
Who is This Test For?
Dr. Routh suggested the test is generally more beneficial for individuals who are more likely to have cancer. This includes people aged 50 and above, where cancer risk increases significantly. However, he noted that individuals in their 40s, 30s, or even 20s can consider the test, particularly if they have risk factors such as a strong family history of cancer, known genetic mutations like Lynch syndrome, or certain work exposures.
Freddy and Dr. Routh both emphasized that getting the test is a personal choice. While finding cancer early offers the best chance for successful treatment, the potential stress of a false positive is real. However, they agreed that the stress of dealing with a potential early detection scenario is far less upsetting than facing a late-stage diagnosis discovered only after symptoms appear.
Dr. Routh mentioned that detecting certain cancers, like prostate cancer and breast cancer, can be more difficult with this DNA-based method because they may not release as much cell-free DNA. However, the test looks for a general cancer signature, not specific cancer types, and has successfully detected cancers like stomach, bladder, and kidney cancers.
Practical Considerations
The current list price for EPISEEK™ is around $699. As of the discussion, insurance does not currently cover any multi-cancer early detection tests. The lab hopes to make the case for insurance coverage in the future, and the use of more accessible technology like PCR (compared to expensive sequencing equipment) is part of the effort to potentially reduce costs over time.
If an abnormal result is detected, the next steps involve working closely with your doctor. This typically begins with a thorough medical history and physical examination. Often, the next step is imaging, frequently a PET CT scan, which looks for both structural abnormalities (CT) and areas of abnormal sugar metabolism often found in cancer cells (PET).
The test is not recommended for individuals under 18. While no false positives have been reported in pregnant individuals yet, pregnancy involves significant epigenetic changes that could potentially interfere with the test’s specificity, so it’s recommended to wait until after delivery.
EPISEEK™ requires a physician’s order and is not available directly to patients without one. This is to ensure proper medical guidance and follow-up for the results. Dr. Routh stressed that this test is an add-on to existing standard cancer screenings (like colonoscopies and mammograms), not a replacement for them.
In summary, as discussed by Dr. Routh and Freddy, the EPISEEK™ test represents an innovative approach to potentially detecting multiple cancers earlier through the analysis of epigenetic changes in cell-free DNA found in the blood. It’s a new tool in the fight against cancer, offering a promising possibility for earlier intervention for many cancers that currently lack routine screening methods.