Life can feel full of uncertainty when battling cancer, with few guarantees. “Is there still cancer in my body?” and “Will it come back?” are common questions that have long been difficult to answer confidently until recently. Advances in next-generation sequencing — and a growing understanding of how our bodies respond to illness and treatment — have brought us closer than ever to predicting our individual futures, at least when it comes to cancer.
In recent years, cancer researchers have embraced new noninvasive technologies that can detect small amounts of DNA shed by tumors into the blood, also known as circulating tumor DNA (ctDNA). This is no easy feat, as ctDNA is extremely scarce after surgery and treatment — as low as a single molecule in a tube of blood. But by broadly sequencing one’s tumor, we can identify its unique genetic signature, allowing for the creation of a highly sensitive and personalized assay that can track cancer in the body over time.
Today, this is commonly referred to as molecular residual disease (MRD) testing, and it’s quickly becoming an important tool to help oncologists inform their cancer patients’ treatment and answer questions about the road that lies ahead.
With MRD testing, a positive result means we can correctly identify who is likely to recur more than 98 percent of the time. Conversely, studies have shown that a negative result means a patient’s risk of recurrence is significantly reduced. Still, MRD tests are not being utilized enough. With roughly 35 percent of colorectal cancer patients alone eventually experiencing recurrence within five years, MRD tests must be regularly implemented into clinical practice so that more patients can have access to personalized treatment and care.
Recent regulatory moves have paved the way forward: MRD testing is now covered as reasonable and necessary for Medicare patients with a history of certain types of cancer such as colorectal cancer. The Centers for Medicare and Medicaid Services also recently issued a final local coverage determination to extend coverage for MRD testing to immunotherapy response monitoring. MRD testing in lung cancer, breast cancer, bladder cancer, esophageal cancer, and other types of cancer has been the focus of validation studies that could further expand MRD testing access for cancer patients.
Data generated across cancer types is showing MRD testing to be highly prognostic and predictive, proving just as precise — if not more so — than traditional diagnostic tools. Studies have shown that personalized MRD tests can detect cancer recurrence months, or even years, before radiologic imaging. And one recent study found that measuring how quickly ctDNA levels grow over time can help predict patient survival and aid oncologists in clinical decision making.
In addition, personalized MRD testing can help accurately determine if certain treatments like immunotherapy are working. Though roughly 200,000 people are on immunotherapy each year, less than a third of people will respond positively. With serial ctDNA testing, oncologists can identify early on who is most likely to benefit. This allows them to tailor the treatment plan accordingly, in partnership with the patient. For example, if personalized ctDNA testing indicates that a patient is not responding to therapy, the patient can be spared the expense and difficulties of continuing the treatment, and the patient can also be spared continued exposure to toxicities.
And for many cancer patients already experiencing the pain and anxiety associated with a cancer diagnosis, MRD testing can help further reduce the mental burden of uncertainty. Part of the true value of MRD testing, therefore, lies in the peace of mind it provides. And we’re finding that more and more patients want to know this information. Even when one tests positive for MRD, knowing this empowers them with the confidence to make the most informed treatment decisions possible for their care. It gives them that extra bit of reassurance and puts them back in the driver’s seat. It also often allows them to act early, improving the chances they will be able to successfully treat the cancer.
As we continue to actively research applications for MRD testing across various cancer types and generate data to support novel technologies that can detect ctDNA with extremely high levels of precision, we bring more answers and information to more cancer patients. Tumor-informed MRD testing gives us the opportunity to transform knowledge, diagnosis, and treatment, helping us push forward the field of personalized medicine and save lives.
Alexey Aleshin is a hematology-oncology physician and general manager of early cancer detection and interim head of medical affairs of oncology, Natera. He can be reached on Twitter @aaleshin.
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