Patients with colorectal cancer may soon be able to rely on a blood test that detects tumor DNA to help determine the most effective treatment plan, according to a new study published last week in Nature Medicine. But experts have noted that additional evidence is needed before the test sees widespread adoption.
For the study, researchers administered Natera's blood test, Signatera, to 1,039 patients who had undergone surgery to remove stage II, III, and IV colorectal cancer. The researchers used the liquid biopsy to look for traces of circulating tumor DNA (ctDNA), which are deposited into the blood stream.
When the biopsy yields a positive result, it means there are residual cancer cells in a patient's body.
Roughly 18% of study participants tested positive for ctDNA when they were tested four weeks after surgery. Notably, the researchers found that the presence of ctDNA was the single largest predictor of cancer recurrence.
Patients with ctDNA in their blood were much less likely to have their cancer come back if they received chemotherapy. However, those without ctDNA who received chemotherapy under current guidelines saw no benefit from the treatment.
"What the study showed was that the people who had the liquid biopsy, or ctDNA, being positive after surgery, had an extremely, extremely high chance of recurrence...10 times higher risk compared to people who were ctDNA negative," said Suneel Kamath, a gastrointestinal oncologist at the Cleveland Clinic, who was not involved with the study. "What's interesting too was that was by far the strongest factor. We use a lot of other factors, like how progressive the tumor is and how many lymph nodes are involved."
Currently, the National Comprehensive Cancer Network (NCCN)—a network of cancer centers that sets treatment guidelines—recommends chemotherapy after surgery for all stage III patients and some stage II patients. NCCN advises against chemotherapy for stage I patients.
But this new study suggests liquid biopsies would provide oncologists with a more accurate indicator of which patients would benefit from chemotherapy, Kamath said.
According to the study authors, there are two primary benefits of using liquid biopsies to help inform cancer treatment. First, patients without ctDNA could safely skip chemotherapy with the knowledge that their cancer is unlikely to return. In addition, patients with ctDNA could receive the most beneficial treatments for their condition while being monitored to ensure those treatments are working.
"[This] field is really opening up personalization for millions of Americans who are diagnosed with early-stage disease," said Alexey Aleshin, one of the paper's authors and CMO of Natera.
Still, experts have noted that additional evidence is needed before liquid biopsies will become a standard part of cancer care.
"The impact of this individual paper should be taken into the context of other papers that have recently come out and are ongoing...It has a meaningful impact in allowing us to not only identify high-risk patients, but also showing that giving them chemotherapy after the surgery is beneficial," said Alok Khorana, director of the gastrointestinal malignancies program at the Cleveland Clinic, who was not involved in the study.
"The findings of this study are provocative, but not sufficient to just yet change clinical practice," Khorana said, "although I foresee that that's going to happen very, very soon in the near future."
"It is exactly the right next step in the direction of using [liquid biopsy] for treatment stratification," said Peter Kuhn, a cancer researcher at the University of Southern California, who was also not involved in the study. "Where it gets complicated has to do with [colorectal cancer] in particular and the question of what is sufficiently superior to modify current treatment paradigms," Kuhn noted.
However, "[t]he whole concept of how we stage and prognosticate cancer is really beginning to slowly shift," he added. "It's a big deal. It's already impacting how patients are being managed." (Kotani et al., Nature Medicine, 1/16; Nasser, ABC News, 1/16; Wosen, STAT+ [subscription required], 1/16)
A new paradigm for disease monitoring
Liquid biopsies have recently made splashy headlines as developers like GRAIL and Guardant Health promote their use in early cancer detection. But as articles like this one demonstrate, liquid biopsies may have even greater potential for use in treatment and recurrence monitoring.
At this point, the use of liquid biopsies for disease monitoring is not new. In fact, in our 2022 Cancer Market Trends, we identified liquid biopsies for disease monitoring as one of the clinical innovations with the greatest potential to change the cancer treatment paradigm. At the time of publication last spring, we were still waiting to see if adoption would take off.
Now, new evidence is making it clear that widespread adoption is coming—if not already here. At this point, many providers are already using liquid biopsies for disease monitoring. In fact, Natera (the maker of Signatera) reported that more than 25 percent of oncologists ordered its test in the fourth quarter of 2022. With the additional evidence of utility the Nature article provides, we can expect to see utilization grow even further, especially as more studies show results in other cancer types.
This has significant implications for cancer care providers and other industry stakeholders. Surprisingly, payment isn’t the biggest issue here, since there is already a precedent for payer coverage of blood tests that monitor disease progression (Signatera is covered by Medicare and many commercial health plans). But consistent use of liquid biopsies as part of the regular treatment pathway will require workflow redesigns, changes to clinical decision-making, and technology that can integrate test results into clinical practice as seamlessly as possible.
For patients, liquid biopsies for disease monitoring are a clear win. Unlike liquid biopsies for cancer screening, which are controversial and could pose an untenable cost to the US healthcare system, liquid biopsies for disease monitoring may end up falling under the wide umbrella of value-based care. Patients will avoid challenging and unnecessary rounds of chemo, while payers will avoid paying for it---all for the low list price of a couple thousand dollars, a fraction of the cost of chemo.
We’ll be watching to see if these results can be replicated in other tumor sites and disease stages. For more background on the use of liquid biopsies in cancer care, check out my report, liquid biopsies for early cancer detection and disease monitoring.
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