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.
Liquid biopsies can help inform treatments and predict colorectal cancer recurrence
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)