Most patients with colon cancer — depending on staging — receive surgery to remove the primary tumor, along with adjuvant chemotherapy, explains Anne Marie Lennon, who directs Johns Hopkins’ Division of Gastroenterology and Hepatology. Patients with stage 1 cancer rarely receive chemotherapy because the risk of recurrence is so low; those with stage 3 cancer nearly universally receive chemotherapy because recurrence risk is high.
But chemotherapy for patients with stage 2 cancer, in which tumors invade the colon wall but don’t extend to lymph nodes or other organs, remains controversial. Although 80% of patients are cured just with surgery, cancer will recur in the remaining 20% without chemotherapy. There are some existing biomarkers that distinguish these two patient populations, Lennon says, but they are imperfect, leaving many patients to receive unnecessary chemotherapy that comes with significant side effects.
“It’s a clinical management dilemma. Do you give patients chemotherapy to try to make sure they’re cured, recognizing that the vast majority will not need it? Or do you take a chance and not give chemotherapy, knowing that patients’ prognosis will be far worse if their cancers do recur?” she says. “We need a better risk marker to get this right.”
Results from a recent study by Lennon and Johns Hopkins colleagues Bert Vogelstein, Kenneth Kinzler and Nickolas Papadopolous, along with colleagues at the Walter and Eliza Hall Institute of Medical Research in Australia, suggest that circulating tumor DNA (ctDNA) could be the marker that doctors have been waiting for.
The team worked with 455 patients diagnosed with stage 2 colon cancer. Care for about two-thirds of these patients was guided by their ctDNA: By seven weeks after surgery, 302 patients received a blood test that looked for evidence of ctDNA with the same mutations detected in samples taken from their tumors. If this ctDNA was present, they received chemotherapy — and if it wasn’t, they didn’t. The other 153 patients received standard management, including chemotherapy if their physicians recommended it.
Using ctDNA as a risk marker for recurrence cut the number of patients who received chemotherapy by half, from nearly 30% to just over 15%. Even though far fewer patients in the ctDNA group received this adjuvant treatment, two- and three-year survival rates were the same between patients in the ctDNA and standard care groups.
These results provide the first evidence that ctDNA may be safely used to guide treatment decisions for patients with stage 2 colon cancer, Lennon says — a finding that she says raises the potential for using this approach with other stages and cancer types as well. Future studies using this marker to help guide management will focus on early-stage pancreatic cancer and stage 3 colon cancer.
“One reason I work at Johns Hopkins is to be involved in research that improves the way we care for patients,” Lennon says. “This research has the potential to change the standard of care for thousands of patients every year.”
To refer a patient to the Johns Hopkins Division of Gastroenterology and Hepatology, call 410-933-7495.