Circulating tumor DNA (ctDNA) could be used to predict disease recurrence in patients with nonmetastatic colorectal cancer (CRC), according to investigators following an observational study.
About three out of four patients with a positive ctDNA test went on to have disease recurrence, reported lead author Yuxuan Wang, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, and her colleagues. On average, positive tests preceded clinical and radiologic evidence of recurrence by 3 months.
“[T]he optimal protocol for surveillance of resected colorectal cancer remains uncertain,” the investigators wrote in.
“The only recommended blood marker for CRC surveillance is serum [carcinoembryonic antigen (CEA)], an oncofetal protein that is elevated in the serum of patients with a variety of disease conditions, including CRC. Unfortunately, its utility is limited by the lack of sensitivity and specificity.” Although computed tomography and magnetic resonance imaging can improve disease detection, these techniques also have their own shortcomings, the investigators noted, setting the stage for the present study.
The investigators recruited 63 patients with stage I, II, or III CRC who underwent surgical resection in Sweden between 2007 and 2013. Blood samples for ctDNA testing were collected 1 month after surgery, then every 3-6 months. CT was performed every 6-12 months. During this process, 5 patients were excluded, leaving 58 patients in the final dataset, 18 (31%) of whom received adjuvant chemotherapy. Patients were followed until metastasis or a median of 49 months.
Among all patients, 13 tested positive for ctDNA, and 10 of these relapsed (77%), with a median time of 3 months between ctDNA positivity and CT or clinical evidence of recurrence. Three of the 48 patients (6%) who did not relapse had a positive ctDNA result that later dropped to an undetectable level. Of the 45 patients who tested negative for ctDNA, none had recurrence, although 1 was positive for CEA.
Results were also divided into patients who received or did not receive adjuvant chemotherapy. Among the 40 patients who did not receive chemotherapy, 8 had disease recurrence after a positive ctDNA test, although only 5 tested positive for CEA. Among the 18 patients who did receive chemotherapy, 2 tested positive for ctDNA and later relapsed, although only 1 tested positive for CEA. These figures translated to a ctDNA sensitivity for recurrence of 100%, compared with 60% for CEA testing.
“Serial ctDNA levels during follow-up can precede disease recurrence prior to routine radiographic imaging,” the investigators concluded. “Because ctDNA measurements can be obtained from blood samples collected during routine follow-up, they may be easily incorporated into routine follow-up to complement a CEA test, radiographic imaging, and other conventional modalities to help stratify patients on the basis of the risk of disease recurrence. Such a personalized surveillance strategy may allow for earlier detection of relapse and minimize unnecessary testing.”
The study was funded by the Virginia and D.K. Ludwig Fund for Cancer Research, the Commonwealth Foundation, the John Templeton Foundation, and others. The investigators reported financial relationships with PapGene, Sysmex, Eisai, and others.
SOURCE: Wang et al. JAMA Onc. 2019 May 9.