Plasma DNA Is More Reliable than Carcinoembryonic Antigen for Diagnosis of Recurrent Esophageal Cancer

Background
Carcinoembryonic antigen (CEA) and plasma DNA are known to be elevated in patients with esophageal cancer and are higher in patients with disseminated disease. The sensitivity and specificity of these markers in the diagnosis of recurrent esophageal cancer have not been compared.
Study Design
Plasma DNA was measured using polymerase chain reaction in 45 patients with esophageal cancer and 44 asymptomatic volunteers. The 95th percentile (19 ng /mL) in the volunteers was used to define normal. Thirty-nine patients had localized cancer and underwent resection, and six had disseminated disease at operation. Plasma DNA was measured preoperatively in all patients, with serum CEA measured in 31. Plasma DNA was measured sequentially during followup in 21 patients, including 7 who developed recurrence. CEA was measured in 14 of 21 patients who had sequential plasma DNA measured and in 6 of 7 patients with recurrence. CEA levels greater than 5.0 ng/mL were used as cut-off.
Results
Plasma DNA was more sensitive than CEA for detecting unresectable esophageal cancer (100% versus 40%), but it had a lower specificity (22% versus 89%).The positive predictive value (19% versus 40%) and negative predictive value (100% versus 89%) were similar for plasma DNA and serum CEA, respectively.
Plasma DNA was also more sensitive than CEA in detecting recurrent esophageal cancer (100% versus 33%). The specificity and positive predictive values were 100% for both tests, but the negative predictive values were higher for plasma DNA. Plasma DNA rose before there was clinical evidence of recurrence in 67% compared with only 17% for CEA.
Conclusions
Elevated plasma DNA is an extremely reliable indicator of the presence of recurrent disease, and, in the majority of patients, it rises before clinical evidence of recurrence. In contrast, a normal CEA should be interpreted cautiously, because it does not exclude recurrent disease.