A retrospective study finding a 49% false-positive of carcinoembryonic antigen (CEA) testing among patients with a history of resected colorectal cancer, “suggests that confirmation of an ongoing increase in CEA level should be universal practice before an extensive workup is initiated,” Anya Litvak, MD, and colleagues from Memorial Sloan Kettering Cancer Center (MSKCC) reported in the Journal of the National Comprehensive Cancer Network.
The study involved 728 patients at Memorial Sloan Kettering who underwent resection for stage I, II, or III colorectal cancer between 2003 and 2012, and who had an increase in CEA level above the normal after a normal perioperative CEA level. “Of these, 358 had a false-positive elevation of CEA level, 335 had a true-positive elevation indicative of recurrent [colorectal cancer], and 35 had a true-positive elevation indicative of the development of a new, [non–colorectal cancer] malignancy,” the researchers found.
“For the purposes of this analysis, a false-positive was described as a CEA level higher than the upper range of normal (ie, ≥ 5.1 ng/mL) with no evidence of cancer on either imaging studies or other diagnostic procedures, with either follow-up of (1) at least 1 year since the first abnormal CEA or (2) abnormal CEA elevations followed by spontaneous normalization, with at least 2 consecutive subsequent normal CEA measurements in the absence of a therapeutic intervention,” they explained.
Among patients with false elevations, “111 had a single isolated CEA level elevation (median highest CEA level of 5.5 ng/mL) with no further abnormal measurements, whereas 247 had elevations on 2 or more readings, with a median highest level of 6.7 ng/mL. Of these 247 patients with confirmed false-positive CEA level elevations, only 5 (2%) had measurements greater than 15 ng/mL, and no confirmed elevation greater than 35 ng/mL was a false-positive,” the researchers reported.
The single isolated CEA elevations “were considered either transient false-positives from some acute process, or the result of simple laboratory or specimen labeling errors,” the researchers stated. The frequency of one-time false-positives and the finding that 93% of them were between 5.1 and 10.0 ng/mL “support a recommendation to repeat and confirm any abnormal CEA test results with measurements less than 10 ng/mL before embarking on further workup,” the investigators added.
False-positive results greater than 15 ng/mL were rare, and all confirmed levels greater than 35 ng/mL were associated with cancer recurrence. “Hence, CEA levels greater than 35 ng/mL seem to be virtually diagnostic of the presence of cancer,” the authors noted.
“This information is potentially useful for patients and doctors in terms of putting the meaning of the CEA elevation into context; the authors do not advocate initiation of chemotherapy or other therapeutic maneuvers based on an abnormal CEA level alone,” they wrote. “Recurrent disease should be identified based on diagnostic imaging studies and/or biopsy results before consideration is given to a therapeutic intervention.” ■
Litvak A, et al: J Natl Compr Canc Netw 12:907–913, 2014.