Elevated postoperative serum carcinoembryonic antigen increased risk for recurrence, especially within the first 12 months after surgery, among patients with colon adenocarcinoma, according to a retrospective cohort analysis published in JAMA Oncology.
However, elevated preoperative carcinoembryonic antigen (CEA) that normalizes following resection did not predict poor prognosis, suggesting routine measurement of postoperative, and not preoperative CEA is warranted.
“Emphasis should be placed on postoperative CEA, and in the setting of modern high-quality imaging, we question the utility of measuring preoperative CEA,” Martin R. Weiser, MD, surgical oncologist in the colorectal service at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “Patients with elevated postoperative CEA tend to experience recurrence early, which might justify a risk-adjusted and individualized surveillance strategy.”
Guidelines recommend clinicians measure CEA levels preoperatively among patients with colon cancer. Although CEA levels that are persistently high after resection are associated with increased recurrence risk, the effect of levels that normalize is unknown.
Weiser and colleagues evaluated data from 1,027 patients (50.4% men; median age, 64 years) with stage I to stage III colon adenocarcinoma who underwent curative resection between 2007 and 2014.
After excluding patients without postoperative measurements, researchers divided patients into three cohorts: those with normal preoperative CEA (n = 715), those with elevated preoperative but normalized postoperative CEA (n = 142), and those with elevated preoperative and postoperative CEA (n = 57).
Three-year RFS served as the study’s primary endpoint.
During a median follow-up of 38 months, 94 patients (10.3%) had recurrences and 42 patients (4.6%) died. Three-year RFS for all patients was 88.4% (95% CI, 85.9-90.5).
Patients with normal preoperative CEA had a 3-year RFS of 89.7%, which was 7.4 percentage points higher than the 82.3% rate observed among the combined cohorts of patients with high preoperative levels (P = .01).
However, 3-year RFS did not significantly differ between the normal preoperative group and the normalized postoperative group alone (87.9%).
Patients with persistently elevated CEA levels showed a 3-year RFS 14.9 percentage points lower than the combined cohorts with normal postoperative CEA (74.5% vs. 89.4%; P = .001).
Multivariate analyses showed elevated postoperative CEA increased risk for recurrence (HR = 2; 95% CI, 1.1-3.5), whereas normalized postoperative CEA did not (HR = 0.77; 95% CI, 0.45-1.3).
Analyses of the smoothed curve of the hazard function showed recurrence risk appeared higher, and peaked earlier, in the elevated postoperative CEA group.
These results suggest the value of CEA as a biomarker is greatest as an early indicator of tumor recurrence, Rebecca Anne Miksad, MD, MPH, and Neal J. Meropol, MD, both employees of Flatiron Health, wrote in an accompany editorial.
The observation by Konishi and colleagues that the timing of recurrence is earlier among patients with elevated postoperative CEA introduces the concept of risk-stratified surveillance that varies based on overall risk and the timing of that risk,” they wrote. “While the term precision medicine is quite familiar in the setting of cancer treatment selection, its application to surveillance after definitive primary treatment also holds great promise if early subclinical metastasis can be identified and effectively treated with curative potential.” – by Alexandra Todak
Disclosures: Weiser and other study authors report no relevant financial disclosures. Miksad and Meropol report employment with Flatiron Health.