Elevated preoperative carcinoembryonic antigen (CEA) that normalizes after colon cancer surgery is not an indicator of poor prognosis, researchers reported.
Although current guidelines recommend measuring preoperative CEA in patients with colon cancer, the investigators said that considering the results of their study, they now question the utility of that approach and think it would be wiser to emphasize postoperative CEA instead.
The study, by Tsuyoshi Konishi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues, was published in JAMA Oncology.
CEA is a colorectal cancer marker that the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the European Group on Tumour Markers all recommend be measured preoperatively in patients with nonmetastatic colon cancer.
For the study Konishi et al explained that the aim was to determine whether preoperative or postoperative CEA is more prognostic, and, more specifically, whether patients with elevated CEA that normalizes after resection have the same risk of recurrence as that of patients with normal preoperative CEA.
The retrospective cohort analysis included 1,027 patients (461 males, median age of 64) from a comprehensive cancer center who underwent curative resection for stages I to III colon adenocarcinoma between January 2007 and December 2014.
Preoperative CEA was normal in 715 patients (69.6%) and elevated in 312 (30.4%). Of the 312 with elevated preoperative CEA, 199 patients had postoperative CEA data available, and 142 of these had normalized postoperative CEA levels and 57 had elevated postoperative levels.
The patients were divided in three groups according to CEA status:
- Patients with normal (≤5.0 ng/mL) preoperative CEA (normal preoperative group)
- Patients with elevated (>5.0 ng/mL) preoperative CEA but normal postoperative CEA (normalized postoperative group)
- Patients whose preoperative and postoperative CEA levels were both elevated (elevated postoperative group)
Patients with normal preoperative CEA had a 7.4% higher 3-year recurrence-free survival (RFS) than the combined cohorts with elevated preoperative CEA, but had RFS comparable to that of patients with normalized postoperative CEA. Patients with elevated postoperative CEA had “significantly” lower 3-year RFS (14.9%) than the combined cohorts with normal postoperative CEA.
The hazard function for each group indicated that the risk of recurrence was higher and peaked earlier in patients in the elevated postoperative CEA group.
A univariate analysis showed that older age, the presence of lymphovascular invasion, higher tumor-nodes-metastasis (TNM) staging, and elevated postoperative CEA were all associated with shorter RFS.
Multivariate analyses showed that elevated postoperative CEA (HR, 2.0; 95% CI 1.1 to 3.5), was independently associated with shorter RFS as well as with higher TNM stage, older age, and presence of lymphovascular invasion, while normalized postoperative CEA (HR, 0.77; 95% CI 0.45 to 1.30) was not.
“These findings suggest that with regard to prognosis, measuring postoperative rather than preoperative CEA is more instructive,” the researchers concluded.
Elevated postoperative CEA often normalizes after surgery and these patients have outcomes similar to those of patients with normal preoperative CEA. As a result, the team wrote, emphasis should be placed on postoperative CEA. Furthermore, since patients with elevated postoperative CEA tend to experience recurrence early, risk-adjusted and individualized surveillance strategies should be considered.
Writing in an accompanying commentary, Rebecca Anne Miksad, MD, MPH, director of Gastrointestinal Oncology at Beth Israel Deaconess Medical Center in Boston, and Neal J. Meropol, MD, division chief of Hematology and Oncology at University Hospitals Cleveland Medical Center Case Comprehensive Cancer Center, said: “This study highlights the potential of real-world evidence to contribute insights that might ultimately lead to changes in clinical guidelines and standards of care.”
Miksad and Meropol noted that the weaknesses of the study — such as generalizability, potential selection biases, and inconsistency and attrition in follow-up — were typical for an observational study that included cohorts of patients from a single institution, but the results lay important groundwork for additional research. Furthermore, the editorial states, getting corroborative evidence from other real-world settings could justify changes in clinical practice recommendations without the need to go through a prospective randomized trial.
The research was funded in part by the National Institutes of Health/National Cancer Institute.
Konishi and co-authors reported having no conflicts of interest.
Miksad and Meropol reported being employees of Flatiron Health in New York City.
F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner