Carcinoembryonic antigen (CEA) testing may fail to detect disease recurrence in patients with rectal cancer who have negative CEA at baseline, according to research published in the Journal of the National Comprehensive Cancer Network.

The researchers noted that NCCN guidelines recommend the use of CEA testing in post-treatment surveillance for rectal cancer, and serial elevation of CEA is considered a strong marker of disease recurrence. 

However, there is “considerable heterogeneity” in CEA expression among patients with rectal cancer, the researchers wrote. In addition, evidence suggests that “approximately 70% of colorectal tumors consist largely of CEA-negative cell lines, and they are documented to have scarce or no CEA secretion.” 

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With this in mind, the researchers evaluated the diagnostic performance of serum CEA testing in 484 patients with stage I-III rectal cancer after curative resection. In this cohort, 350 patients were CEA negative at baseline, and 134 had elevated CEA. 

In the overall cohort, the median age was 58 (range, 50-68) years, 57.6% of patients were men, 59.3% had N0 stage disease, and 53.9% had moderate tumor differentiation.

The median follow-up was 52 months. Among patients in whom CEA levels were similar to those noted at baseline, 62.6% had any recurrence, 53.5% had a local recurrence, and 64.9% had a distant recurrence. 

Serum CEA testing had significantly lower sensitivity for detecting recurrence among patients with negative CEA at baseline than among those with elevated CEA at baseline — 41.3% and 69.4%, respectively (P =.007). This was true for distant (P =.005) and local recurrence (P =.048).

However, the researchers found that adding CA19-9 to the CEA assay improved sensitivity among patients with negative CEA at baseline. 

Compared with CEA testing alone, the CEA/CA19-9 assay increased the sensitivity for diagnosing overall recurrence (41.3% and 49.2%, respectively; P =.037) and distant recurrence (39.6% and 50.0%, respectively; P =.030). There was no significant difference for local recurrence, but the CEA/CA19-9 assay tended to be more sensitive.

“We recommend that the baseline CEA level should be considered and stratified before CEA can be applied in the surveillance protocol of the NCCN guidelines,” the researchers wrote. “Considering the insufficient sensitivity of CEA for recurrence surveillance in patients with negative baseline CEA, this subgroup of patients may obtain a survival benefit from the additional surveillance, including a CA19-9 assay, medical visit, and radiologic imaging.”


Shen D, Wang X, Wang H, et al. Current surveillance after treatment is not sufficient for patients with rectal cancer with negative baseline CEA. J Natl Compr Canc Netw. Published online March 1, 2022. doi:10.6004/jnccn.2021.7101