Prognostic significance of CEACAM5mRNA-positive circulating tumor cells in patients with metastatic colorectal cancer

Purpose To evaluate the clinical relevance of CEACAM5mRNA-positive circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). Methods Peripheral blood was obtained from 436 patients with mCRC before the initiation of systemic therapy. A second sample was obtained on treatment assessment from 296 (67.9%) patients. The detection of CEACAM5mRNA-positive CTCs was performed using a real-time PCR assay. Results The patients' median age was 67years and PS (EGOG 0-1) 92%; KRAS exon 2 and BRAF(V600E) mutated primary tumors were identified in 31.9% and 6.4% of the tested patients, respectively, whereas metastasectomy was performed in 17.7% of the patients. Circulating CEACAM5mRNA-positive CTCs were detected in 125 (28.7%) and 85 (28.7%) patients at baseline and on treatment assessment, respectively. The detection of CEACAM5mRNA-positive cells was revealed, in multivariate analysis, as an independent prognostic factor associated with decreased PFS (HR 1.6; 95% CI 1.1-2.5; p=0.026) and OS (HR 2.2; 95% CI 1.3-3.2; p<0.001). The detection of CEACAM5mRNA-positive CTCs in patients with KRAS and BRAF(V600E) mutations was correlated with shorter PFS (p=0.041 and p=0.022, respectively). Moreover, OS was significantly shorter in patients with CEACAM5+/KRAS mutations compared to those with CEACAM5+/KRAS wt tumors (p=0.023). Conclusions Detection of peripheral blood CEACAM5mRNA-positive CTCs is an adverse prognostic factor correlated with poor clinical outcome in patients with mCRC, especially in patients with KRAS and BRAF mutated tumors.