(ChemotherapyAdvisor) – Circulating tumor cells (CTCs) are a promising prognostic marker for patients with neuroendocrine tumors (NETs), “and should be assessed in the context of clinical trials with defined tumor subtypes and therapy,” the first prospective study to demonstrate this significance reported in the Journal of Clinical Oncology online December 17.

“The findings expand on those in other epithelial cancers and open the way for further evaluation of CTCs as liquid biopsies in this tumor type,” Tim Meyer, MD, PhD, UCL Cancer Institute, University College London, London, UK, and colleagues noted.

“Neuroendocrine tumors were thrust to the forefront of the oncology world last year with the much-heralded approval of two drugs, everolimus and sunitinib, for the treatment of advanced pancreatic neuroendocrine tumors,” an accompanying editorial noted.

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In addition, interest in CTCs as biomarkers has increased since U.S. Food and Drug Administration approval of CellSearch, a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells that can detect CTCs with high sensitivity, specificity, and reproducibility in small volumes of blood.

The investigators recruited 176 patients with measurable metastatic NETs between August 2009 and June 2011 and measured CTCs using CellSearch. After one sample was discarded due to hemolysis, 175 patients were evaluable.

“Overall, 49% patients had ≥ one CTC, 42% had two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood,” they reported. “Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA).”

The optimal prognostic threshold for progression-free survival (PFS) was defined as a cutoff of < one or ≥ one, with ≥ one CTC associated with worse PFS (hazard ratio [HR] 6.6; 95% CI 3.2-13.6; P<0.001) and overall survival (OS; HR 8.0; 95% CI 3.1-21; P<0.001).

When other prognostic markers, grade, tumor burden, and CgA were included in multivariate analysis, CTCs remained significant. Within grades, presence of CTCs was able to define a poor prognostic subgroup: grade 1 PFS, HR 5.0 (95% CI 1.3-18.5; P=0.017) and OS, HR 7.2 (95% CI 1.3-39.4; P=0.023); and grade 2, PFS, HR 3.5 (95% CI 1.2-10.1; P=0.018) and OS, HR 5.2 (95% CI 1.1-24; P=0.036).

“In this study, the number of CTCs detected in patients with NETs was comparable to other tumors in which CTCs have been shown to have prognostic relevance,” Dr. Meyer noted. “Overall, 42% of patients with NETs had ≥ two detectable CTCs, as compared with 57% for prostate, 37% for breast, 30% for colorectal, and 20% for non–small-cell lung cancers.

“In our study, the greatest number of patients had midgut (n=101) or pancreatic (n=42) tumors, and in these subgroups, 47% and 24%, respectively, had ≥ two CTCs detected. The reason for the high detection rate may be the high expression of EpCAM, which we and others have demonstrated in NETs.”