Circulating tumor cells as prognostic markers in neuroendocrine tumors

J Clin Oncol. 2013 Jan 20;31(3):365-72. doi: 10.1200/JCO.2012.44.2905. Epub 2012 Dec 17.


Purpose: To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer.

Patients and methods: In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule-expressing cells.

Results: Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036).

Conclusion: CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Cell Separation
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / pathology*
  • Neuroendocrine Tumors / blood*
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology
  • Prognosis
  • Proportional Hazards Models
  • Young Adult


  • Biomarkers, Tumor