Abstract
Purpose
To explore circulating tumor cell (CTCs) counts in different stages of prostate cancer (PC) in association with tumor burden, metastatic pattern and conventional serum biomarkers. Overall survival (OS) analyses were conducted with respect to optimized CTC cutoff levels.
Methods
Circulating tumor cell counts were assessed in healthy controls (n = 15) as well as in locally advanced high risk (LAPC, n = 20), metastatic castration resistant (mCRPC, n = 40) and taxane-refractory (mTRPC, n = 15) PC patients. CTCs were detected using the CellSearch™ System.
Results
In metastatic PC (mPC), CTC counts were significantly increased compared to LAPC (p < 0.001). In LAPC, CTCs were at control level (p = 0.66). Patients with both bone and visceral lesions revealed the highest median CTC count (p = 0.004), whereas patients with sole soft tissue metastases displayed CTC counts comparable to controls (p = 0.16). No correlation was observed between CTC counts and osseous tumor burden assessed by bone lesion count (p = 0.54) or bone scan index (p = 0.81). CTC counts revealed a positive correlation with alkaline phosphatase (p < 0.001) and lactate dehydrogenase (p < 0.001) as well as a negative association with hemoglobin (p = 0.004) and PSA-doubling time (p = 0.01). Kaplan–Meier analyses demonstrated a cohort adjusted cutoff level of 3 CTCs with a shorter OS in case of ≥3 CTCs compared to <3 CTCs (p = 0.001), a cutoff level applicable in mCRPC (p = 0.003) but not in mTRPC patients (p = 0.054).
Conclusions
Circulating tumor cell counts are applicable as a prognostic molecular marker, especially in mCRPC patients harboring bone metastases with or without visceral metastases. For clinical practice, mPC patients with elevated CTC counts in combination with short PSA-DT, high alkaline phosphatase and lactate dehydrogenase levels as well as low hemoglobin levels are at high risk of disease progression and limited OS.
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Acknowledgments
We thank Medistat GmbH, Kiel, Germany, for the statistical analyses. The work was supported by Sanofi-Aventis, Frankfurt, Germany, and scientific grants from Siegfried Gruber-Foundation, Munich, Germany.
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No actual or potential conflict of interest in relation to this article to declare.
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Mark Thalgott and Brigitte Rack contributed equally to this work.
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Thalgott, M., Rack, B., Maurer, T. et al. Detection of circulating tumor cells in different stages of prostate cancer. J Cancer Res Clin Oncol 139, 755–763 (2013). https://doi.org/10.1007/s00432-013-1377-5
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DOI: https://doi.org/10.1007/s00432-013-1377-5