Skip to main content

Advertisement

Log in

Detection of circulating tumor cells in different stages of prostate cancer

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10(20):6897–6904

    Article  PubMed  Google Scholar 

  • Brawer MK, Benson MC, Bostwick DG, Djavan B, Lilja H, Semjonow A, Su S, Zhou Z (1999) Prostate-specific antigen and other serum markers: current concepts from the World Health Organization Second International Consultation on Prostate Cancer. Semin Urol Oncol 17(4):206–221

    PubMed  CAS  Google Scholar 

  • Chen BT, Loberg RD, Neeley CK, O’Hara SM, Gross S, Doyle G, Dunn RL, Kalikin LM, Pienta KJ (2005) Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease. Urology 65(3):616–621

    Article  PubMed  CAS  Google Scholar 

  • Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse MA, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, Meropol NJ (2009) Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol 20(7):1223–1229 [Epub 2009 Mar 12]

    Article  PubMed  CAS  Google Scholar 

  • Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430 Erratum in: J Clin Oncol (2005) Jul 20; 23(21):4808

    Article  PubMed  Google Scholar 

  • D’Amico AV, Chang E, Garnick M, Kantoff P, Jiroutek M, Tempany CM (1998) Assessment of prostate cancer volume using endorectal coil magnetic resonance imaging: a new predictor of tumor response to neoadjuvant androgen suppression therapy. Urology 51(2):287–292

    Article  PubMed  Google Scholar 

  • Danila DC, Heller G, Gignac GA, Gonzalez-Espinoza R, Anand A, Tanaka E, Lilja H, Schwartz L, Larson S, Fleisher M, Scher HI (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13(23):7053–7058

    Article  PubMed  CAS  Google Scholar 

  • Davis JW, Nakanishi H, Kumar VS, Bhadkamkar VA, McCormack R, Fritsche HA, Handy B, Gornet T, Babaian RJ (2008) Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. J Urol 179(6):2187–2191 Discussion 2191. [Epub 2008 Apr 18]

    Article  PubMed  Google Scholar 

  • De Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  Google Scholar 

  • Goodman OB Jr, Fink LM, Symanowski JT, Wong B, Grobaski B, Pomerantz D, Ma Y, Ward DC, Vogelzang NJ (2009) Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol Biomarkers Prev 18(6):1904–1913

    Article  PubMed  CAS  Google Scholar 

  • Graefen M, Karakiewicz PI, Cagiannos I, Quinn DI, Henshall SM, Grygiel JJ, Sutherland RL, Stricker PD, Klein E, Kupelian P, Skinner DG, Lieskovsky G, Bochner B, Huland H, Hammerer PG, Haese A, Erbersdobler A, Eastham JA, de Kernion J, Cangiano T, Schröder FH, Wildhagen MF, van der Kwast TH, Scardino PT, Kattan MW (2002) International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy. J Clin Oncol 20(15):3206–3212

    Article  PubMed  Google Scholar 

  • Heidenreich A, Bolla M, Joniau S, Mason MD, Matveev V, Mottet N, Schmid HP, van der Kwast TH, Wiegel T, Zattoni F (2010) Guidelines on prostate cancer. EAU guidelines, edition presented at the 25th EAU annual congress, Barcelona, 2010. ISBN 978-90-79754-70-0

  • Imbriaco M, Larson SM, Yeung HW, Mawlawi OR, Erdi Y, Venkatraman ES, Scher HI (1998) A new parameter for measuring metastatic bone involvement by prostate cancer: the bone scan index. Clin Cancer Res 4(7):1765–1772

    PubMed  CAS  Google Scholar 

  • Moreno JG, O’Hara SM, Gross S, Doyle G, Fritsche H, Gomella LG, Terstappen LW (2001) Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status. Urology 58(3):386–392

    Article  PubMed  CAS  Google Scholar 

  • Moreno JG, Miller MC, Gross S, Allard WJ, Gomella LG, Terstappen LW (2005) Circulating tumor cells predict survival in patients with metastatic prostate cancer. Urology 65(4):713–718

    Article  PubMed  Google Scholar 

  • Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239

    Article  PubMed  CAS  Google Scholar 

  • Okegawa T, Nutahara K, Higashihara E (2009) Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 181(3):1091–1097 [Epub 2009 Jan 16]

    Article  PubMed  Google Scholar 

  • Olmos D, Arkenau HT, Ang JE, Ledaki I, Attard G, Carden CP, Reid AH, A’Hern R, Fong PC, Oomen NB, Molife R, Dearnaley D, Parker C, Terstappen LW, de Bono JS (2009) Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience. Ann Oncol 20(1):27–33 [Epub 2008 Aug 11]

    Article  PubMed  CAS  Google Scholar 

  • Panteleakou Z, Lembessis P, Sourla A, Pissimissis N, Polyzos A, Deliveliotis C, Koutsilieris M (2009) Detection of circulating tumor cells in prostate cancer patients: methodological pitfalls and clinical relevance. Mol Med 15(3–4):101–114

    PubMed  CAS  Google Scholar 

  • Rink M, Chun FK, Minner S, Friedrich M, Mauermann O, Heinzer H, Huland H, Fisch M, Pantel K, Riethdorf S (2011) Detection of circulating tumour cells in peripheral blood of patients with advanced non-metastatic bladder cancer. BJU Int 107(10):1668–1675

    Article  PubMed  Google Scholar 

  • Rink M, Chun FK, Dahlem R, Soave A, Minner S, Hansen J, Stoupiec M, Coith C, Kluth LA, Ahyai SA, Friedrich MG, Shariat SF, Fisch M, Pantel K, Riethdorf S (2012) Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Eur Urol 61(4):810–817

    Article  PubMed  CAS  Google Scholar 

  • Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, Heller G (2009) Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 10(3):233–239

    Article  PubMed  CAS  Google Scholar 

  • Shaffer DR, Leversha MA, Danila DC, Lin O, Gonzalez-Espinoza R, Gu B, Anand A, Smith K, Maslak P, Doyle GV, Terstappen LW, Lilja H, Heller G, Fleisher M, Scher HI (2007) Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res 13(7):2023–2029

    Article  PubMed  CAS  Google Scholar 

  • Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E (1987) Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 317(15):909–916

    Article  PubMed  CAS  Google Scholar 

  • Sun YF, Yang XR, Zhou J, Qiu SJ, Fan J, Xu Y (2011) Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance. J Cancer Res Clin Oncol 137(8):1151–1173

    Article  PubMed  Google Scholar 

Download references

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.

Conflict of interest

  No actual or potential conflict of interest in relation to this article to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark Thalgott.

Additional information

Mark Thalgott and Brigitte Rack contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1377-5

Keywords

Navigation