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Journal of Cancer Research and Clinical Oncology

, Volume 140, Issue 12, pp 2157–2162 | Cite as

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

  • Jasmin Loh
  • Lidija Jovanovic
  • Margot Lehman
  • Anne Capp
  • David Pryor
  • Monica Harris
  • Colleen Nelson
  • Jarad MartinEmail author
Original Article – Clinical Oncology

Abstract

Purpose

The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method.

Method

Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method.

Results

The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age.

Conclusion

This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

Keywords

Circulating tumor cells High-risk non-metastatic prostate cancer CellSearch® Biomarkers CTC 

Notes

Conflict of interest

We declare that we have no conflict of interest.

References

  1. Attard G et al (2009) Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res 69:2912–2918. doi: 10.1158/0008-5472.CAN-08-3667 PubMedCrossRefGoogle Scholar
  2. Bastian PJ et al (2007) Prognostic value of preoperative serum cell-free circulating DNA in men with prostate cancer undergoing radical prostatectomy. Clin Cancer Res 13:5361–5367. doi: 10.1158/1078-0432.CCR-06-2781 PubMedCrossRefGoogle Scholar
  3. Cohen SJ et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221. doi: 10.1200/JCO.2007.15.8923 PubMedCrossRefGoogle Scholar
  4. Cristofanilli M et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791. doi: 10.1056/NEJMoa040766 PubMedCrossRefGoogle Scholar
  5. Danila DC et al (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13:7053–7058. doi: 10.1158/1078-0432.CCR-07-1506 PubMedCrossRefGoogle Scholar
  6. Darshan MS et al (2011) Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res 71:6019–6029. doi: 10.1158/0008-5472.CAN-11-1417 PubMedCentralPubMedCrossRefGoogle Scholar
  7. Davis JW et al (2008) Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. J Urol 179:2187–2191. doi: 10.1016/j.juro.2008.01.102 discussion 2191PubMedCrossRefGoogle Scholar
  8. de Bono JS et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14:6302–6309. doi: 10.1158/1078-0432.CCR-08-0872 PubMedCrossRefGoogle Scholar
  9. Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I (2006) The detection of bone metastases in patients with high-risk prostate cancer: 99 mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 47:287–297PubMedGoogle Scholar
  10. Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626PubMedCrossRefGoogle Scholar
  11. Hou JM et al (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 30:525–532. doi: 10.1200/JCO.2010.33.3716 PubMedCrossRefGoogle Scholar
  12. Kats-Ugurlu G et al (2009) Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma. J Pathol 219:287–293. doi: 10.1002/path.2613 PubMedCrossRefGoogle Scholar
  13. Lecouvet FE et al (2012) Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer? Eur Urol 62:68–75. doi: 10.1016/j.eururo.2012.02.020 PubMedCrossRefGoogle Scholar
  14. Lilleby W, Stensvold A, Mills IG, Nesland JM (2013) Disseminated tumor cells and their prognostic significance in nonmetastatic prostate cancer patients. Int J Cancer 133:149–155. doi: 10.1002/ijc.28002 PubMedCrossRefGoogle Scholar
  15. Liotta LA, Saidel MG, Kleinerman J (1976) The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 36:889–894PubMedGoogle Scholar
  16. Ma X et al (2014) Prognostic role of circulating tumor cells and disseminated tumor cells in patients with prostate cancer: a systematic review and meta-analysis. Tumour Biol. doi: 10.1007/s13277-014-1731-5 Google Scholar
  17. Molnar B, Ladanyi A, Tanko L, Sreter L, Tulassay Z (2001) Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Cancer Res 7:4080–4085PubMedGoogle Scholar
  18. Resel Folkersma L, San Jose Manso L, Galante Romo I, Moreno Sierra J, Olivier Gomez C (2012) Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology 80:1328–1332. doi: 10.1016/j.urology.2012.09.001 PubMedCrossRefGoogle Scholar
  19. Schwarzenbach H, Alix-Panabieres C, Muller I, Letang N, Vendrell JP, Rebillard X, Pantel K (2009) Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer. Clin Cancer Res 15:1032–1038. doi: 10.1158/1078-0432.CCR-08-1910 PubMedCrossRefGoogle Scholar
  20. Selth LA et al (2013) Circulating microRNAs predict biochemical recurrence in prostate cancer patients. Br J Cancer 109:641–650. doi: 10.1038/bjc.2013.369 PubMedCentralPubMedCrossRefGoogle Scholar
  21. Spizzo G et al (2011) EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol 64:415–420. doi: 10.1136/jcp.2011.090274 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Stott SL et al (2010) Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med 2:25ra23. doi: 10.1126/scitranslmed.3000403 PubMedCentralPubMedCrossRefGoogle Scholar
  23. Thalgott M et al (2013) Detection of circulating tumor cells in different stages of prostate cancer. J Cancer Res Clin Oncol 139:755–763. doi: 10.1007/s00432-013-1377-5 PubMedCrossRefGoogle Scholar
  24. Wang MC, Valenzuela LA, Murphy GP, Chu TM (1979) Purification of a human prostate specific antigen. Invest Urol 17:159–163PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jasmin Loh
    • 1
  • Lidija Jovanovic
    • 2
  • Margot Lehman
    • 3
    • 4
  • Anne Capp
    • 1
  • David Pryor
    • 3
    • 4
  • Monica Harris
    • 1
  • Colleen Nelson
    • 2
  • Jarad Martin
    • 1
    Email author
  1. 1.Department of Radiation OncologyCalvary Mater NewcastleWaratahAustralia
  2. 2.Institute of Health and Biomedical InnovationQueensland University of TechnologyBrisbaneAustralia
  3. 3.Department of Radiation OncologyPrincess Alexandra HospitalBrisbaneAustralia
  4. 4.University of QueenslandBrisbaneAustralia

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