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Isolated, disseminated and circulating tumour cells in prostate cancer

Nature Reviews Urology volume 9, pages 448–463 (2012)Cite this article

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Abstract

The loss of single cells from a tumour cell cluster marks an early event in the metastatic process of cancer progression. Although the metastatic cascade in prostate cancer is yet to be fully understood, monitoring circulating tumour cells (CTCs) and quantifying the load of tumour cell dissemination is currently being implemented into routine clinical practice for diagnosing minimal residual disease (MRD), estimating prognosis and monitoring treatment success. Current methods for enrichment of CTCs or disseminated tumour cells (DTCs) and detection of MRD rely on the expression of specific marker genes or proteins that might be altered during the process of tumour cell dissemination, therefore disrupting tumour cell detection. The tumour origin and malignant potential for metastasis of marker-positive cells is not yet clear. Some studies have demonstrated the potential of CTCs or DTCs as prognostic or predictive markers, leading to the increasing implementation of CTC measurement as an end point in clinical trials.

Key Points

  • Systemic shedding of tumour cells marks an early event in tumorigenesis and is a prerequisite for distant recurrence after initial curative therapy

  • Evidence of minimal residual disease (MRD) is a negative prognosticator for prostate cancer

  • Current methods for the enrichment and detection of MRD rely on the expression of specific marker genes or proteins that might be altered during the process of tumour cell dissemination

  • Tumour origin and malignant potential for metastasis of marker-positive cells is not yet clear

  • Circulating and disseminated tumour cells have been reported as prognostic or predictive markers in prostate cancer leading to their increasing implementation as additional end points in clinical trials

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Figure 1: The metastatic cycle.
Figure 2: The compartment model.
Figure 3: Immunohistochemical detection and genomic characterization of isolated tumour cells.
Figure 4: Clinical relevance of MRD detection.

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Acknowledgements

The authors thank Miriam Germann for diligently reviewing and correcting the manuscript and Till Bechtold, Oliver Borst, Sascha Hoffmann and Kai Januschowski for fruitful discussions and valuable advice while preparing the manuscript.

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  1. Department of Urology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72016, Tübingen, Germany

    David Schilling, Tilman Todenhöfer, Jörg Hennenlotter, Christian Schwentner & Arnulf Stenzl

  2. Department of Gynaecology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72016, Tübingen, Germany

    Tanja Fehm

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  1. David Schilling
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D. Schilling and T. Todenhöfer contributed equally to researching data for the article, writing the article and reviewing the manuscript before submission. J. Hennenlotter provided a substantial contribution to researching data for the article, discussion of content and reviewing the manuscript before submission. C. Schwentner, T. Fehm and A. Stenzl provided substantial contributions to discussion of content and reviewing the manuscript before submission.

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Schilling, D., Todenhöfer, T., Hennenlotter, J. et al. Isolated, disseminated and circulating tumour cells in prostate cancer. Nat Rev Urol 9, 448–463 (2012). https://doi.org/10.1038/nrurol.2012.136

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