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Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer

Key Points

  • Circulating tumour cells (CTCs) have been validated as prognostic biomarkers of prostate cancer. These data have been generated with a number of different methods for CTC detection including the FDA-approved CellSearch test

  • Novel CTC assays have also been developed to help identify which prostate cancer patients are most likely to respond to androgen-pathway targeted therapies, such as abiraterone and enzalutamide

  • CTCs have also been studied as prognostic biomarkers of bladder cancer. These data have mostly been generated using the CellSearch test

  • One potential area of clinical application of CTCs in patients with urothelial carcinoma is the identification of patients with non-muscle-invasive bladder cancer who have been clinically understaged and are unlikely to benefit from intravesical therapy

  • CTCs have been less well studied as biomarkers of kidney cancer. This is related to the fact that renal cell carcinoma expresses low levels of EpCAM, a cell surface maker that is used by many CTC isolation methods

  • Alternative methods for CTC isolation that employ specific markers for kidney cancer have shown early promise

Abstract

Circulating tumour cells (CTCs) have been studied as biomarkers of a number of solid malignancies. Potential clinical applications for CTC analysis include early cancer detection, disease staging, monitoring for recurrence, prognostication, and to aid in the selection of therapy. In the field of urologic oncology, CTCs have been most widely studied as prognostic biomarkers of castration-resistant prostate cancer. Additionally, emerging data support a role for CTCs to help identify which patients are most likely to respond to novel androgen-pathway targeted therapies, such as abiraterone and enzalutamide. CTCs have also been studied as predictive biomarkers of bladder cancer, in particular as a means to identify patients whose disease has been clinically understaged. Less is known regarding CTCs in kidney cancer; this has been attributed to the fact that a minority of renal tumours express EpCAM, the epithelial cell surface protein commonly used by CTC assays for positive cell selection. However, alternative approaches using markers specific for kidney cancer are being explored.

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Figure 1: Schematic representation of CTCs entering the peripheral circulation and establishing a metastatic focus at a distant site.
Figure 2: Representative images of a CTC and WBC detected using the CellSearch test.
Figure 3: PC3 prostate cancer cells spiked into white blood cells.
Figure 4: Representative CTC subtypes detected by the Epic platform.

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M.A.G. and J.V. researched data for the article and wrote the manuscript. All authors made a substantial contribution to discussion of content and reviewed and edited the manuscript before submission.

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Correspondence to Michael A. Gorin.

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K.J.P. is a member of the advisory board to Celsee Diagnostics. The other authors declare no competing interests.

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Gorin, M., Verdone, J., van der Toom, E. et al. Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer. Nat Rev Urol 14, 90–97 (2017). https://doi.org/10.1038/nrurol.2016.224

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