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The current role and future directions of circulating tumor cells and circulating tumor DNA in urothelial carcinoma of the bladder

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Abstract

Purpose

Urothelial carcinoma of the bladder (UCB) is clinically and genetically a highly heterogeneous disease. Treatment decisions are usually based on histopathological workup and molecular diagnostics on tissue biopsies of the primary tumor or the metastatic site. Next to completely different molecular genotypes of phenotypically similar tumors, standard biopsies do not unconditionally allow real-time insight during the natural course of disease progression. Indeed, in UCB there is an imperative need of biomarkers for improving clinical staging, detecting minimal residual disease, predicting therapy response and prognosis and finally enabling patient stratification for multimodal, individualized treatment and therapy monitoring.Liquid biopsies of blood-based circulating biomarkers have evolved from bench to bedside in some cancer entities.

Methods

In a narrative review we are summerizing the latest evidence on CTC and ctDNA in muscle-invasive and metastatic UCB.

Results

In this review, we summarize the current status, limitations and future needs of circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) in UCB. Moreover, we discuss the potential clinical application of CTC and ctDNA as prognostic markers at different UCB stages and their value for target therapy guidance.

Conclusions

CTC and ctDNA are promising circulating biomarkers in UCB, but none of both has progressed from bench to bedside yet. These markers may support outcome prognostication, patient counseling follow-up monitoring, and potentially decision-making regarding chemotherapy. Further prospective clinical or randomized studies are urgently warranted.

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Authors and Affiliations

  1. Department of Urology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Michael Rink & Armin Soave

  2. Institute of Tumor Biology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Heidi Schwarzenbach & Sabine Riethdorf

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  1. Michael Rink
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  2. Heidi Schwarzenbach
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  3. Sabine Riethdorf
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  4. Armin Soave
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MR: project development, data analysis, manuscript writing, and manuscript editing. HS: data collection, manuscript writing, and manuscript editing. SR: data collection, manuscript writing, and manuscript editing. AS: data collection, manuscript writing, and manuscript editing.

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Correspondence to Michael Rink.

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Dr. Michael Rink received honoraria by BMS and Pfizer. Dr. Michael Rink is investigator for the following companies and receives research grants by the following companies: Pfizer, MSD. All other authors have nothing to disclose.

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Rink, M., Schwarzenbach, H., Riethdorf, S. et al. The current role and future directions of circulating tumor cells and circulating tumor DNA in urothelial carcinoma of the bladder. World J Urol 37, 1785–1799 (2019). https://doi.org/10.1007/s00345-018-2543-9

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