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Circulating tumour cells as a window into lethality in prostate cancer

Nature Reviews Urology (2026)Cite this article

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Abstract

Prostate cancer is characterized by multifocality, inter- and intra-patient tumour heterogeneity, and differences in risk of progression to metastatic disease, castration resistance and lethality, which can make prognosis challenging. Consequently, sampling methods that provide accurate insight into disease phenotype to facilitate risk-stratification of patients are crucial. The variable biology of prostate cancer seems to be recapitulated in the phenotypic heterogeneity of circulating tumour cells (CTCs). CTC sampling offers a liquid biopsy method to achieve minimally invasive longitudinal sampling for disease monitoring. CTC analysis has also offered a crucial insight into aggressive phenotypes, disease metastasis and treatment response, particularly in clinical trials. The clinical use of CTC count for prognosis in advanced prostate cancer has been approved by the FDA, but is not routinely used clinically, as these cells are technically challenging to isolate and analyse. However, methodological advances continue to improve CTC enrichment and profiling. Understanding the clinical utility of CTCs and future innovations is crucial to incorporating CTCs into the clinical management of prostate cancer.

Key points

  • Circulating tumour cells (CTCs) can be detected in blood from subsets of patients with prostate cancer by using antigen-dependent or -independent methods of enrichment.

  • New label-free enrichment strategies are renewing interest in CTCs after advances in next-generation sequencing had previously shifted the focus of liquid biopsy to cell-free DNA (cfDNA).

  • Molecular profiling of prostate cancer CTCs might offer a stratification tool for selecting patients for systemic therapy.

  • CTCs provide insight into the clinical and biological heterogeneity of prostate cancer, potentially offering markers of prognosis and/or treatment response.

  • Further study is needed on the role of CTCs in localized prostate cancer, requiring increased sensitivity and specificity of enrichment methods.

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Fig. 1: Isolation, detection and profiling workflow of circulating tumour cells.
Fig. 2: Current clinical utility for circulating tumour cell detection in localized and metastatic prostate cancer.

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Acknowledgements

S.M.A. would like to thank the Clarendon Fund in partnership with the St Edmund Hall Kerr-Muir Scholarship, specifically Mr. James Kerr-Muir, for their generous support. T.A. is funded by Cancer Research UK (RCCPDB-Nov23/100013) and supported by the National Institute for Health and Care Research (NIHR). I.G.M., C.M.E. and A.D.L. would like to acknowledge the John Black Charitable Foundation for support. C.M.E. would like to acknowledge support from Rosetrees. A.D.L. is funded by Cancer Research UK (C57899/A25812). Y.J.L. has received funding from Prostate Cancer UK (MA-CT20-011) to investigate the potential of using circulating tumour cells to predict prostate cancer surgical outcome. A.D.L. and R.J.B. are co-CIs of the TRANSLATE prostate biopsy trial funded by HTA (NIHR131233) and are module leads of the QUANTUM Biobank part funded by the John Black Charitable Foundation.

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Authors and Affiliations

  1. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, England, UK

    Sophia M. Abusamra, Thineskrishna Anbarasan, Nithesh M. S. Ranasinha, Sandy Figiel, Wencheng Yin, Freddie C. Hamdy, Richard J. Bryant, Ian G. Mills, Claire M. Edwards & Alastair D. Lamb

  2. Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England, UK

    Daniele T. Cotton & Claire M. Edwards

  3. Department of Inorganic Chemistry, University of Oxford, Oxford, England, UK

    Robert Barber & Jason J. Davis

  4. Bodleian Health Care Libraries, University of Oxford, Oxford, England, UK

    Suzannah Bridge & Carolyn Smith

  5. Department of Urologic Oncology, University of Michigan, Michigan Medicine, Ann Arbor, MI, USA

    Simpa S. Salami & Todd M. Morgan

  6. Barts Cancer Institute, Queen Mary University of London, London, England, UK

    Yong-Jie Lu & Alastair D. Lamb

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  1. Sophia M. Abusamra
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Contributions

S.M.A., T.A., D.T.C., N.M.S.R., S.B., C.S., A.D.L. researched data for the article. All authors contributed substantially to discussion of the content. S.M.A., T.A., D.T.C., N.M.S.R., R.B., S.F., W.Y., J.D., S.S., F.C.H., R.J.B., Y.J.L., I.M., C.M.E,. T.M.M., A.D.L. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Sophia M. Abusamra.

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S.M.A., C.M.E. and A.D.L. have received support from BioRad through the Celselect grant. T.M.M. is on the advisory boards for Merck, Foundation Medicine, Johnson & Johnson and Pfizer. A.D.L. has received educational support from GlaxoSmithKline, Astellas, Lilly, AstraZeneca and Ipsen. A.D.L. and F.C.H. have paid roles as BJUI Editors. Y.J.L. has received support from ANGLE PLC for his circulating tumour cell study. A.D.L. has received honoraria for reviewing for European Urology and Lancet Oncology. A.D.L. has received consulting fees from AlphaSights. A.D.L. undertakes medicolegal expert witness work related to prostate cancer management in the UK. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The other authors declare no competing interests.

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Abusamra, S.M., Anbarasan, T., Cotton, D.T. et al. Circulating tumour cells as a window into lethality in prostate cancer. Nat Rev Urol (2026). https://doi.org/10.1038/s41585-025-01121-8

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