The role of circulating tumour cells and nucleic acids in blood for the detection of bladder cancer: A systematic review

Pramit Khetrapal; Matthew Wei Liang Lee; Wei Shen Tan; Liqin Dong; Patricia de Winter; Andrew Feber; John D Kelly

doi:10.1016/j.ctrv.2018.03.007

The role of circulating tumour cells and nucleic acids in blood for the detection of bladder cancer: A systematic review

Cancer Treat Rev. 2018 May:66:56-63. doi: 10.1016/j.ctrv.2018.03.007. Epub 2018 Apr 17.

Authors

Pramit Khetrapal¹, Matthew Wei Liang Lee², Wei Shen Tan³, Liqin Dong⁴, Patricia de Winter⁵, Andrew Feber⁴, John D Kelly³

Affiliations

¹ Division of Surgery and Interventional Science, University College London, 74 Huntley Street, London WC1E 6AU, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK. Electronic address: p.khetrapal@ucl.ac.uk.
² Fitzwilliam College, University of Cambridge, Storey's Way, Cambridge CB3 0DG, UK.
³ Division of Surgery and Interventional Science, University College London, 74 Huntley Street, London WC1E 6AU, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK.
⁴ UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
⁵ Division of Surgery and Interventional Science, University College London, 74 Huntley Street, London WC1E 6AU, UK.

PMID: 29684744
DOI: 10.1016/j.ctrv.2018.03.007

Abstract

Background: Blood-based biomarkers are a neglected resource in bladder cancer, where the mainstay of focus has been on urinary biomarkers. However, blood-based biomarkers are gaining popularity in other solid cancers, particularly circulating tumour cells (CTCs) and circulating nucleic acids. In this systematic review, we identify and discuss the diagnostic value of CTC, cell-free DNA and RNA based biomarkers in bladder cancer.

Methods: A MEDLINE/Pubmed systematic search was performed using the following keywords: (bladder cancer) AND (blood OR plasma OR serum) AND biomarker AND (DNA OR RNA OR cfDNA OR cell-free DNA OR RNA OR CTC). All studies including blood-based biomarkers based on DNA, RNA and CTCs were reviewed. Of the included studies, studies reporting sensitivity, specificity and/or AUC/ROC values were further described.

Results: Systematic searched yielded 47 studies that were eligible, of which 21, 19 and 3 studies reported DNA, RNA and CTC biomarkers respectively. 15 of these studies included sensitivity, specificity and/or AUC/ROC values. Biomarkers sensitivity and specificity ranged widely at 2.4-97.6% and 43.3-100% respectively. Median number of patients recruited in the studies was 56 (IQR 41-90). Only 3 studies included an independent validation cohort. The highest sensitivity and specificity pairing achieved in the validation cohort was 80.0% and 89.1% respectively.

Conclusions: This systematic review provides a comprehensive overview of the blood-based CTC and nucleic acid biomarkers that have been investigated. An overlap in interest of targets between studies suggests that these could be promising biomarkers, but few biomarkers achieve high sensitivity and specificity, and fewer still have been validated independently.

Keywords: Biomarker; Bladder cancer; CTCs; Cell-free DNA; Circulating tumor cells; Diagonostic; Liquid biopsy; RNA; cfDNA; miRNA.

Publication types

Review
Systematic Review

MeSH terms

Female
Humans
Male
Neoplastic Cells, Circulating / metabolism*
Neoplastic Cells, Circulating / pathology
Nucleic Acids / blood*
Urinary Bladder Neoplasms / diagnosis*
Urinary Bladder Neoplasms / pathology

Substances

Nucleic Acids