Skip to main content
Top
Published in: BMC Urology 1/2020

Open Access 01-12-2020 | Biomarkers | Research article

Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review

Authors: F. Lozano, C. X. Raventos, A. Carrion, E. Trilla, J. Morote

Published in: BMC Urology | Issue 1/2020

Login to get access

Abstract

Background

Genetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques.

Methods

Following PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported.

Results

There are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers.

Conclusions

Although cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.
Literature
4.
go back to reference Daneshmand S, Konety BR. American urological association (AUA) guideline American urological association non-muscle invasive bladder Cancer. AUA Clinical Guidelines, (April); 2016. p. 1–45. Daneshmand S, Konety BR. American urological association (AUA) guideline American urological association non-muscle invasive bladder Cancer. AUA Clinical Guidelines, (April); 2016. p. 1–45.
9.
go back to reference Kamat AM, Karakiewicz PI, Xylinas E, Hegarty PK, Hegarty N, Jenkins LC, et al. ICUD-EAU international consultation on bladder Cancer 2012: screening, diagnosis, and molecular markers. Eur Urol. 2012;63(2013):4–15.PubMed Kamat AM, Karakiewicz PI, Xylinas E, Hegarty PK, Hegarty N, Jenkins LC, et al. ICUD-EAU international consultation on bladder Cancer 2012: screening, diagnosis, and molecular markers. Eur Urol. 2012;63(2013):4–15.PubMed
11.
go back to reference Whiting, Penny F. ; Rutjes, Anne W.S.; Westwood, Marie E. ; Mallett, Susan ; Deeks, Jonathan J. ; Reitsma, Johannes B., ; Leeflang, Mariska M.G. ; Sterne, Jonathan A.C. ; Bossuyt, P. M. M. ; (2011). QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Internal Med Res RepMethods, 155(4), 529–536. Whiting, Penny F. ; Rutjes, Anne W.S.; Westwood, Marie E. ; Mallett, Susan ; Deeks, Jonathan J. ; Reitsma, Johannes B., ; Leeflang, Mariska M.G. ; Sterne, Jonathan A.C. ; Bossuyt, P. M. M. ; (2011). QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Internal Med Res RepMethods, 155(4), 529–536.
14.
go back to reference van der Aa MNM, Zwarthoff EC, Steyerberg EW, Boogaard MW, Nijsen Y, van der Keur KA, et al. Microsatellite analysis of voided-urine samples for surveillance of low-grade non-muscle-invasive Urothelial carcinoma: feasibility and clinical utility in a prospective multicenter study (cost-effectiveness of follow-up of urinary bladder Cancer trial C). Eur Urol. 2009;55(3):659–68. https://doi.org/10.1016/j.eururo.2008.05.001.CrossRefPubMed van der Aa MNM, Zwarthoff EC, Steyerberg EW, Boogaard MW, Nijsen Y, van der Keur KA, et al. Microsatellite analysis of voided-urine samples for surveillance of low-grade non-muscle-invasive Urothelial carcinoma: feasibility and clinical utility in a prospective multicenter study (cost-effectiveness of follow-up of urinary bladder Cancer trial C). Eur Urol. 2009;55(3):659–68. https://​doi.​org/​10.​1016/​j.​eururo.​2008.​05.​001.CrossRefPubMed
23.
go back to reference Roperch JP, Grandchamp B, Desgrandchamps F, Mongiat-Artus P, Ravery V, Ouzaid I, et al. Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. BMC Cancer. 2016;16(1):1–9. https://doi.org/10.1186/s12885-016-2748-5.CrossRef Roperch JP, Grandchamp B, Desgrandchamps F, Mongiat-Artus P, Ravery V, Ouzaid I, et al. Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. BMC Cancer. 2016;16(1):1–9. https://​doi.​org/​10.​1186/​s12885-016-2748-5.CrossRef
25.
28.
go back to reference Batista R, Vinagre J, Prazeres H, Sampaio C, Peralta P, Conceição P, et al. Validation of a novel, sensitive, and specific urine-based test for recurrence surveillance of patients with non-muscle-invasive bladder Cancer in a comprehensive multicenter study. Front Genet. 2019;10(December):1–15. https://doi.org/10.3389/fgene.2019.01237.CrossRef Batista R, Vinagre J, Prazeres H, Sampaio C, Peralta P, Conceição P, et al. Validation of a novel, sensitive, and specific urine-based test for recurrence surveillance of patients with non-muscle-invasive bladder Cancer in a comprehensive multicenter study. Front Genet. 2019;10(December):1–15. https://​doi.​org/​10.​3389/​fgene.​2019.​01237.CrossRef
43.
45.
go back to reference Renard I, Joniau S, van Cleynenbreugel B, Collette C, Naômé C, Vlassenbroeck I, et al. Identification and validation of the methylated TWIST1 and NID2 genes through Real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder Cancer in urine samples. Eur Urol. 2010;58(1):96–104. https://doi.org/10.1016/j.eururo.2009.07.041.CrossRefPubMed Renard I, Joniau S, van Cleynenbreugel B, Collette C, Naômé C, Vlassenbroeck I, et al. Identification and validation of the methylated TWIST1 and NID2 genes through Real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder Cancer in urine samples. Eur Urol. 2010;58(1):96–104. https://​doi.​org/​10.​1016/​j.​eururo.​2009.​07.​041.CrossRefPubMed
47.
go back to reference Billerey C, Chopin D, Bralet M, Lahaye J, Abbou CC, Bonaventure J, et al. Short Communication. 2001;158(6):1955–9. Billerey C, Chopin D, Bralet M, Lahaye J, Abbou CC, Bonaventure J, et al. Short Communication. 2001;158(6):1955–9.
50.
go back to reference Kiselev FL. MicroRNA and cancer. Mol Biol. 2014;48(2):232–42. Kiselev FL. MicroRNA and cancer. Mol Biol. 2014;48(2):232–42.
Metadata
Title
Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review
Authors
F. Lozano
C. X. Raventos
A. Carrion
E. Trilla
J. Morote
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Biomarkers
Published in
BMC Urology / Issue 1/2020
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-020-00670-x

Other articles of this Issue 1/2020

BMC Urology 1/2020 Go to the issue