An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

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Abstract

Objectives

With the advent of novel genomic and transcriptomic technologies, new urinary biomarkers have been identified and tested for bladder cancer (BCa) surveillance. To summarize the current status of urinary biomarkers for the detection of recurrence and/or progression in the follow-up of non-muscle invasive BCa patients, and to assess the value of urinary biomarkers in predicting response to intravesical Bacillus Calmette–Guerin (BCG) therapy.

Methods and materials

A medline/pubmed© literature search was performed. The performance of commercially available and investigational biomarkers has been reviewed. End points were cancer detection (recurrence), cancer progression, and response to BCG therapy.

Results

The performance requirements for biomarkers are variable according to the clinical scenario. The clinical role of urinary biomarkers in the follow-up of non-muscle invasive BCa patients remains undefined. The FDA-approved tests provide unsatisfactory sensitivity and specificity levels and their use is limited. Fluorescence in situ hybridization (FISH) has been shown to be useful in specific scenarios, mostly as a reflex test and in the setting of equivocal urinary cytology. FISH and immunocytology could conceivably be used to assess BCG response. Recently developed biomarkers have shown promising results; upcoming large trials will test their utility in specific clinical scenarios in a manner similar to a phased drug development strategy.

Conclusions

Current commercially available urinary biomarker-based tests are not sufficiently validated to be widely used in clinical practice. Several novel biomarkers are currently under investigation. Prospective multicenter analyses will be needed to establish their clinical relevance and value.

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Most cited references 99

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Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline.

Sam S Chang, Stephen A. Boorjian, Roger Chou … (2016)

Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients' rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC.

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The mechanism of action of BCG therapy for bladder cancer--a current perspective.

Gil Redelman-Sidi, Michael S Glickman, Bernard Bochner (2014)

Bacillus Calmette-Guérin (BCG) has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one of the most successful biotherapies for cancer in use. Despite long clinical experience with BCG, the mechanism of its therapeutic effect is still under investigation. Available evidence suggests that urothelial cells (including bladder cancer cells themselves) and cells of the immune system both have crucial roles in the therapeutic antitumour effect of BCG. The possible involvement of bladder cancer cells includes attachment and internalization of BCG, secretion of cytokines and chemokines, and presentation of BCG and/or cancer cell antigens to cells of the immune system. Immune system cell subsets that have potential roles in BCG therapy include CD4(+) and CD8(+) lymphocytes, natural killer cells, granulocytes, macrophages, and dendritic cells. Bladder cancer cells are killed through direct cytotoxicity by these cells, by secretion of soluble factors such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), and, to some degree, by the direct action of BCG. Several gaps still exist in our knowledge that should be addressed in future efforts to understand this biotherapy of cancer.

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Economic aspects of bladder cancer: what are the benefits and costs?

K-D Sievert, B. Amend, U. Nagele … (2009)

Objective Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care. Methods A PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC). Results New diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix®) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years. Conclusions The economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements.

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Author and article information

Contributors

Shahrokh F. Shariat: shahrokh.shariat@meduniwien.ac.at

Journal

Journal ID (nlm-ta): World J Urol

Journal ID (iso-abbrev): World J Urol

Title: World Journal of Urology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0724-4983

ISSN (Electronic): 1433-8726

Publication date (Electronic): 21 June 2018

Publication date PMC-release: 21 June 2018

Publication date (Print): 2018

Volume: 36

Issue: 12

Pages: 1981-1995

Affiliations

[1 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Department of Urology and Comprehensive Cancer Center, Vienna General Hospital, , Medical University of Vienna, ; Waehringer Guertel 18-20, 1090 Vienna, Austria

[2 ]Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy

[3 ]GRID grid.416167.3, Department of Urology, , The Mount Sinai Medical Center, ; New York, USA

[4 ]ISNI 0000 0000 9482 7121, GRID grid.267313.2, Department of Urology, , University of Texas Southwestern Medical Center, ; Dallas, USA

[5 ]ISNI 0000 0001 2175 4109, GRID grid.50550.35, Department of Urology, Hôpital Pitié-Salpétrière, , Assistance Publique—Hôpitaux de Paris Sorbonne Université, ; Paris, France

[6 ]ISNI 0000 0004 1937 116X, GRID grid.4491.8, Department of Urology, Hospital Motol, , Second Faculty of Medicine, Charles University, ; Prague, Czech Republic

[7 ]GRID grid.7080.f, Department of Urology, Fundació Puigvert, , Universidad Autónoma de Barcelona, ; Barcelona, Spain

[8 ]ISNI 000000041936877X, GRID grid.5386.8, Department of Urology, , Weill Cornell Medical College, ; New York, USA

[9 ]Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

Author information

Francesco Soria http://orcid.org/0000-0001-8443-8453

Article

Publisher ID: 2380

DOI: 10.1007/s00345-018-2380-x

PMC ID: 6280823

PubMed ID: 29931526

SO-VID: c7a4af87-5a77-4416-8e33-17eabc7d9267

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 11 April 2018

Date accepted : 15 June 2018

Custom metadata

ScienceOpen disciplines: Urology

Keywords: urinary biomarker,test,follow-up,surveillance,non-muscle invasive bladder cancer,recurrence

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ScienceOpen disciplines: Urology

Keywords: urinary biomarker, test, follow-up, surveillance, non-muscle invasive bladder cancer, recurrence

An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

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Abstract

Objectives

Methods and materials

Results

Conclusions

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Journal of Circulating Biomarkers

Most cited references 99

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline.

The mechanism of action of BCG therapy for bladder cancer--a current perspective.

Economic aspects of bladder cancer: what are the benefits and costs?

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